The etiology of allergic rhinitis (AR) is complicated. Traditional therapy of AR still has challenges, such as low long-term treatment compliance, unsatisfactory therapeutic outcomes, and a high financial burden. It is urgent to investigate the pathophysiology of allergic rhinitis from different perspectives and explore brand-new possible preventative or treatment initiatives.The aim is to apply a multi-group technique and correlation analysis to explore more about the pathogenesis of AR from the perspectives of gut microbiota, fecal metabolites, and serum metabolism.Thirty BALB/c mice were randomly divided into the AR and Con(control) groups. A standardized Ovalbumin (OVA)-induced AR mouse model was established by intraperitoneal OVA injection followed by nasal excitation. We detected the serum IL-4, IL-5, and IgE by enzyme-linked immunosorbent assay (ELISA), evaluated the histological characteristics of the nasal tissues by the hematoxylin and eosin (H&E) staining, and observed the nasal symptoms (rubs and sneezes) to evaluate the reliability of the AR mouse model. The colonic NF-κB protein was detected by Western Blot, and the colonic histological characteristics were observed by the H&E staining to evaluate inflammation of colon tissue. We analyzed the V3 and V4 regions of the 16S ribosomal DNA (rDNA) gene from the feces (colon contents) through 16S rDNA sequencing technology. Untargeted metabolomics was used to examine fecal and serum samples to find differential metabolites. Finally, through comparison and correlation analysis of differential gut microbiota, fecal metabolites, and serum metabolites, we further explore the overall impact of AR on gut microbiota, fecal metabolites, and host serum metabolism and its correlation.Ruminococcus, were increased significantly in the AR group, while the other key differential genera, such as Lactobacillus, Bacteroides, and Prevotella, were significantly decreased in the Con group. Untargeted metabolomics analysis identified 28 upregulated and 4 downregulated differential metabolites in feces and 11 upregulated and 16 downregulated differential metabolites in serum under AR conditions. Interestingly, one of the significant difference metabolites, α-Linoleic acid (ALA), decreased consistently in feces and serum of AR. KEGG functional enrichment analysis and correlation analysis showed a close relationship between differential serum metabolites and fecal metabolites, and changes in fecal and serum metabolic patterns are associated with altered gut microbiota in AR. The NF-κB protein and inflammatory infiltration of the colon increased considerably in the AR group.In the AR group, the IL-4, IL-5, IgE, eosinophil infiltration, and the times of rubs and sneezes were significantly higher than those in the Con group, indicating the successful establishment of the AR model. No differences in diversity were detected between the AR and Con groups. However, there were modifications in the microbiota’s structure. At the phylum level, the proportion of Firmicutes and Proteobacteria in the AR group increased significantly, while the proportion of Bacteroides decreased significantly, and the ratio of Firmicutes/Bacteroides was higher. The key differential genera, such as Our study reveals that AR alters fecal and serum metabolomic signatures and gut microbiota characteristics, and there is a striking correlation between the three. The correlation analysis of the microbiome and metabolome provides a deeper understanding of AR’s pathogenesis, which may provide a theoretical basis for AR’s potential prevention and treatment strategies. AR seriMore and more evidence reveals that patients with allergic diseases have experienced gut microbiota dysbiosis, including asthma , food alHowever, gut microbiota analysis by 16S only explains the problem of “who is there”, and “what happened” needs further explanation from the fecal and serum metabolomics study. The multi-omics analysis of serum and feces has been widely used to explore the pathogenesis of allergic disease and even biomarkers . MetabolRuminococcus in the intestinal tract of AR mice. To our best knowledge, this is the first systematic analysis of the gut microbiota characteristics and metabolomic signatures of feces and serum in an AR mouse model. The alterations and correlations among the three will provide us with rich information about AR, gut microbiota, and host metabolism to explain how AR further affects mice’s fecal and serum metabolic signatures after affecting gut microbiota disturbance, which may provide a theoretical basis for the potential prevention and treatment strategies of AR.The population’s omics analysis can easily be affected by many factors such as diet, gender, and living habits, so we established a standardized animal model of AR and conducted multi-omics analysis on all of the mice’s feces and serum, combining 16S rDNA V3-V4 region sequencing for the investigation of the microbiome with LC-MS for the analysis of the fecal and serum metabonomic data. We analyzed how AR impacted the gut microbiota characteristics and metabolic patterns of feces and serum, after which we examined their relationships and involved pathways in more depth. Our study found that AR alters fecal and serum metabolomic signatures and gut microbiota characteristics, and changes in fecal and serum metabolic patterns are associated with altered gut microbiota in AR. Interestingly, we found that the intestinal and serum ALA of AR mice was significantly reduced, which may be related to the enrichment of 22.1ad libitum. All animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Fujian Medical University (IACUC number: FJMUIACUC2020-0106), and the animals’ care was provided following institutional guidelines.Specific pathogen-free (SPF) female BALB/c mice (4 weeks of age) were purchased from Shanghai Shrek experimental animals Co., Ltd. The animals are raised under specific pathogen-free conditions in the experimental animal center of Fujian Medical University, maintained on a 12-h daylight cycle and with free access to commercial pelleted food and water 2.2According to previous literature, the OVA-alum AR model was established . Thirty 2.3After the last intranasal allergen challenge on day 28, the times of sneezes and rubs were counted for 15 minutes to evaluate allergic responses by blinded observers .2.4Samples of blood, colon contents, nasal mucosa, and colon mucosa were prepared 24 h after the last OVA nasal challenge. Blood was drawn from the ophthalmic artery, and serum was extracted by centrifugation at 4000 rpm (4°C for 10 minutes) and stored at -80°C. For the first time after mouse sacrifice, we cut off the colon specimen in the sterile operation, collected the feces (colon contents) in the sterile tube, and stored it at -80°C. The muscle tissue of the nose was removed, and the nasal cavity was fixed with 4% formaldehyde solution for 24 h at 37°C.2.5Serum levels of IgE , IL-4 , and IL-5 in Con and AR groups were measured by ELISA kits, according to the manufacturer’s instructions. The absorbance was measured in a microplate reader at 450 nm. Triple pore detection was used to calculate the mean values.2.6The fixed nasal tissue was decalcified with a JYBL-I de-calcification solution . After 24 h, the nasal and colonic tissues were embedded in paraffin and cut into conventional sections at 4 μm. The sections (4-µm) were dewaxed, stained with hematoxylin  for 10 min, differentiated with 1% hydrochloric acid ethanol for 1 min, stained with eosin for 1 min, dehydrated with a series of ethanol concentrations  ethanol for 10 sec, incubated with xylene for 1 min and sealed. In addition, other sections were dewaxed, soaked with 3% acetic acid for 3 min, stained with 1% Alcian blue  for 30 min, soaked with 3% acetic acid for 3 min, washed with water, oxidized with 0.5% periodate for 10 min, soaked in Schiff’s solution for 20 min and sealed.2.7The radioimmunoprecipitation assay (RIPA) buffer contains 25 mM Tris HCl (pH 7.2), 0.15M NaCl, 0.1% SDS, 1% Triton X-100, 1% sodium deoxycholate, and 1mM EDTA, was used to make tissue lysates. A bicinchoninic acid protein assay kit was applied to determine the protein content (Pierce). Proteins were transferred to a nitrocellulose membrane after being electrophoresed on sodium dodecyl sulfate-polyacrylamide gel. After blocking, a goat polyclonal antibody directed against a rabbit or mouse was used to identify total protein or phosphorylation. Using digital imaging equipment, protein bands were measured (UVtec).2.8Stool samples were diluted in water, ultrasonically mixed, and centrifuged at 14,000 rpm and 4°C for 20 min. The supernatant (0.5 ml), anhydrous sodium sulfate (0.3 g), 50% sulfate acid  were added into a 4 mL Eppendorf tube and vortex-mixed. The mixture was centrifuged at 4,000 rpm and 4°C for 20 min. The serum samples (100 μl) were treated with methanol (200 μl), mixed, and centrifuged at 14,000 rpm and 4°C for 15 min. The supernatant was then analyzed by Ultra-High-Performance Liquid Chromatography-Tandem Time of Flight mass spectrometry (UPLC-Q-TOF/MS) to determine metabolites in the feces and serum.2.9®High-Fidelity PCR Master Mix (New England Biolabs), 0.2μM of forward and reverse primers, and about 10 ng template DNA. Thermal cycling consisted of initial denaturation at 98°C for 1 min, followed by 30 cycles of denaturation at 98°C for 10 s, annealing at 50°C for 30 s, and elongation at 72°C for 60 s. Finally, 72°C for 5 min. After PCR amplification, the mixture of PCR products was purified with AxyPrepDNA Gel Extraction Kit (AXYGEN). Following the manufacturer’s recommendations, sequencing libraries were generated using NEB Next®Ultra™DNA Library Prep Kit for Illumina . Index codes were added, and the library was sequenced on an Illumina Miseq/HiSeq2500 platform, generating 250/300 bp paired-end reads. More detailed experimental steps and the analysis of the metagenomic data are described in supporting information. Sequence data associated with this project have been deposited in the NCBI Short Read Archive database (Accession Number: PRJNA948919).16S rDNA high-throughput sequencing is an important method to study the composition and structure of the microbial community in the intestine by designing universal primers for PCR amplification using conserved regions and then sequencing analysis and strain identification of hypervariable regions. Total genome DNA was extracted from fecal samples using the CTAB/SDS method. 16S rDNA was amplified using a library of barcode-linked primers. The V3-4 hypervariable bacterial 16S rRNA gene region was amplified with the universal primer 338F (5’-ACTCCTACGGGAGGCAGCAG-3’) and 806R (5’-GGACTCANNGGGTA TCTAAT-3’). All PCR reactions were carried out in 30μl reactions with 15μl of Phusion2.10t-test and Wilcox’s test were used for comparison between groups. Correlation analysis was evaluated using a Spearman correlation analysis. P value < 0.05 was considered statistically significant. Analyses were performed using SPSS version 25.0, R(v3.6.0), and Python(v2.7).The data are expressed as mean ± SD. The 33.1Two mice in the AR group died of abdominal infection during the experiment, and the sneezes and rubs of the remaining 13 mice in the AR group were significantly higher than that in the Con group  analysis is a linear discriminant analysis (LDA) of samples according to different grouping conditions and taxonomic compositions to determine the communities or species that express significant differences in sample division . LEfSe a3.3P value <0.05 in OPLS-DA analysis were further analyzed.Considering the distinct composition of gut microbiota between the AR and Con groups, we further performed metabolomics of fecal and serum samples from mice using UPLC-Q-TOF/MS in negative ion mode (ES-). The serum and feces metabolomic signatures were remarkably separated from the Con group in Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) score plots , and D-Mannose, were significantly reduced in the AR group. In contrast, 11 serum differential metabolites, such as Taurochenodeoxycholate (TCDCA), Cholic acid, Deoxycholic acid, Urocanic acid (UCA), 3-Phenylpropanoic acid, and L-Tryptophan, were increased significantly in the AR group. We listed the Log2FC, P-value, and VIP values of the serum differential metabolites in AR disrupts the serum metabolome. We ultimately identified 27 differential metabolites, with the changing trend illustrated by the histogram  is a tool for predicting bacterial community function based on species , and we 3.6A recent study  revealedBased on the current discussion on the pathogenesis of AR, clinical treatment for AR includes environmental control, drug treatment, immunotherapy, and surgical intervention . HoweverOur study showed that AR alters gut microbiota composition. The proportion of the phyla Firmicutes in the AR group was higher, while the phyla Bacteroidetes significantly decreased in AR, consistent with a recent study about AR adult patients and mice . Many BaRuminococcus, which is comparable to the results of previous studies , the essential fatty acid that humans should obtain from their diet. More and more evidence shows that ALA can inhibit inflammation and be beneficial in various inflammation-related diseases, such as inflammatory bowel disease, rheumatoid arthritis, and asthma . Under dRuminococcus, have multiple interactions with key differential fecal metabolites. Our study found that Ruminococcus negatively correlated with ALA and Arachidonic acid. Interestingly, ALA in serum and feces decreased consistently. More and more evidence shows a correlation between ALA and gut microbiota (Ruminococcus), resulting in decreased ALA in the gut and serum. In return, the decreased fecal and serum ALA may also aggravate the host immune imbalance, which may be due to the change of intestinal mucosal immune state under the allergic inflammatory state of the host  can be found below: The animal study was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of Fujian Medical University.ZC and SH designed the project, performed the experiment, drafted the manuscript, and they contributed equally. YL, YWe, CC, and QX performed the experiment and collected the study data. YL and YWa analyzed the data. LL and YX conceived the study, got administrative support, and they contributed equally. All authors contributed to the article and approved the submitted version.


Neuromotor rehabilitation and improvement of upper limb functions are necessary to improve the life quality of patients who have experienced injuries or have pathological outcomes. Modern approaches, such as robotic-assisted rehabilitation can help to improve rehabilitation processes and thus improve upper limb functions. Therefore, the aim of this study was to investigate the role of robots in upper limb disability improvement and rehabilitation.This scoping review was conducted by search in PubMed, Web of Science, Scopus, and IEEE (January 2012– February 2022). Articles related to upper limb rehabilitation robots were selected. The methodological quality of all the included studies will be appraised using the Mixed Methods Appraisal Tool (MMAT). We used an 18-field data extraction form to extract data from articles and extracted the information such as study year, country, type of study, purpose, illness or accident leading to disability, level of disability, assistive technologies, number of participants in the study, sex, age, rehabilitated part of the upper limb using a robot, duration and frequency of treatment, methods of performing rehabilitation exercises, type of evaluation, number of participants in the evaluation process, duration of intervention, study outcomes, and study conclusions. The selection of articles and data extraction was made by three authors based on inclusion and exclusion criteria. Disagreements were resolved through consultation with the fifth author. Inclusion criteria were articles involving upper limb rehabilitation robots, articles about upper limb disability caused by any illness or injury, and articles published in English. Also, articles involving other than upper limb rehabilitation robots, robots related to rehabilitation of diseases other than upper limb, systematic reviews, reviews, and meta-analyses, books, book chapters, letters to the editor, and conference papers were also excluded. Descriptive statistics methods (frequency and percentage) were used to analyses the data.We finally included 55 relevant articles. Most of the studies were done in Italy (33.82%). Most robots were used to rehabilitate stroke patients (80%). About 60.52% of the studies used games and virtual reality rehabilitate the upper limb disabilities using robots. Among the 14 types of applied evaluation methods, “evaluation and measurement of upper limb function and dexterity” was the most applied evaluation method. “Improvement in musculoskeletal functions”, “no adverse effect on patients”, and “Safe and reliable treatment” were the most cited outcomes, respectively.Our findings show that robots can improve musculoskeletal functions  and empower people by providing a variety of rehabilitation capabilities.The online version contains supplementary material available at 10.1186/s13690-023-01100-8. Impaired upper limb (UL) functions to restrict the performance of activities of daily living, limit social participation , specifiNeuromotor rehabilitation and recovery of upper extremity functions are necessary to improve the life quality of individuals who have suffered injuries, disabilities or have pathological outcomes, where it is favorable to raise the development of activities of daily living . HoweverNew therapeutic methods have been presented to rehabilitate and improve upper limb function, and such methods are robotic rehabilitation . Severe Therefore, multiple benefits can be considered for rehabilitation robots : they can produce high-quality repetitive movements and increase rehabilitation strength and intensity; they can offer many types of exercises for therapists to choose from; they supply a man-machine interaction that allows for objective measurement of advancement, which itself can status modifications in interaction by changing control parameters . On the Robots can also be used in homes, clinics and medical centers. Patients can do the rehabilitation exercises prescribed by the therapist with the help of the robot at home without having to visit the treatment center frequently. Successful robot-assisted rehabilitation at home can facilitate intensive therapy, facilitate in-person or virtual therapy visits, preferably at low cost, and motivate patients to participate in supervised or unsupervised therapeutic activities at necessary levels for motor learning and generalization to occur . MoreoveTo our knowledge, no systematic or scoping review has been performed on robots to rehabilitate upper limb disabilities. Only a few systematic reviews have been done in the areas of classification of interactive wearable systems for monitoring body movement and posture during upper body rehabilitation, estimating the wearability of the wearable devices , presentIn the current study, we used the PRISMA scoping reviews checklist for selecting studies and reporting the results .To find articles related to the rehabilitation of upper limb disabilities using robots, four databases, PubMed, Web of Science, Scopus, and IEEE were searched. In order to search these databases, the keywords related to the upper limb, rehabilitation, and robots were used. Relevant Medical Subject Heading (MeSH) Keywords, spelling differences and synonyms were included and altered as suitable for each database. Then, the below search strategy was developed by KB, ASH, and KHM and finally approved by AH.((upper extremity disability OR upper limb disability) AND (rehabilitation OR telerehabilitation) AND (robot OR robotics))Articles addressing upper limb rehabilitation robots were included in to study. The PRISMA diagram is demonstrated in Fig. Inclusion and exclusion criteria are presented below.Articles involving upper limb rehabilitation robots.Articles about upper limb disability caused by any illness or injury.Studies involving rehabilitation robots designed for all ages.Robotic devices used with any assistive technologies Articles published in English.Time of publication between January 2012– February 2022.It should be noted due to the rapid development of technologies and rehabilitation robots, we limited our investigation to the last ten years. We wanted to identify the latest and newest technologies that can be used along with rehabilitation robots, evaluation methods and the outcomes of these robots in recent years. Xue et al. , believeArticles involving other than upper limb rehabilitation robots.Robots related to rehabilitation of diseases other than upper limb.Systematic reviews, reviews, and meta-analysis.Books.Book chapters.Letter to the editor.Conference abstracts.Research protocol or protocol study.First, abstracts of all related articles were retrieved from four databases: PubMed, Web of Science, Scopus, and IEEE, and imported into EndNote software by KHM. Duplicate articles were removed. After studying the title, and abstract, the relevant articles were selected according to the inclusion and exclusion criteria by KHM and ASH. Then, all studies included in the study were reviewed and finalized by KB and AH. In disagreement, the final decision on each article is decided by discussion among the study team members. Finally, the full text of the articles was studied to extract data and information from KHM and ASH.Critical evaluation of data was done by ASH and KHM independently using Mixed Methods Appraisal Tool . Disagreement between authors (n = 4 articles) was resolved by discussion between two other authors (KB and AH) until reaching an agreement. We evaluated studies according to the MMAT criteria according to the selected category. The latest version of the MMAT offers a descriptive quality appraisal instead of a summative numerical score. Answer options in all study categories include “yes”, “no” and “can’t tell”. The answer “can’t tell” indicates that not enough information was reported in the study for a “yes” or “no” answer. A “can’t tell” rating may indicate a need to search for companion studies or contact study authors for more information .Data were extracted using a predetermined form. The validity of this form was confirmed by two specialists in medical informatics and software engineer, a physiotherapist, and a specialist in health information management. This data extraction form also includes fields such as year, country, type of study, purpose, illness or accident leading to disability Table , level oThe information extracted from the articles was re-examined by KB and finally approved by AH. In case of disagreement, the consensus was achieved by the review of the members of the study team. It should be noted that for articles with missing data and information, we emailed the corresponding author and asked them to send us the necessary information. Finally, two authors extracted all data from eligible full-text documents through Excel.After the data were stored and managed in MS Excel for processing, to synthesize data, one author (KHM) checks all imported data . Then, descriptive statistics (frequency and percentage) were used to summarize the collected data. Descriptive data obtained from the findings of the included articles were organized into tables and figures based on themes to present the findings of this review, which guided the study aims by .The protocol of this study was approved by the ethical committee of Kerman University of Medical Sciences) IR.KMU.REC.1400.606).From the 348 non-duplicate articles found using the search strategy, 55 articles were selected for inclusion Fig. . SummariThe findings of the quality assessment of studies based on MMAT are presented in Appendix Most of the studies were done in Italy n = 19, 34.55%) , 76, 79.9, 34.55%As shown in Fig. Robots were used to rehabilitate seven categories of diseases or complications leading to upper limb disability Fig. . Most roEight different levels of upper limb disability were identified Table . The higTable Use of telerehabilitation and virtual reality in robots.60.52% of the studies used games and virtual reality to rehabilitate the upper extremities in robots –73, 75 , 73, 75.According to Tables The most important outcomes of upper limb rehabilitation robots were “Improvement in musculoskeletal functions”, “No adverse effect on patients”, and “Safe and reliable treatment”, respectively. Other outcomes are listed in Table In this scoping review, outcomes of rehabilitation robots for upper limb disabilities and different methods for evaluating rehabilitation robots were identified. Most robots were used for the rehabilitation of patients with stroke. Along with robots, telerehabilitation and virtual reality, technologies were also used for upper limb disabilities rehabilitation. “Evaluation and measurement of upper limb function and dexterity” was the most common type of evaluation among the 14 types performed for upper limb rehabilitation robots. Also, we identified different outcomes of using rehabilitation robots for upper limb disabilities.As discussed above, telerehabilitation and virtual reality were two types of technology used along with rehabilitation robots. Some studies , 82, 83 The findings of this study and other reviews , 88, 89 Additionally, the exoskeleton robot’s high inertia to its complex structure can intervene with manipulation. Or, in the mechanical dimensions of the robot, the degree of freedom should be considered an important factor in the design. For example, intervention with six degrees of freedom in a three-dimensional space is very challenging for stroke patients with moderate to severe motor impairment . The terAlthough, in this review we observed that rehabilitation robots have no adverse effect on patients, in some studies, the complications of rehabilitation robots have been mentioned . BesslerBesides, we should be able to improve the design, development and evaluation of rehabilitation robots so that they have the necessary quality to provide rehabilitation services. Abu-Dakka et al.  believedAccordingly, a patient who perceives a device as usable is likely also report a positive perception as a concern: ease of learning the system’s function and behavior, effort expended to reach a goal, ease of remembering the system’s performance for any further use, the system’s ability to easily support and recover the case of errors during use and the pleasant design of the system. Thus, assessing such aspects provides important insights into the acceptability and perceived usefulness of devices, thereby allowing an understanding of how to improve patient motivation during treatment. As emphasized in Monardo’s study , motivatAccording to the findings of the studies, we found that robots were a safe and reliable treatment for patients. Therefore, it is necessary to consider a set of factors for the rehabilitation robot to guarantee patient safety and maintain its reliability for patients. Sampson et al. , evaluatReduction or relief of pain was another outcome of this review. Some studies , 95 haveDuration and intensity of the therapy through the robot are two other factors that effect on the robots in motor control and improving pains. By examining the effectiveness of robots on function and structure in patients with limited upper limb function, Ferreira et al.,  showed tAs our study showed, robots can increase patients’ interest and motivation to perform rehabilitation exercises. Therefore, one of the other factors that can be considered to increase patients’ use of robots and their interest and motivation to perform rehabilitation exercises is the use of games and virtual reality. Creating a degree of entertainment through games and virtual reality can improve patients’ adherence to rehabilitation exercises and increase patients’ attention span to spend more time on their rehabilitation program . Kafri eEfficiency and effectiveness of rehabilitation robots, increasing the patient’s independence in performing rehabilitation exercises, rehabilitation robots’ feasibility for training patients, performing repetitive and long exercises very easily with the help of the robot, reducing the duration of rehabilitation exercises, increasing adherence to rehabilitation exercises and more participation in treatment processes, and improving quality of life and rehabilitation process were other outcomes related to rehabilitation robots identified in this study. But it must be said that these outcomes or other mentioned outcomes will not be created spontaneously due to the use of rehabilitation robots, but a series of main factors or capabilities must be included in the robots so that these outcomes can be created and have a and beneficial effect in rehabilitation. For example, Laut et al.  believedIn other words, changing from a hospital to a home rehabilitation program can reduce costs while making rehabilitation more accessible . FrancisIn addition, concerning adherence to rehabilitation exercises, it can be said that considering technologies such as sensors and computer game technologies for home rehabilitation or mRehab (mobile rehabilitation) systems in robots greatly increases the possibility of objective quantification of adherence . Also, fIn general, it can be said that although the findings of the present study showed that rehabilitation robots could lead to positive outcomes for people with upper limb disabilities with various diseases or injuries, but if the factors that lead to these outcomes in If these robots are not considered, they will never have the necessary efficiency, effectiveness and quality.It is predictable that rehabilitation robots will be applied much more than before in an era where the cost of manual therapy is becoming more expensive. To better popularize and commercialize this goal, future development needs to increase the universality of rehabilitation robots, focusing on portable, lightweight, reconfigurable, smart, and equipment based on artificial intelligence and machine learning techniques, new methods of treatment and thinking to the field of rehabilitation under the hypothesis of guaranteeing safety, mass production and development in a cheap direction . For exaMoreover, in the future, there should be more focus on “human nature” in the design and development of rehabilitation robots. Human nature means that robots have capabilities such as “perception, thinking, action and cooperation, expression and communication, and learning and adaptability and complete training and operations independently or with the assistance of an automatic machine” . At presThere are a few limitations in this study. In the present study, only articles in English were reviewed; it is better to include articles published in non-English languages in future studies. Also, to find related studies, we searched four databases, Scopus, IEEE, PubMed, and Web of Science. It is suggested that more studies be done in more databases to obtain more comprehensive results.This scoping review indicates that upper limb rehabilitation robots can improve musculoskeletal functions ; avoid serious side effects or adverse effects on the patient, provide safe and reliable treatment, reduce pain, increase the patient’s independence in performing rehabilitation exercises, reduce the duration of rehabilitation exercises, increase adherence to rehabilitation exercises and treatment processes, and quality of life and rehabilitation processes. The use of rehabilitation robots is growing strongly, especially in developed countries, and it seems that this new rehabilitation technology has had significant effects in helping to improve upper limb disabilities.Also, rehabilitation robots could provide a platform for motivating people with upper limb disabilities to carry out more rehabilitation exercises without a therapist, which could maximize recovery.Below is the link to the electronic supplementary material.Supplementary Material 1 Aims and scope statementSupplementary Material 2: Appendix ASupplementary Material 3: Appendix BSupplementary Material 4: Appendix C


The as-prepared carbodithioate derivative 3 is considered to be a key molecule for the preparation of new antipyrine-1,3,4-thiadiazole-based molecules (4–9) through its reaction with the appropriate hydrazonoyl halides. Furthermore, a typical Biginelli three-component cyclocondensation reaction involving ethyl acetoacetate, 4-antipyrinecarboxaldhyde, and thiourea under the standard conditions is carried out in the presence of sulfuric acid to afford the corresponding antipyrine–pyrimidine hybrid molecule (10). The latter was submitted to react with hydrazine monohydrate to provide the corresponding hydrazide derivative (11) which, under reaction with ethyl acetoacetate in refluxing ethanol containing catalytic amount of acetic acid, afforded the corresponding derivative (12). The structure of the newly synthesized compounds was affirmed by their spectral and microanalytical data. We also screened for their antimicrobial potential (ZOI and MIC) and conducted a kinetic study. Additionally, the mechanism of biological action was assessed by a membrane leakage assay and SEM imaging technique. Moreover, the biological activities and the binding modes of these compounds were further supplemented by an in silico docking study against E. coli β-carbonic anhydrase. The amount of cellular protein released by E. coli is directly correlated to the concentration of compound 9, which was found to be 177.99 µg/mL following treatment with 1.0 mg/mL of compound 9. This finding supports compound 9’s antibacterial properties and explains how the formation of holes in the E. coli cell membrane results in the release of proteins from the cytoplasm. The newly synthesized compounds represent acceptable antimicrobial activities with potential action against E. coli β-carbonic anhydrase. The docking studies and antimicrobial activity test proved that compound (9) declared a greater activity than the other synthesized compounds.In this investigation, 4-antipyrinecarboxaldhyde was reacted with methyl hydrazinecarbodithioate to afford the carbodithioate derivative  Antipyrine-based molecules continue to be of great interest for both medicinal chemists and organic chemists owing to their richness in synthetic compounds with multifarious involvement in pharmaceutical and medicinal compounds ,2. In thOn the other hand, 1,3,4-thiadiazoles ,15,16,17E. coli, particularly among immunocompromised individuals utilizing urethral and intravascular catheters  at m/z = 498 in an approximate ratio of 1:1, which supported the molecular formula (C23H21ClN6O3S).4-antipyrinecarboxaldhyde (oate (3) . We wereperature . The che1), and thiourea to afford the desired molecule 10. In the reaction performed via the tetrahedral mechanism, in which the N-C bond was formed first and then the C-O bond begin to break, the elimination of ethanol occurred, and so a lot of energy was accumulated in the medium of the reaction to offset the activation energy of the reaction, and a conversion took place, followed by cyclization via the nucleophilic attack through the amine group onto the carbonyl group to give the target molecule 10. Compound 10 was reacted with hydrazine hydrate to yield the corresponding hydrazide derivative 11, which then reacted with ethyl acetoacetate in ethanol containing a catalytic amount of acetic acid to afford the corresponding pyrazole derivative 12 [12 was confirmed based on correct spectral data, in which its 1H-NMR spectrum revealed three singlet signals at δ 1.94, 2.26, 3.34 ppm for three methyl groups, a doublet signal at δ 3.12 ppm for protons of (CH2-pyrazole), a singlet signal at δ 3.95 ppm for the proton of , a multiplet signal in the region from δ 7.32 to 7.52 ppm for the aromatic protons, and two singlet signals at δ 8.25 and 10.01 ppm for the NH protons. Its 13C-NMR spectrum showed significant signals at δ 15.72 ppm for (CH3), 17.94 ppm for (CH3), 42.15 ppm for (CH2-pyrazole), 51.22 ppm for , 106.14, 108.24, 120.12, 121.61, 122.12, 123.01, 134.57, 143.09, 152.98, and 159.14 ppm, which represented the aromatic carbons, 163.24 ppm for (C=O), 164.58 ppm for (C=O), 165.19 ppm for (C=O), and 182.12 ppm for (C=S).Additionally, a new polysubstituted pyrimidine derivative containing antipyrine moiety was constructed via the Biginelli three-component cyclocondensation reaction ,44,45,46ative 12   had the greatest effect on E. coli. With inhibition zones of 16.9 mm and 19.0 mm, it had the strongest effect on C. albicans of all the studied fungal strains. Additionally, compound 9 showed potential antibacterial action against E. coli, P. aeruginosa, S. aureus, B. subtilis, C. albicans, and C. neoformans, with inhibition zones of 19.0, 14.2, 17.0, 15.0, and 16.9 mm, respectively, at a concentration of 100 µg/mL (100 ppm). The largest effect was against E. coli and S. aureus with inhibition zones of 14.0 and 13.1 mm, respectively, for compound 4 and 17.5 and 11.3 mm for compound 5 against E. coli and B. subtilis. However, compounds 4 and 5 possessed antibacterial activity that was less potent than compound 9. Additionally, the MICs of every sample that was evaluated  were established, as shown in The results showed that compound 9, 5, and 4 had the best MICs towards the tested bacteria and unicellular fungus, with MICs in the range of 15.62–500 µg/mL. Additionally, E. coli was shown to be the most susceptible of the studied bacteria, with the MICs of compounds 9, 5, and 4 being 15.62, 31.25, and 125 µg/mL, respectively. On the other hand, the MIC of every substance against E. coli, P. aeruginosa, and S. aureus ranged from 31.25 to 500 µg/mL, which was lower than that of B. subtilis.The results showed that, when compared to other examined microbiological strains, compounds E. coli) and unicellular fungi . On the other hand, the utilized standard antibiotics (AMC/Nyst) were more active than the synthesized compound against some tested microbes due to the fact that the concentration used in our synthesized compound 9 , the proposed compounds showed good antibacterial efficacy against some bacterial isolates , compound .D. data , compounE. coli bacteria. According to E. coli is directly correlated to the concentration of compound 9, which was found to be 177.99 µg/mL following the treatment of compound 9 with 1.0 mg/mL. This finding supports compound 9’s antibacterial properties and explains how the formation of holes in the E. coli cell membrane results in the release of proteins from the cytoplasm.The Bradford technique was used to calculate the amounts of protein released in the suspension of the treated 9 made E. coli cell membranes more permeable; therefore, it was plausible to anticipate that membrane permeability would be mistaken for an essential factor in the reduction in bacterial mass. According to these test results, compound Similar results were found when ferrites were used, as described in related studies, which showed concentration-dependent membrane instability in bacterial cells and indicated intracellular substance leakage .Paul et al.  demonstrE. coli. As shown in 9 revealed bacterial groups that generally prolonged and grew with a regular surface, a normal shape, and a normal count.9 (the most active compound), E. coli displayed striking morphological abnormalities  nano-drug, on the other hand, was subjected to SEM imaging against 2 hydration. In addition, they play a pivotal role in many cellular and physiological processes. In the present study, an in silico docking technique is used to investigate the binding mode of actions of the newly synthesized compounds and a reference drug against the target enzyme E. coli β-carbonic anhydrase. From the data obtained, the newly compounds displayed respectable fitting to the active site residues of the enzyme, which showed binding energies ranging from −9.7 to −7.0 kcal/mol. Compound 9 unveiled the best binding energy  and showed H-bond and arene–sigma interactions with the residues TRP64 and TYR63, respectively. On the other hand, compound 3 showed the lowest binding energy  against the target enzyme, as represented in Carbonic anhydrases CAs are important metalloenzymes widely present in all living organisms and catalyze the essential reaction of CO9, as an example, were calculated using the ADMET lab tool, by plotting radar showing 13 properties 2SO solutions on a BRUKER 500 FT-NMR system spectrometer , and chemical shifts were expressed in ppm units using TMS as an internal reference. Mass spectra were recorded on a GC-MS QP1000 EX Shimadzu . Elemental analyses were carried out at the Microanalytical Center of Cairo University, Egypt.All melting points were uncorrected and measured using an electrothermal device. The IR spectra were recorded (KBr discs) using the Shimadzu FT-IR 8201 PC spectrophotometer . 1  and the methyl hydrazinecarbodithioate 2  in 20 mL isopropyl alcohol was stirred at room temperature for 2 h, and the reaction was monitored by TLC. The solid was collected and washed with (water/ethanol) the recrystallized from the ethanol to give the desired derivative. Yellow crystals (85%); m.p.: 200–202 °C, FT-IR : v 3296 (N-H), 1664 (N-C=O), 1620 (C=N), 1595 (C=C); 1H-NMR (DMSO-d6): δ 2.47 , 2.60 , 3.26 , 7.30–7.51 , 8.05 , 13.03 ;13C-NMR : δ 12.22 (CH3), 18.48 (S-CH3), 34.09 (N-CH3), 123.70 (Ar), 123.88 (Ar), 125.82 (Ar), 127.82 (Ar), 129.26 (Ar), 132.82(Ar), 151.53(Ar), 155.18(CH), 164.41(C=O), 195.81 (C=S); MS m/z (%): 320 . Anal. Calcd. for “C14H16N4OS2” (320): C, 52.48; H, 5.03; N, 17.49 Found: C, 52.42; H, 5.01; N, 17.43%.A mixture of 4-antipyrinecarboxaldhyde 3  and the selected derivatives of the hydrazonoyl halides (5 mmol) and 2–3 drops of diisopropylethylamine (DIPEA) as a catalyst in 10 mL ethanol was stirred at room temperature for 2 h. The stirring continued for approximately 5 h, and the reaction was monitored by TLC. The solid was collected and washed with (water/ethanol) the recrystallized from the proper solvent to give the desired derivatives 4–9, respectively.A mixture of compound 4--ylidene)hydrazono)methyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (4), yellow crystals from acetic acid (78%); m.p. 260–261 °C, FT-IR : 1684 (C=O), 1675 (N-C=O), 1610 (C=N), 1580 (C=C); 1H-NMR (DMSO-d6): δ 2.42 , 2.56 , 3.22 , 7.27–7.7.96 , 8.09 ; 13C-NMR : δ 12.34 (CH3), 24.28 (CH3), 34.21 (N-CH3), 94.12 (Ar), 121.32 (Ar), 121.72 (Ar), 122.50 (Ar), 123.70 (Ar), 123.88 (Ar), 125.82 (Ar), 127.82 (Ar), 129.26 (Ar), 132.82(Ar), 133.12(Ar), 134.22 (Ar), 134.82 (Ar), 151.53 (Ar), 158.18 (C=N), 163.7 (H-C=N), 164.41 (C=O), 195.81 (C=O); MS m/z (%): 432 . Anal. Calcd. for “C22H20N6O2S” (432): C, 61.10; H, 4.66; N, 19.43; Found: C, 61.12; H, 4.61; N, 19.38%.4-(5-acetyl-3-(4-nitrophenyl)-1,3,4-thiadiazol-2(3H)-ylidene)hydrazono)methyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (5), yellowish brown crystals from acetic acid (62%); m.p. 245–247 °C, FT-IR : 1686 (C=O), 1672 (N-C = O), 1600 (C=N), 1580 (C=C); 1H-NMR (DMSO-d6): δ 2.36 , 2.48 , 3.22 , 7.06–7.47 , 7.94 ; 13C-NMR : δ 12.36 (CH3), 24.18(CH3), 34.22(N-CH3), 95.22 (Ar), 120.82 (Ar), 122.72 (Ar), 122.98 (Ar), 123.78 (Ar), 123.18(Ar), 124.62 (Ar), 128.52 (Ar), 129.16 (Ar), 132.52 (Ar), 133.22 (Ar), 134.12 (Ar), 134.82 (Ar), 151.23 (Ar), 158.18 (C=N), 163.18 (H-C=N), 163.41 (C=O), 197.81(C=O); MS m/z (%): 477 . Anal. Calcd. for “C22H19N7O4S” (477): C, 55.34; H, 4.01; N, 20.53; Found: C, 55.29; H, 3.97; N, 20.46%.Ethyl 4-(4-chlorophenyl)-5-methylene)hydrazono)-4,5-dihydro-1,3,4-thiadiazole-2-carboxylate (6), yellow crystals from acetic acid (82%); m.p. 175–177 °C, FT-IR : 1675 (N-C = O), 1715(C=O), 1615 (C=N), 1600 (C=C); 1H-NMR (DMSO-d6): δ 1.31, 2.63 , 3.30 , 4.36, 7.34–7.60 , 8.19 ; 13C-NMR : δ 12.33 (CH3), 12.35 (CH23CH), 13.93 (N-3CH), 62.77 (2CHCH3), 86.40 (Ar), 99.75 (Ar), 123.25 (Ar), 125.78 (Ar), 127.67(Ar), 129.00(Ar), 129.19 (Ar), 133.19 (Ar), 134.48 (Ar), 138.20 (Ar), 149.95 (Ar), 152.86 (Ar), 158.30(Ar), 163.30 (CH), 163.71 (C=O), 168.72 (C=O); MS m/z (%): 498 , 496 . Anal. Calcd. for “C23H21ClN6O3S” (496): C, 55.59; H, 4.26; N, 16.91; Found: C, 55.59; H, 4.26; N, 16.91%.Ethyl-5-methylene)hydrazono)-4-(4-nitrophenyl)-4,5-dihydro-1,3,4-thiadiazole-2-carboxylate (7), yellowish brown crystals from dioxane (76%); m.p. 157–159 °C, FT-IR : 1668 (N-C=O), 1725 (C=O), 1600 (C=N), 1560 (C=C); 1H-NMR (DMSO-d6): δ 1.30 , 2.48 , 3.29 , 4.33 , 7.33–7.57 , 8.35 ; 13C-NMR : δ 12.28 (CH3), 12.37 (CH23CH), 13.95 (N-3CH), 61.97 (2CHCH3), 86.40 (Ar), 123.27 (Ar), 125.18(Ar), 127.77(Ar), 129.12(Ar), 129.16 (Ar), 133.18 (Ar), 134.28 (Ar), 138.22 (Ar), 149.15 (Ar), 151.96 (Ar), 157.33 (Ar), 163.32 (CH), 163.77 (C=O), 165.82 (C=O); MS m/z (%): 507. Anal. Calcd. for “C23H21N7O5S” (507): C, 54.43; H, 4.17; N, 19.32; Found: C, 54.47; H, 4.12; N, 19.28%.5-methylene)hydrazono)-N-phenyl-4-(p-tolyl)-4,5-dihydro-1,3,4-thiadiazole-2-carboxamide (8), yellow crystals from ethanol (68%); m.p. 260–262 °C, FT-IR : 3315(NH), 1662 (N-C = O), 1680 (C=O), 1615 (C=N), 1598 (C=C); 1H-NMR (DMSO-d6): δ 2.31, 2.45 , 3.32 , 7.31–8.06 , 8.15 , 10.63 ; 13C-NMR : δ 12.36 (CH3), 20.51 (CH3), 34.06 (N-CH3), 100.12 (Ar), 120.89 (Ar), 121.72 (Ar), 124.50 (Ar), 125.62(Ar), 127.52(Ar), 128.58 (Ar), 129.12(Ar), 129.20(Ar), 146.61(Ar), 147.00 (Ar), 148.63 (Ar), 156.24 (C=O), 162.24 (CH), 163.45(C=O); MS m/z (%): 507. Anal. Calcd. for “C28H25N7O2S” (523): C, 64.23; H, 4.81; N, 18.73; Found: C, 64.19; H, 4.78; N, 18.68 %.5-methylene)hydrazono)-4-(4-nitrophenyl)-N-phenyl-4,5-dihydro-1,3,4-thiadiazole-2-carboxamide (9), brown crystals from ethanol (63%); m.p. 281–283 °C, FT-IR : 3322(NH), 1668 (N-C=O), 1680(C=O), 1615 (C=N), 1600 (C=C); 1H-NMR (DMSO-d6): δ 2.50 , 3.28 , 7.21–7.78 , 8.08 , 10.79 ; 13C-NMR : δ 12.36 (CH3), 32.12 (N-CH3), 98.14 (Ar), 121.89 (Ar), 122.74 (Ar), 123.51 (Ar), 124.52 (Ar), 126.82 (Ar), 127.61(Ar), 128.15 (Ar), 128.28 (Ar), 145.62 (Ar), 146.50 (Ar), 149.83 (Ar), 155.24(C=O), 163.24 (CH), 163.55 (C=O); MS m/z (%): 554 . Anal. Calcd. for “C27H22N8O4S” (554): C, 58.48; H, 4.00; N, 20.21; Found: C, 58.42; H, 3.95; N, 20.17%.Ethyl 4--6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (10): A mixture of 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carbaldehyde (1) , ethyl acetoacetate , and thiourea  was dissolved in 15 mL DMF with the addition of a few drops of sulfuric acid. The reaction mixture was heated under reflux for 5hrs. After cooling, the solid formed was separated and recrystallized from dioxane as yellow crystals; Yield (83%); m.p. 212–214 °C, FT-IR : 3415, 33821(NH), 668 (N-C=O), 1735(C=O), 1620 (C=N), 1600 (C=C); 1H-NMR (DMSO-d6): δ 1.02, 2.17, 3.23 , 3.50, 3.96, 7.29–7.45 , 12.23 , 12.29 ; 13C-NMR : δ 13.57 (CH23CH), 15.58 (CH3), 18.54 (CH3), 52.02 , 61.66 (2CHCH3), 103.84 (Ar), 106.44 (Ar), 120.20(Ar), 124.41(Ar), 126.92(Ar), 134.47(Ar), 153.09 (Ar), 160.98 (Ar), 166.18(C=O), 167.89(C=O), 176.14 (C=S); MS m/z (%): 386 . Anal. Calcd. for “C19H22N4O3S” (386): C, 59.05; H, 5.74; N, 14.50; Found: C, 58.98; H, 5.72; N, 14.44%.4--6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbohydrazide (11): Ethyl 4--6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (10)  and hydrazine hydrate (5mmol) were mixed in 20 mL absolute ethanol. The reaction mixture was heated under reflux for 5hrs. After cooling, the solid formed was separated and recrystallized from ethanol as white crystals; Yield (85%); m.p. 225–227 °C, FT-IR : 3415 (NH), 3386 ,1664 (N-C=O), 1682 (C=O), 1620 (C=N), 1590 (C=C); 1H-NMR (DMSO-d6): δ 2.12 , 3.34 , 3.65 , 5.36 , 6.15–6.55 , 8.06 , 8.79 ; 13C-NMR : δ 15.72 (CH3), 17.94(CH3), 53.22 , 104.84 (Ar), 108.44 (Ar), 121.22 (Ar), 123.61(Ar), 124.92(Ar), 133.57(Ar), 143.09(Ar), 152.98(Ar), 164.58(C=O), 165.19 (C=O), 182.12 (C=S); MS m/z (%): 372. Anal. Calcd. for “C17H20N6O2S” (372): C, 54.82; H, 5.41; N, 22.56; Found: C, 54.86; H, 5.37; N, 22.51%.1,5-dimethyl-4--2-thioxo-1,2,3,4-tetrahydropyrimidin-4-yl)-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (12): 4--6-methyl-2-thioxo-1,2,3,4-tetra hydropyrimidine-5-carbohydrazide (11)  and ethyl acetoacetate  were refluxed in 20 mL ethanol containing 1–3 drops of acetic acid for 5h; the solid formed while heating was separated and recrystallized from acetic acid as beige crystals. Yield: 71%, m.p. 271–273 °C, FT-IR : 3412, 3374 (NH), 1680 , 1665 (N-C = O), 1600 (C=N), 1560 (C=C); 1H-NMR (DMSO-d6): δ 1.94 , 2.26 , 3.12 , 3.34 , 3.95, 7.32–7.52 , 8.25 , 10.01 ; 13C-NMR : δ 15.72 (CH3), 17.94 (CH3), 42.15 (CH2-pyrazole), 51.22 , 106.14 (Ar), 108.24 (Ar), 120.12 (Ar), 121.61 (Ar), 122.12 (Ar), 123.01 (Ar), 134.57 (Ar), 143.09 (Ar), 152.98 (Ar), 159.14 (Ar), 163.24 (C=O), 164.58 (C=O), 165.19 (C=O), 182.12 (C=S); MS m/z (%): 438 . Anal. Calcd. for “C21H22N6O3S” (438): C, 57.52; H, 5.06; N, 19.17; Found: C, 57.56; H, 5.02; N, 19.12%.Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853), Gram-positive bacteria (Staphylococcus aureus ATCC 25923 and Bacillus subtilis ATCC 6051), and unicellular fungi . The agar well diffusion method was used to test the antimicrobial activity of the synthesized samples against six microorganisms, including Gram-negative bacteria .The pathogenic microorganisms that were screened were known to cause UTIs. While the fungal strains were seeded on malt extract agar (MEA) plates and cultured for 3–5 days at 28 ± 2 °C before being maintained at 4 °C for subsequent usage, the examined bacteria were inoculated on nutrient agar for one day at 37 °C . The minThe specific and fixed wavelength used for detecting the optical density for the bacterial growth (at 600 nm) was completely different from the optical density for the synthesized sample. A negative control  and positive control (the tested microbes and the nutrient broth) were conducted for these purposes; additionally, another control like the synthesized sample alone was used to compare the conducted results as an auto-zero purpose. The MICs were determined as the lowest sample dilution capable of inhibiting visible bacterial growth.To evaluate the antimicrobial capability of the synthesized materials, the ZOI test must be combined with the use of nystatin (NS) as an antifungal positive control and amoxicillin/clavulanic acid , a common antibacterial drug.E. coli, the most sensitive bacteria. In 5.0 mL nutrient broth tubes, the bacterial suspension was adjusted to 0.5 McFarland (1 × 108 CFU/mL). Each tube under inspection had a single addition of compound 9. At 2 h intervals up to 24 h after treatment, the absorbance of the bacterial growth was measured (wavelength: 600 nm). To obtain the typical growth curve, the average of the triplicate data was compared to the hourly intervals [According to Huang et al., the growth curve test was used to investigate how chemical 9 affected the growth of ntervals ,52.8 CFU/mL) was chosen for the pure 18 h bacterial culture, and 100 µL of it was put into 10 mL of the nutritional broth containing compound 9. As a control, a broth devoid of component 9 was infused with culture. All of the treated samples were centrifuged for 15 min at 5000× g rpm after being incubated at 37 °C for 5 h. A total of 100 µL of supernatants and 1 mL of Bradford reagent were blended for each of the various samples. At 595 nm, optical density was measured following 10 min of incubation in the dark. Furthermore, 0.5 McFarland (1 × 108 CFU/mL) in nutrient broth tubes, and about 5.0 mL of the adjusted bacterial suspension was mixed with 1.0 mL of the prepared compound 9 at a concentration of 15.62 µg/mL  and treated microorganisms.The bacterial suspensions were adjusted to 0.5 McFarland (1 × 10p < 0.05) and Duncan’s methods. SPSS software version 15 was used to examine the accepted results. It must be noted that all the biological tests were repeated three times.The statistical analysis of the obtained results was investigated after applying a one-way ANOVA (at https://www.rcsb.org/) [E. coli β-carbonic anhydrase [The 2D structures of compounds were sketched using ChemDraw 16 and then converted to 3D structures and minimized using OpenBabel GUI . The tarsb.org/)  under PDnhydrase . The filnhydrase  in Disconhydrase . The dugE. coli, P. aeruginosa, S. aureus, B. subtilis, C. albicans, and C. neoformans, whereas the MICs for compounds 9, 5, and 4 were 15.62, 31.25, and 125 µg/mL, respectively. It was discovered that the amount of cellular protein released from E. coli is directly correlated to the quantity of compound 9, which was found to be 177.99 µg/mL following treatment with 1.0 mg/mL of compound 9. This finding supports compound 9’s antibacterial properties and explains how the formation of pits in the E. coli cell membrane results in the release of proteins from the cytoplasm. A substance must stick to its target site on microbial cells and establish a specific number of crucial regions associated with its level within pathogenic microorganisms in order for it to possess antimicrobial potentials that may eliminate those pathogenic microbes. The docking studies proved that compound 9 declared a greater activity than other synthesized compounds.The present study overlays the synthesis of a new series of thiadiazole and pyrimidine moieties attached to antipyrine analogue 2–12, and their structures were confirmed via spectral and elemental analyses. The antimicrobial potential was estimated through in vitro ZOI and MIC. On the other hand, the antibacterial reaction mechanism was tested through a membrane leakage assay and SEM imaging technique. In comparison to AMC/Nyst, the industry standard antimicrobial agent, all developed compounds showed promising antibacterial activity against all of the evaluated bacterial and fungal species. In comparison to AMC/Nyst, compounds 4, 5, and 9 were noticeably more active. With inhibition zones of 19.0, 14.2, 17.0, 15.0, 16.9, and 9.5 mm, respectively, compound 9 at a dosage of 0.1 mg/mL showed potential antibacterial action against


Augmented reality (AR) has emerged as a promising technology in educational settings owing to its engaging nature. However, apart from applications aimed at the autism spectrum disorder population, the potential of AR in social-emotional learning has received less attention.This scoping review aims to map the range of AR applications that improve social skills and map the characteristics of such applications.In total, 2 independent researchers screened 2748 records derived from 3 databases in December 2021—PubMed, IEEE Xplore, and ACM Guide to Computing Literature. In addition, the reference lists of all the included records and existing reviews were screened. Records that had developed a prototype with the main outcome of improving social skills were included in the scoping review. Included records were narratively described for their content regarding AR and social skills, their target populations, and their outcomes. Evaluation studies were assessed for methodological quality.A total of 17 records met the inclusion criteria for this study. Overall, 10 records describe applications for children with autism, primarily teaching about reading emotions in facial expressions; 7 records describe applications for a general population, targeting both children and adults, with a diverse range of outcome goals. The methodological quality of evaluation studies was found to be weak.Most applications are designed to be used alone, although AR is well suited to facilitating real-world interactions during a digital experience, including interactions with other people. Therefore, future AR applications could endorse social skills in a general population in more complex group settings. Digital technology has begun to move beyond the constraints of static, screen-based media toward more dynamic, immersive environments such as virtual reality (VR). One specific technology that is embedded in the concept of VR and is being increasingly used in various sectors is augmented reality (AR). AR creates visual situations where virtual components overlap with the real world, inviting the user’s complicity in the illusion that these virtual components exist in the real world. As such, AR does not create a virtual environment per se but acts as a digital supplement to the real environment , clearlyThese advances have made AR a successful technology for commercial gaming (the most popular being the 2016 Pokémon Go by Niantic) and for informal learning sites, such as exhibits or museums to increase interaction with showcased topics . In addiSocial skills are crucial throughout life for social functioning  and for social competence, soft skills, emotional learning, or social behavior  or cooperative gameplay [The Woods]). Finally, 1 application (UP2U) uses a group setting by analyzing and teaching people to be more attentive to each other.Considering the topic of social skills, we also examined the social settings of the applications. Of the 17 included applications, 10 were used as a single-player experience. In addition, 6 applications are performed in dyads, including both interactions with a human facilitator, therapist, or teacher who knows the system and experiences for pairs of naive users  described the feasibility of the technical side of the application.Both usability and intended outcomes were generally positive in all the studies that tested the applications. A total of 12 records reported usability outcomes. We describe usability as a term that includes usability, feasibility, and acceptability. Moreover, 2 records report that there were no adverse effects and no conflicts; 4 records report that the users were able to understand and complete the intervention , and 8 of the records report that participants found the application interesting and engaging or that users rated the application highly (“excellent” or “brilliant”). Only 1 record  symptoms , or verbal affirmation by participants that the application promotes and helps with the intended outcome.Although one of our eligibility criteria was that the application had to have an intended and transferable effect on social skills, during our review process, we found a variety of records that show how AR can be used as support in situations that require social skills or skills related to social skills. As our aim with this scoping review was to give an overview of existing literature, in this section, we want to give some examples of applications supporting users in social situations.BloxAR [For instance, AR has been found to improve narrative skills during storytelling compared with non-AR story creation, possibly because of the engaging nature of AR . In addiBloxAR , a sociaIn this systematic scoping review, we mapped existing literature on AR applications that improve social skills. We found 17 records that fit our inclusion criteria, that is, reporting AR applications intended to improve social skills as the main goal. As expected due to existing reviews, most AR applications that teach social skills were developed for an autistic population . These applications aim to improve emotional expression recognition, social greeting behavior, or gaze direction in children. Applications for the general populations are more diverse and include emotional expression recognition, perspective taking, and empathy, as well as more specific topics such as destigmatization or antiphubbing behavior for both children and adults.Most of the records we reviewed focused on developing applications for children with autism, which is reasonable, given that social skills deficits are 1 of the 2 defining characteristics of autism . Our finAR is considered a promising tool for teaching because of its potential for interaction between the virtual and real worlds and its ability to facilitate visualization . The resStrengths lie in the inclusion of the target group in the design and development process, the iterative process that many records describe, and the creative detail and hard work that often goes into the development of a serious game or intervention. Limitations are mostly found in the methodology of evaluation of the applications, especially in the small sample size of studies targeting an autistic population, where fewer than 5 children were tested. Evaluations rarely follow rigorous methodology . Although iterative development for technical applications is necessary and reporting of preliminary results and evaluations is desirable, our results suggest that systematic and methodologically rigorous evaluations of AR applications for promoting social skills are still lacking.This review was conducted in a structured and transparent manner, and the authors tried to eliminate mistakes by repeating screening at the abstract level. The main limitation of this scoping review is that due to the broad field of social skills, our search criteria might have missed some AR applications related to social skills. For example, emotion regulation and empathy are vital skills for adaptive interpersonal relations and should thus be included in the field of social skills. However, owing to the large number of additional records, we did not include these strings as separate search strings. Although being a limitation, some facts show that our search strategy yielded results that appropriately reflect the social skills training field. First, our final data set contains studies related to empathy, which shows that our search had the potential to also find records with this specific skill. In addition, all but one of the records identified through our additional search of existing reviews, reference lists, and follow-up studies were duplicates or had to be excluded, indicating that our search terms were adequate. Further reviews could broaden the search and include specific terms such as “emotional learning” or “empathy.” Second, the interdisciplinarity of the topic and consequent limitations in the databases and search terms used might have resulted in the overlooking of certain records. Finally, the heterogeneity of the included records posed challenges in the synthesizing of the findings. However, different aspects revealed the focus of the current literature, for example, the emphasis on children with autism, which can be valuable for guiding future research.Our findings suggest that AR applications have the potential to enhance social skills, as indicated by the evaluations of player experience and usability. Although the intended outcomes were only preliminarily tested in most of the included studies, AR applications can be highly engaging tools for social-emotional learning in psychological, digital, and educational settings.MOSOCO, uses AR to teach social interaction skills to children with autism during real-time conversations with other children. Their results show that the app helps both children with autism and neurotypical children during their social interactions with each other. Although the sample size in their study was small, this shows the great potential of such applications to reduce stigma and lead to better social connections in real-world and real-time complex social settings in autistic, general, and mixed populations.The search strings “cooperation” and “collaboration” were included because of their common appearance as keywords in AR contexts. The results showed that these 2 strings were not very relevant for our final included records. Social skills are mostly taught in a single-user setting or with a human facilitator. Considering the advantage of AR in easily enabling cooperative or collaborative situations, future research could explore ways to improve social skills in pairs or even groups. The times have passed when the digital world was not social. Nowadays, most digital tools, such as apps and online gaming, include or are exclusively for connecting with other people. However, many of these web-based interactions happen while both or all people are at different locations. AR not only has the advantage of interacting with digital components in the real world but also has the potential for the user to interact with other people while using a digital tool in real life. AR offers the exciting possibility of playing a digital game or interacting with a digital tool while being in the same room with other people who the player interacts with, as such, aiming to improve skills in complex and real-time social situations. As an example, one of our included records, This scoping review describes the range and characteristics of applications using AR to improve social skills. Applications have been developed for autistic and general populations. Most often, they target emotion recognition, although this varies. The evaluations show promising results in terms of both the usability and intended outcomes of these applications. In future work, more focus should be placed on high-quality evaluations to further substantiate these results, and more complex social interactions in real-world settings should be explored.


Editorial on the Research TopicLeadership in teamwork: enhancing rehabilitation medicine best practiceThe primary aim of this research topic was to bring together a collection of papers that focused on leadership and teamwork in Rehabilitation Medicine to shed light on approaches and key factors affecting outcomes of person-centered care and the impact on rehabilitative care in general. Our main goals were (1) Identification of effective leadership models in the teamwork of person-centered care that could bring forth innovative practices in rehabilitation, (2) To advocate for real world interest in providing studies and documents to develop a critical mass of data to enhance person-centered care, and, (3) To promote evidence-based information and education on effective leadership in person-centered teamwork rehabilitation practice.•Historical perspectives of leadership in rehabilitation practice.•Models of leadership in rehabilitation teamwork and their attributes.•Leadership experience in person-centered care rehabilitation practice.•Person-centered care as a basis for modelling leadership roles in healthcare and or rehabilitation practice.•Theoretical basis and thesis generated by the application of the various healthcare, medical, social, anthropological and other models specific to rehabilitation practice.•Theoretical models of leadership in Rehabilitation Medicine.•Theoretical models of teamwork in rehabilitation practice.We welcomed the submission of manuscripts that included, but not limited to, the following topics:Thorsten Meyer et al., titled “Cooperative leadership as a condition for patient reported rehabilitation success”, presents qualitative evidence for the importance of interdisciplinary teamwork and collaborative leadership. From France, the pilot study from R. Lenoir dit Caron et al. shows that team-based exercise programs proved superior to personalized ones. Finally, from Canada, Gillian King et al. shared their experience innovating a transition strategy at a pediatric rehabilitation hospital. The key elements identified in team members serve as useful lessons on team dynamics.We attracted submissions on a diverse range of relevant subjects from three continents; two from Asia, two from Europe and one from North America. Taslim Uddin from Bangladesh submitted a short communication that highlights the challenges for team leadership in developing countries. These include curriculum course content, monitoring systems, infrastructure development, funding, attitude, education level of people with disabilities, ethics and disasters. From China, Ping Zhou brought out an emerging rehabilitation team member that we cannot do without currently, i.e., a rehabilitation engineer. From Germany, the submission from These submissions are so diverse in their content, ranging from conventional and emerging team memberships, cohesiveness, and shared responsibilities to a person-centered exercise program. The relative scarcity of literature and submissions on the core principles of rehabilitation practice that this research topic called for implies rehabilitation has only just begun to nurture the current and future rehabilitation professionals in the field. Person-centered care, teamwork and leadership in rehabilitation are dynamically intertwined. Each of these unique components require consistent education of rehabilitation health care providers, data driven action and evidence-based practice. Rehabilitation, as conventionally practiced, is at a critical juncture requiring new skills, knowledge, data, and evidence to meet the exciting challenge of progression in the specialty.Bickenbach et al.). Soft systems thinking approach can take care of multistakeholder real-world needs that are so often disregarded. Complex societal situations demand critical systems thinking approach to solve the most trivial daily issues encountered in rehabilitation practice.Person-centered care can only be realized by consciously recognizing the person as the expert in their lives and incorporating that critical component in every step of the way throughout all aspects of rehabilitation. Persevering in person-centered care calls for a hard, soft, and critical systems thinking approach  that is Inter, multi and transdisciplinary teamwork is key to a cohesive effort in processing person-centered rehabilitative care. The expanse of knowledge and skills in the spectrum of evidence-based practice for health, wellness and functionality of individuals requires a team effort; woe to the practitioner who practices with a solo mindedness.The art of practicing leadership in daily rehabilitation practice requires excellent communication skills, strategic planning, awareness of social determinants of health of persons receiving rehabilitation services plus cultural mores, and the inevitable environmental changes. A leader who is selfless opens doors and grants opportunities for rehabilitation team members to grow individually as well as a robust team. Effective and efficient person-centered care and teamwork that are perpetually practiced can propagate excellent leadership.Turning data into action may seem a while away, but person-centered care and teamwork in rehabilitation are here to stay. Our creative innovative ways will be testimony to our adherence to these core principles in our specialty. Along with good leadership, they will remain important determinants of Rehabilitation Medicine best practice that will benefit the one in three people in the world who needs rehabilitation in the course of their disease or injury .


Treatment of esophageal cancer is based on tumor-node-metastasis (TNM) classification, and surgical treatment is chosen based on the patient’s ability to tolerate surgery. Surgical endurance partly depends on activity status, with performance status (PS) generally used as an indicator. This report describes a 72-year-old man with lower esophageal cancer and an 8-year history of severe left hemiplegia. He had sequelae of cerebral infarction and a TNM classification of T3, N1, and M0, and was judged ineligible for surgery because his PS was grade three; he underwent preoperative rehabilitation with hospitalization for 3 weeks. He had been able to walk with a cane in the past, but once he was diagnosed with esophageal cancer, he began using a wheelchair and was dependent on assistance from his family in his daily life. Rehabilitation consisted of strength training, aerobic exercise, gait training, and activities of daily living (ADL) training for 5 h a day, according to the patient’s condition. After 3 weeks of rehabilitation, his ADL ability and PS improved sufficiently for surgical indication. No complications occurred postoperatively, and he was discharged when his ADL ability was higher than that before preoperative rehabilitation. This case provides valuable information for the rehabilitation of patients with inactive esophageal cancer. Treatment plans for patients with esophageal cancer are determined in accordance with the Japanese guidelines based on tumor-node-metastasis (TNM) classification . In caseThe reported incidence of postoperative pulmonary complications associated with esophagectomy ranges from 30–60% , and hasPatients with cerebrovascular disorders suffer from a wide range of sequelae, including higher brain dysfunction, motor paralysis, and sensory impairment, depending on the site of brain damage . This reThis case report describes a patient with esophageal cancer with sequelae of cerebral infarction and a TNM classification of T3, N1, and M0, who was determined to not be eligible for surgery because his PS was 3. Instead, he underwent preoperative rehabilitation with hospitalization for 3 weeks. This is a detailed description of the patient’s rehabilitation until his PS improved and surgery became possible, as well as the course of his rehabilitation until discharge after surgery.The patient was a 72-year-old man with esophageal cancer. He visited his primary care physician complaining of esophageal transit disturbance, and was diagnosed with lower esophageal cancer by upper gastrointestinal endoscopy and computed tomography . The patient had a cerebral infarction 8 years prior, with left hemiplegia as an aftereffect. However, he was able to walk independently with the use of a cane and could perform ADLs independently. After being discharged from the hospital, the patient did not undergo outpatient rehabilitation or exercise on his own in order to prevent the deterioration of physical function. Thereafter, his activity gradually declined with age, and at the time of his diagnosis of esophageal cancer, he used a gait aid and a lower limb brace to walk around at home and a wheelchair for outdoor mobility. The patient was not in the habit of performing exercise and spent > 50% of the day in bed. The patient’s PS was 3 at the time of diagnosis, and after a comprehensive review of his operative tolerance, surgery was not indicated. However, the gastroenterological surgeon consulted with the Department of Rehabilitation about whether PS could be improved through rehabilitation, and the Department of Rehabilitation began to consider it.2 max was measured. The 6 MWT measured a 6-min walking distance with maximal effort, as indicated by the American Thoracic Society [2 max in CPET was 821 mL/min and 14.1 mL/kg/min; 6 MWT was 105 m; and 10 MWT was 33.2 s. Lower limb muscle strength in the HHD assessment was 80 N in the right leg and 42 N in the left leg.At the time of the examination in the Department of Rehabilitation, the Glasgow Coma scale was E4V5M6 ,14 and t Society . For the Society . For the Society . The pat2 max was 14.1 mL/kg/min, which is low enough for a concerning high risk of postoperative complications, we aimed to improve VO2 max as much as possible before surgery.The patient’s PS was thought to have declined due to the loss of muscle strength in the healthy side of the lower limb and the impaired mobility caused by severe left hemiplegia. However, since the patient had previously been able to walk with a cane, the paralyzed leg was probably strongly affected by muscle weakness due to disuse, which was also apparent in the healthy leg muscles; therefore, it was judged that there was sufficient room for improvement through rehabilitation, and rehabilitation was started on the same day. The main objective of rehabilitation was to improve PS by increasing muscle strength in both lower limbs and improving ADL. In addition, since the patient’s VOThis hospital provides high-intensity, long-duration rehabilitation therapy tailored to the patient’s general condition ,23. Afte2 max of 959 mL/min and 16.6 mL/kg/min. Walking ability tests were performed without assistance from a physical therapist, as the patient was walking independently with a cane and wearing a brace. Consequently, his 6 MWT distance extended to 125 m, and his 10 MWT time decreased to 30.9 s. The HHD results also increased to 120 N and 82 N on the right and left sides, respectively. Due to this improvement in physical function, the indication for surgery was reconsidered at a preoperative conference of the Gastrointestinal Surgery Department. Therefore, the patient was judged to be operable, and surgery was subsequently performed.The results of the 22-day preoperative rehabilitation are shown in The surgical techniques performed were: thoracoscopic subtotal esophagectomy, thoracoscopic gastric tube creation, two-region lymphatic dissection, and reconstruction of the posterior sternal pathway gastric tube. The operation time was 8 h and 21 min, and the operative blood loss was 45 mL. The postoperative diagnosis was esophageal squamous cell carcinoma . Postoperatively, the patient was admitted to the intensive care unit for management.2 max of 980 mL/min and 17.8 mL/kg/min; 6 MWT was 128 m; 10 MWT was 26 s, showing improvement in comparison to his results on the day before surgery. There was no dysarthria or dysphagia after the CVA onset. Postoperatively, there was no hoarseness or obvious dysphagia; a jelly diet was started on POD 11. On POD 15, the diet was changed to a soft, bite-sized diet. In addition, there were no adverse events during rehabilitation from the preoperative period to discharge, and no postoperative complications occurred. After being discharged from the hospital, the patient was followed up by a gastroenterological surgeon once a month; there has been no recurrence, and the patient is living independently.On the first postoperative day (POD), at 8:00 a.m. the patient was extubated from the ventilator and at 11:00 a.m. transferred to the general ward. Mobilization was performed at 11:30 a.m., and gait training began with assistance in cooperation with a nurse. Supplemental oxygen therapy was administered using a mask at a flow rate of 10 L/min. The patient had a right chest drain, a cervical drain, and a J-tube. A. The paIn accordance with the local legislations and institutional requirements, ethical review and approval were not required for this case report. In order to publish any potentially identifiable images or data included in this article, a written informed consent was obtained from the patient and his family. This study conforms to all case report guidelines and reports the required information accordingly.Most of previous reports on preoperative rehabilitation for patients undergoing esophageal cancer surgery have focused on preventing postoperative respiratory complications, atelectasis, and shortening hospital stay duration ,7,8,9,102, peak workload, walking speed, and walking endurance increased with only 20–40 min of endurance exercise 3–5 times per week for 10 weeks [A previous study reported a preoperative rehabilitation program for the prevention of pulmonary complications consisting of respiratory rehabilitation, including respiratory muscle and thoracic stretching to increase pulmonary compliance, deep breathing and abdominal breathing training, sputum training, muscle strength training using weights, and 20 min of bicycle ergometer exercise, for approximately 60 min per day, respectively . Akiyama10 weeks . Zaiki e10 weeks . Althoug2 max correlated strongly with survival in patients with esophageal and gastric cancer [2 was found to be higher in patients without postoperative complications than in those with postoperative complications [2 max was improved by preoperative rehabilitation, which may have helped prevent complications. In addition to the preoperative improvement in ADL ability, the patient’s general condition did not deteriorate, and he did not experience any complications; this was due to the implementation of muscle strength training and aerobic exercises, as well as the gradual increase in exercise load, which enabled discharge home with better ADL ability than before preoperative rehabilitation had begun.A review by Guinan et al.  indicatec cancer , and preications . In thisThis study reported one case only. The cerebrovascular disease patients have a wide range of sequelae and a varying disease severity; thus, it is difficult to generalize the content and course of rehabilitation before and after surgery. In some cases, two-stage surgery may be indicated. However, this report describes a patient with esophageal cancer who was judged to be ineligible for surgery due to low activity and tolerance for surgery but became operable after 3 weeks of intensive preoperative rehabilitation. The content and course of rehabilitation in this case may provide valuable information for patients with esophageal cancer and low activity.In some cases of esophageal cancer, providing 3 weeks of high-intensity prolonged preoperative rehabilitation to patients that are ineligible for surgery can improve ADL and PS to the point of surgical indication. Therefore, cancer patients who are judged to be inoperable owing to low activity may benefit from intensive rehabilitation in a hospital before deciding on a treatment plan.


Optimizing the functional status of patients of any age is a major global public health goal. Rehabilitation is a process in which a person with disabilities is accompanied to achieve the best possible physical, functional, social, intellectual, and relational outcomes. The Intermediate Care Unit within the O.U. of Geriatrics and Gerontology of the San Martino Hospital in Genoa is focused on the treatment and motor reactivation of patients with geriatric pathologies. The objective of this study was to identify which factor, among the characteristics related to the patient and those identified by the geriatric evaluation, had the greatest impact on rehabilitation outcomes. Our findings revealed significant correlations between the Barthel Index delta, the 4AT Screening Test, and the number of drugs taken. This association highlights the potential benefits of medication management in enhancing the overall well-being and functional abilities of frail older adults, despite the literature suggesting that polypharmacotherapy is associated with a reduction in functional status and an increase in mortality. These findings underscore the significance of a multidimensional geriatric assessment. Refining and optimising these multidisciplinary approaches is the objective of a more effective geriatric rehabilitation strategy. Functional status refers to an individual’s capability to perform routine daily activities essential for fulfilling basic needs, habitual roles and maintaining health and well-being. Biological factors, cognitive impairment, mood disorders, and other variables can influence an individual’s functional status . OptimizPhysical exercise has emerged as a fundamental strategy for preserving physiological reserves, yielding favourable effects on diverse aspects including musculoskeletal strength, neural health, respiratory and cardiovascular systems, body composition, and metabolism .Rehabilitation, as defined by the Italian Ministry of Health in 2019, is a process in which individuals with disabilities are supported in attaining optimal autonomy across physical, functional, social, intellectual, and relational dimensions while acknowledging their limitations.Similarly, geriatric rehabilitation, as defined by the Dutch National Aged Care Program in 2017, constitutes a multidisciplinary integrated care approach aimed at restoring the functional status of frail elderly individuals after acute events or in cases of functional challenges.In the geriatric setting, rehabilitation often focuses on fall prevention, postoperative rehabilitation, and management of chronic conditions such as arthritis, dementia, and stroke. Geriatric rehabilitation also improves the quality of life of elderly patients through patient and family education, emotional support, and promotion of a healthy lifestyle.Geriatric rehabilitation can be defined as a non-specific therapeutic approach aimed at the sick elderly person at risk of disability or specific when it is implemented on an already disabled patient. The former approach seeks to intervene on the functional loss that follows the interaction between ageing and disease, and the latter aims to recover and maintain the maximum possible level of functional autonomy in the disabled elderly patient population.Multidisciplinarity is indispensable in geriatric rehabilitation to address the intricate needs of frail patients . Key plaThis study was conducted at the Intermediate Care Unit within the Geriatrics and Gerontology Department of San Martino Hospital in Genoa, which specialises in functional recovery, clinical stabilisation and therapeutic optimisation for post-acute phase patients or those with chronic conditions yet to attain hospital discharge criteria. The unit concentrates on treating and reactivating motor functions in individuals grappling with geriatric pathologies, notably encompassing post-stroke patients, those with Parkinsonism, chronic obstructive pulmonary disease, heart disease, hip fractures, and cognitive impairments.A total of 50 patients admitted to the Intermediate Care Unit of the O.U. of Geriatrics and Gerontology of the San Martino Hospital in Genoa were recruited during hospitalisation between November 2022 and March 2023. Of these, 22 were male and 28 were female, aged between 70 and 95 years.The collected data included demographic information, several clinical scales at admission as input, and the clinical assessment of the Barthel index at two time points: admission (T0) and discharge (T1) as outcome. The demographic and clinical characteristics of all participants are summarised in The main objective of this study was to identify which factor, among the characteristics related to the patient and among the characteristics identified by the geriatric evaluation, had the greatest impact on rehabilitation outcomes.The success or failure of geriatric rehabilitation was measured by determining the Barthel Index at entry and discharge within the multidimensional assessment, as explained later.−Gender: according to the current literature, gender could play a role in rehabilitation outcomes . Indeed,−Age: the patient’s chronological age at the time of hospitalisation is considered in our study with the aim of determining whether it could have an impact on the rehabilitation outcome. At the moment, according to our knowledge, there are few studies that have examined this association. The focus of the current literature seems to be the association between cognitive impairment typical of old age and its impact on learning motor skills and, consequently, its influence on geriatric rehabilitation .−Days of hospitalisation: the days of hospitalisation were considered for the evaluation of geriatric rehabilitation because an increase in the length of hospitalisation is typically associated with a higher prevalence of complications, especially in elderly patients . However−Pre-hospitalization Activities of Daily Living (ADL): ADL is a score that examines activities of daily living that are essential for living in a social world as they enable survival and basic well-being, such as bathing, going to the toilet, dressing, and eating . Prehosp−Barthel Index at the time of admission and discharge: this is a score that establishes the patient’s degree of independence. It consists of 10 items that examine common daily activities. Each item is assigned a score whose sum indicates the patient’s degree of autonomy in carrying out daily life activities . In our −Clinical Frailty Scale (CFS) at the time of admission: CFS is a frailty tool that assesses specific domains, including comorbidity, functional status, and cognition, to generate a frailty assessment score ranging from 1 (very fit) to 9 . A score of >4 points indicates frailty . Frailty−Hand Grip Strength Test upon admission: This test measures the maximum isometric force exerted by the muscles of the upper limb. It is performed using a dynamometer that records each person’s strength. It is a simple and reliable measure of maximum voluntary muscle strength. It is an important tool for diagnosing sarcopenia and is widely used as a single indicator to represent overall muscle strength; it can predict not only muscle mass and physical activity but also the incidence of chronic disease, nutritional status, quality of life, independence of daily living, length of hospital stay, and even mortality .−Anticholinergic cognitive burden score (ACB score) at the time of admission: anticholinergic drugs work by blocking the neurotransmitter acetylcholine in the central or peripheral nervous system and have different actions depending on the site . The neu−Number of medications at admission: polypharmacotherapy, defined as the regular use of at least five medications, is common in the elderly and increases the risk of adverse medical outcomes . The ide−Mini Nutritional Assessment Short-Form (MNA-SF) at admission: malnutrition in the elderly results from numerous changes in physiological function with age, for example, decreased food intake, less physical exercise, reduction of intestinal absorption, mental problems, etc., . Since t−4AT Screening Test (4AT) upon admission: This is a tool for assessing the presence of delirium or brief cognitive impairment that is widely used internationally in clinical practise and research . Deliriu−Cumulative Illness Rating Scale (CIRS) at the time of admission: this scale was developed for the assessment of physical pathology and examined 14 independent body domains . Our stuThe factors considered in our study included:Our first inclination was to apply machine learning analysis to the collected data . After tThe difference between the Barthel Index at discharge and at admission (T1 and T0) was used as an output variable to investigate which admission variables predicted the change in patients’ level of autonomy. In particular, Pearson’s correlation coefficient was initially used to measure the relationship between the Barthel Index Delta and other clinical variables at T0, and then highly correlated variables were employed in a multiple linear regression model to predict the outcome.In addition, the nonparametric Mann–Whitney–Wilcoxon (MWW) test was used to verify that there was no significant difference in Barthel Index Delta between genders.t-test for normally distributed continuous variables, the Mann–Whitney–Wilcoxon (MWW) test for not normally distributed continuous variables, and the chi-square test for categorical variables.Subsequently, the patients were categorised into two groups based on their Barthel Index Delta: Low  and High (above 10). Univariate analysis was performed to examine potential significant differences between the two groups. Specifically, we used the parametric p value was considered significant at <0.05. Leave-one-out cross-validation was used to evaluate logistic regression model performance. Principal component analysis was used to visualise how the two groups were discriminated by the selected variables.Statistically significant variables in the univariate analysis were then introduced in a multivariate logistic regression model. All statistical analyses were performed using R version 4.3. The p = 0.004) and a significant negative correlation with 4AT Screening Test  with the outcome. All test results are reported in p = 0.913).The results of the Shapiro–Wilk test are reported in The fitted multilinear regression model was:2 = 0.23, F = 6.91, p = 0.002).The overall regression was statistically significant (Rp = 0.01).Drugs Number significantly predicted Barthel Index Delta .No high significance was found for 4AT Screening Test , necessitating further investigation in a larger geriatric population.Conversely, the presence of delirium, as assessed by the 4AT Screening Test, is associated with declining functional independence, likely due to reduced active participation in physiotherapy, heightened fall risk, and cognitive impairment. Our study’s objective is to heighten the awareness of clinicians treating elderly patients during rehabilitation to early delirium identification, as it influences the success of physiotherapy treatment. Preventive measures, including prescribing techniques and environmental and pharmacological interventions, can mitigate delirium effects.Our unit places particular emphasis on the treatment and motor reactivation of individuals with geriatric pathologies, including post-stroke patients, those with Parkinsonism, chronic obstructive pulmonary disease, heart disease, hip fracture, and cognitive impairment; however, the negative correlation with the presence of delirium indicates the need to broaden geriatric rehabilitation. This should be undertaken with the purpose of motor reactivation in conjunction with a multidisciplinary rehabilitation approach aimed at delaying both functional and cognitive decline and reducing psychological and behavioural disorders by acting on neuroplasticity and functional reserve . IntegraIn summary, the observed correlations emphasise the significance of comprehensive geriatric assessment and collaborative approaches. Refinement and optimisation of these multidisciplinary strategies constitute the aim of an effective geriatric rehabilitation strategy.