Frontiers in Chemistry in March 2019 entitled “In silico Methods for Drug Design and Discovery,” which involved two sections of the journal: Medicinal and Pharmaceutical Chemistry and Theoretical and Computational Chemistry. For the reasons mentioned, this Research Topic attracted the attention of scientists and received a large number of submitted manuscripts. Among them 27 Original Research articles, five Review articles, and two Perspective articles have been published within the Research Topic. The Original Research articles cover most of the topics in CADD, reporting advanced in silico methods in drug discovery, while the Review articles offer a point of view of some computer-driven techniques applied to drug research. Finally, the Perspective articles provide a vision of specific computational approaches with an outlook in the modern era of CADD.Computer-aided drug design (CADD) methodologies are playing an ever-increasing role in drug discovery that are critical in the cost-effective identification of promising drug candidates. These computational methods are relevant in limiting the use of animal models in pharmacological research, for aiding the rational design of novel and safe drug candidates, and for repositioning marketed drugs, supporting medicinal chemists and pharmacologists during the drug discovery trajectory. Within this field of research, we launched a Research Topic in de Bruyn Kops et al. reported the development and validation of GLORY, an innovative tool for predicting the metabolism of molecules, identifying chemical structures of metabolites formed by cytochrome P450 enzyme family (CYPs). The mentioned software combines two main ideas: a literature-based pool of CYP-mediated reaction rules and the site of metabolism (SoM) prediction. This approach is relevant since a tool for the in silico prediction of the metabolism of xenobiotic compounds can offer key information for developing novel chemical entities with improved metabolic stability . The GLORY web-server version is accessible at https://acm.zbh.uni-hamburg.de/glory/ . Montanari et al. described a computational approach for predicting potential toxicity of molecules taking into account transporter proteins. These latter proteins, expressed in the liver, are crucial in drug pharmacokinetics and are important constituents of the physiological bile flow and their inhibition could be relevant to the drug-induced liver toxicity. Using a comprehensive analysis of the publicly available data, a set of classification models was developed for predicting the inhibition of the transport for a set of liver transporters deemed relevant by different regulatory agencies. The models were computationally validated demonstrating an ability to predict the interaction profile of small molecules with liver transporters. These computational tools can assist medicinal chemists and toxicologists in prioritizing compounds at the initial steps of the development of drug candidates. The models are freely available as a web-service at https://livertox.univie.ac.at . Another work, regarding the pharmacological profiles of molecules, was presented by Sidorov et al.. They investigated the possibility to predict synergism of cancer drug combinations using NCI-ALMANAC data. This topic is of extreme interest since drug combinations could represent a promising strategy for treating cancer. The authors described an in silico approach to investigate drug combination synergy by exploiting the largest available dataset reporting synergism of anticancer drugs . Two machine learning (ML) procedures, Random Forest (RF), and Extreme Gradient Boosting (XGBoost), were employed on the selected dataset. The assessment of these computational tools indicated that the prediction of the synergy of undisclosed drug combinations is a feasible task. Accordingly, by using these kind of models it will be possible to significantly reduce the number of in vitro tests, by evaluating in silico which of the selected combinations are expected to be synergistic .Regarding the Original Research articles, two of them are related to innovative approaches concerning ADMET properties of the molecules. In particular, Velázquez-Libera et al. described a combined structure- and ligand-based approach for investigating the structural requirements governing the affinity of a series of molecules for the human Sigma1 receptor (S1R). This receptor represents a valuable drug target for treating neuropsychological disorders. The authors discovered an effective S1R agonist namely RC-33 as a promising neuroprotective agent. In the paper presented in this Research Topic, the authors computationally investigated the interactions of RC-33 and its novel derivatives within the S1R active site. To this end, different in silico techniques  were applied for investigating a potential mechanism of action of the developed compounds. The presented data could be useful for designing novel S1R modulators . Wu et al. also described a combination of different computational procedures (de novo protein structure prediction and ligand-protein interaction simulation) to investigate the structural requirements of compounds governing the affinity for the hSK2/calmodulin complex. The authors developed a homology model of SK2/calmodulin in order to predict potential binding sites. The ligand-protein interaction, using a series of computational procedures, was then investigated. The obtained results confirmed that the combination of different in silico techniques could facilitate the drug discovery process . Furthermore, some computational approaches, including 3D-QSAR, molecular docking, virtual screening (VS), ADME prediction, and molecular dynamics (MD), were used by Chen et al. to identify some HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs). Starting from a novel series of dihydrofuropyrimidine (DHPY) related compounds, endowed with antiviral activity, a computational investigation was performed employing 52 DHPYs. By applying sequential in silico methods, nine promising compounds were identified. These hit compounds could represent novel potential HIV-1 NNRTIs. Chen et al.. For identifying novel BCL-2 inhibitors from the Specs -SC- database, Tutumlu et al. employed multistep screening and filtering methods combining structure- and ligand-based techniques. The mentioned database was screened using a computational tool called “cancer-QSAR” and 26 toxicity QSAR models. The resulting non-toxic compounds were selected for two different target-driven approaches: (a) a molecular docking approach was applied to rank compounds considering their docking scores. Top-ranked compounds were employed in extensive MD simulations (100 ns) and biological assays; (b) the retrieved top-docking poses of each compound, derived from the subset selected by QSAR studies, were submitted to short MD simulations (1 ns), calculating their binding energies using the molecular mechanics generalized Born surface area (MM/GBSA) technique. By following this scheme, seven molecules were tested against different cancer cell lines. Four molecules were found to be able to reduce the proliferation of cancer cells, behaving as pro-apoptotic agents . The study performed by do Carmo et al. was also focused on BCL-2 and potential ligands based on a phenothiazine scaffold. The authors investigated some phenothiazines derivatives for their pro-apoptotic profile, performing an in silico study to relate their structures with their biological activities. By employing molecular docking simulation coupled to MD, the main interactions between compounds and the active site of the selected protein were highlighted. Notably, through these computational studies, the inhibition of BCL-2 by phenothiazines allowed for rationalizing the apoptosis-inducing effect on tumor cells .A relevant number of papers are focused on different ligand- and structure-based approaches or on a combination thereof to identify promising molecules for a given target. Accordingly, Naveja and Medina-Franco described a computational approach for selecting lead compounds from large datasets of chemical entities, acquired by high-throughput screening (HTS). They introduced the Constellation Plots as a general method for merging diverse and complementary molecular representations, to enhance the info contained in a visual representation and analysis of chemical space. This approach combines a sub-structure-based representation and classification of molecules with a “classical” coordinate-based representation of chemical space. A characteristic result of the mentioned technique is that organizing the molecules in analog series leads to the formation of groups of compounds, also known as “constellations,” in chemical space. Notably, this proposed method is useful in identifying, for example, insightful and “bright” Structure-Activity Relationships (StARs) in chemical space that are simple to interpret. The authors applied the developed method on two datasets of DNA methyltransferases (DNMTs) and AKT1 inhibitors (Naveja and Medina-Franco). Alberca et al. reported a computational approach that allowed for the repurposing of old drugs as antimalarial agents. The authors developed and experimentally validated a collection of ligand-based models that are able to identify falcipain-2 inhibitors. These models were used in a VS campaign, using two different databases (DrugBank and Sweetlead). The authors identified four potential hits to submit for biological evaluation. Among them, two drugs (odanacatib and methacycline) were confirmed as falcipain-2 inhibitors. Methacycline was found to be a non-competitive inhibitor of falcipain-2. Furthermore, the effects of both drugs on falcipain-2 hemoglobinase activity and on the growth of P. falciparum have been investigated . Baillif et al. reported a computational study, using a public dataset of compound-induced transcriptomic, for predicting the potential activity of compounds against 69 drug targets. The authors investigated the performances of the ML models constructed with transcriptomics data, with the computational tools generated by Morgan fingerprints. Active molecules against a given target could display comparable signatures in one or multiple cell lines, independent of the similarity in chemical structure, among the selected active chemical entities. For 25% of the tasks, RF computational tools employing transcriptomics signatures showed similar or better performances than those created by Morgan fingerprints. Compound-induced transcriptomic data offers a good chance for predicting targets based on cell response similarity, allowing to overcome the chemical space limitation of QSAR models . Shi et al. computationally investigated the SAR of some inhibitors of the dimerization process of PD-L1 by elucidating their potential binding and unbinding mechanism, using classical MD and metadynamics simulations. The contact analysis, R-group based QSAR analysis, and molecular docking provided additional insights about the SAR of these compounds. Accordingly, the outcomes of this research can be useful for optimizing compounds targeting PD-L1 . Liu et al. introduced two methods for improving the selection of active molecules by using similarity information of all compounds. One technique ranks a molecule considering its highest z-score as an alternative of its highest Tanimoto index, while the other method ranks compounds by calculating an aggregated score taking into account their Tanimoto similarity related to all identified active and inactive molecules. These evaluations, performed using datasets available from PubChem, belonging to over 20 HTS studies, suggested that both approaches accomplished a ~10% higher Boltzmann-enhanced discrimination of receiver operating characteristic (BEDROC) score, compared to the classical approaches. Interestingly, the presented methods could offer an enhancement in early recognition of lead compounds during VS campaigns . Lima et al. presented a computational approach for finding multi-kinase inhibitors against Plasmodium falciparum calcium-dependent protein kinases 1/ 4  and protein kinase 6 (PK6), in order to select novel multi-target compounds as antimalarials. By using shape-based and ML models, employing chemical databases of drug-like compounds, the authors identified 10 hit compounds to submit for biological evaluation. Among them, LabMol-171, LabMol-172, and LabMol-181 behaved as nanomolar antiplasmodial agents. Furthermore, LabMol-171 and LabMol-181 also inhibited P. berghei ookinete development, representing novel transmission-blocking agents . Bühlmann and Reymond reported an approach to address the limitation of the GDB17 database (166.4 billion molecules), which contains numerous molecules that are too complex to synthesize. To this end, the authors developed the GDBChEMBL database, a small set of GDB17, which consists of 10 million molecules identified by means of the calculation of their ChEMBL-likeness score (CLscore). This subset contains compounds with higher synthetic accessibility, maintaining a comprehensive coverage of chemical space distinctive of the GDB17 database. GDBChEMBL is downloadable from http://gdb.unibe.ch; interactive chemical space map: http://faerun.gdb.tools (Bühlmann and Reymond).Sirous et al. developed and experimentally validated an in silico procedure useful for hit-to-lead optimization. In particular, from micromolar HIV integrase (HIV IN) inhibitors, the authors described a computational workflow based on an in silico structure-based combinatorial library designing technique. The mentioned methodology is useful for combining the design of a combinatorial library and side-chain hopping with Quantum Polarized Ligand Docking (QPLD) and MD simulations. This method indicated the most valuable decorations for a promising scaffold. From this final set of optimized molecules, three representative compounds were synthesized and evaluated by in vitro tests. Among them, one compound was found to be an effective inhibitor of HIV IN in the low nanomolar range. Moreover, the biological characterization of the molecule showed that this compound is able to inhibit HIV-1 replication and HIV-1 IN strand transfer activity, with potency comparable to that found for Raltegravir . Ferreira et al. presented an article describing the development of cyclic imides as inhibitors of cruzain, a validated drug target of Trypanosoma cruzi. By using a micromolar-range cruzain inhibitor, the in silico optimization scheme led to the development of a non-toxic inhibitor of T. cruzi intracellular amastigotes in the nanomolar-range. By following the mentioned procedure, the authors identified a protocol useful for the rational design of novel trypanocidal agents targeting the cruzain enzyme . Pallante et al. proposed a computational approach based on different in silico techniques such as homology modeling, molecular docking, and MD for investigating the interactions between several novel colchicine derivatives and tubulin isotype βIII. These derivatives were screened and ranked considering their binding affinity and conformational stability in the colchicine binding site. This study could be extremely relevant for rationally designing novel colchicine-based compounds as effective anticancer agents . Pavlin et al. focused their research article on the application and experimental validation of a VS protocol to identify small molecules that are able to target a particular variant of estrogen receptor alpha (ERα Y357S) that confers endocrine resistance, disease relapse, and increased mortality rates in patients affected by ER-positive breast cancer. By applying a VS procedure for screening different commercial databases, the authors identified five compounds active on recurrent Y537S ERα polymorphism in MCF7, and MDA-MB-231 breast cancer cell lines. Among the identified compounds, one of them showed selectivity for Y537S ERα, exhibiting no toxicity against breast cells. Remarkably, 4.5 μs of biased and unbiased MD was used for investigating the structural, thermodynamics, and the kinetics of these active ligands against wild type and diverse ERα variants . The information provided by the mentioned study could be relevant for discovering mutant specific drug-candidates for improving breast cancer therapies . Quan et al. investigated novel quinoline derivatives as P-glycoprotein (P-gp) inhibitors useful for counteracting the multidrug resistance, which represents a significant cause of cancer treatment failure. Among the mentioned derivatives, YS-7a was proposed as the most promising P-gp inhibitor. YS-7a blocked the P-gp transport without influencing the P-gp expression. Furthermore, YS-7a promoted the ATPase activity of P-gp in a dose-dependent manner. This compound could represent a valid starting point for developing novel derivatives that are able to treat multidrug resistant cancers .Michel et al., using different web-servers  and a commercial tool (Schrödinger's SiteMap), comprehensively predicted ligand binding cavities, druggability scores, and conformationally active regions of the nucleoside diphosphates attached to the sequence-x (NUDIX) hydrolase protein family. Subsequently, a molecular docking study, employing Glide software, was carried out to assess the affinity of a subset of the ZINC FragNow database for the identified potential binding sites. This preliminary dual ranking, of druggable sites within the NUDIX protein family, was then compared with experimental hit rates acquired from biological studies. The detected correlation indicated that the described workflow could represent a valuable protocol for prioritizing targets and for excluding them in VS approaches . Michel et al. presented a sequence-to-structure-based methodology for predicting drug resistance. The developed workflow produced and compared Molecular Interaction Fields (MIF), mapping the areas of energetically favorable interactions, between numerous chemical probes and the target active site. The technique appears to be appropriate for understanding changes of the three-dimensional structures and the physicochemical environment caused by mutations affecting the target active site. This approach was applied to four datasets of known HIV-1 protease sequences, displaying that it is able to correctly classify resistant and susceptible sequences given as the input. The described study is a novel step for interpreting the influence of genetic variability on the response to HIV 1 treatments . Sánchez-Tejeda et al. proposed a vector analysis for measuring and defining “multitargeticity.” The research on multi-target drugs could be relevant for identifying therapeutic agents to treat multifaceted diseases. The authors, considering the order and force of a ligand, described two “multi-target” indexes namely, 1 and 2. By combining the mentioned indexes, it is possible to discriminate multi-target drugs. These indexes were used for screening a chemical library of potential ligands that possess an affinity for diverse targets involved in multiple sclerosis. The application of the protocol allowed the identification of 10 molecules that could represent potential lead compounds for developing multi-target drugs . Bissaro et al. applied the SuMD technique to ribonucleotide targets of pharmacological interest. SuMD is a modified MD protocol for accelerating the sampling of molecular recognition steps on a nanosecond timescale. Interestingly, they demonstrated the methodological ability of SuMD to reproduce the binding mode of viral or prokaryotic ribonucleic complexes and artificially engineered aptamers with a remarkable accuracy .Cavasotto and Aucar proposed a new approach for scoring results obtained from high-throughput docking (HTD) approaches. For better characterizing protein-ligand interactions, the authors proposed a quantum mechanical (QM)-based docking scoring function in order to obtain more accurate HTD results. This novel technique was investigated using 10 different drug targets belonging to various families with diverse binding site features. The output clearly demonstrated that the application of the QM scoring function could improve the performance of HTD methods (Cavasotto and Aucar). Pinto et al. presented a novel screening software, namely, CaverDock. In particular, the authors focused their studies on protein tunnels and channels that could represent promising drug targets. In fact, compounds able to hinder the entrance of substrates or release of products could be considered effective modulators of the biological activity. To this end, the influence of rigid and flexible side-chains on various substrates and inhibitors of seven unrelated drug targets was assessed. The accuracy of the software was evaluated by comparing the data found by CaverDock with experimental results obtained for the heat shock protein 90α. As a final point, CaverDock was used in a VS campaign employing anti-inflammatory and anticancer FDA-approved drugs against two drug targets . The analysis of the potential energies of binding and unbinding trajectories allowed for identifying functional tunnels. Accordingly, the presented software is a valuable computational resource useful in VS campaigns. CaverDock is accessible from https://loschmidt.chemi.muni.cz/caverdock/; web https://loschmidt.chemi.muni.cz/caverweb/ . Yuan et al. presented LigBuilder-V3, a software for de novo multi-target drug design. This computational tool can be useful for rationally designing and optimizing molecules with multi-target profiles. For validating the computational approach, LigBuilder-V3 was employed to design inhibitors that are able to target HIV protease and HIV RT, employing three different approaches. The resulting molecules, assessed by MM/GBSA, behaved as potential inhibitors for the selected drug targets. The software can be found at http://www.pkumdl.cn/ligbuilder3/ .Rastelli and Pinzi focused the attention on the need to obtain a valid post-docking analysis in VS campaigns. In fact, nowadays, HTD is a valuable in silico methodology extremely useful for rapidly identifying hit compounds for a given target. Unfortunately, HTD has some weaknesses , making docking outputs inevitably approximate. So, post-docking analyses are required to overcome these mentioned issues. The authors proposed a comprehensive method for the post-docking analysis in VS approaches, developing BEAR (Binding Estimation After Refinement), a post-docking resource this is able to refine docking poses employing MD, and re-scores ligands using (MM/PB(GB)SA). The article provides a rational perspective about the introduction of more accurate refinement and rescoring approaches in VS to provide more reliable results (Rastelli and Pinzi). In the second Perspective article, Vásquez and González Barrios investigated the ligand efficiency (LE) metrics and how to improve it for an efficient and reliable hit identification in CADD. LE is still employed as a decision-making criteria in CADD. Furthermore, in fragment-based drug discovery (FBDD), LE metrics are extremely efficient in selecting promising “core” fragments for optimization. The authors presented a relative group contribution (RGC) model for improving FBDD. Accordingly, this approach could be useful in virtual fragment-based screening studies (Vásquez and González Barrios).In this Research Topic two Perspective articles have been published. In the first article, Santos et al. discussed the use of Molecular Mechanics (MM) for describing protein-ligand interactions. The authors reported a case study on the halogen bonds (XBs). Although less efficient than hydrogen bonds (HB), XBs were found to be relevant in CADD. XBs are able to improve the affinity and selectivity of a molecule against a potential drug target. Due to the limited ability of MM techniques to describe XBs, the authors indicated that a parametrization of the force-fields equations could be considered for improving the definition of XBs. This review highlighted some suggestions for parametrizing force-fields to accomplish reliable outcomes of complex non-covalent interactions . Gagic et al. reviewed the in silico approaches employed for designing compounds behaving as kinase inhibitors. Kinases are pivotal in designing anticancer agents. They discussed and compared, considering some representative case studies, different methods such as pharmacophore modeling, MD, VS, and molecular docking for the rational design of kinase inhibitors . de Souza Neto et al. proposed a Review article for outlining the FBDD strategies exploring numerous computational strategies to apply for fragment-to-lead optimization. They considered potential fragment expansion strategies such as hot spot analysis, druggability prediction, SAR, application of ML/deep learning (DL) models for VS and some de novo approaches for suggesting synthesizable novel molecules. Moreover, the authors highlighted some recent case studies in FBDD, and how computational approaches were successfully used for developing lead compounds . Maia et al. presented a Review article which reported a comprehensive outlook on the tasks in CADD for performing structure-based VS (SBVS). The authors compared methods and tools for SBVS employed in the modern drug development trajectory . Thafar et al. discussed some established techniques using artificial intelligence (AI), ML, and DL approaches for identifying drug-target interactions (DTIs) and for predicting drug-target binding affinities (DTBA). This Review article reported an inclusive summary about the computational approaches for predicting DTBA. Notably, this review performed the first inclusive comparison analysis of in silico tools focused on DTBA related to AI/ML/DL .Finally, five Review articles reported a critical discussion about different computational approaches in various CADD fields. https://www.frontiersin.org/research-topics/10032/in-silico-methods-for-drug-design-and-discovery.In summary, as Guest Editors, we would like to thank all the authors and co-authors for their important contributions to this Research Topic, all the reviewers for their valuable work in evaluating the submitted manuscripts, and the editorial staff of Frontiers for their kind continued assistance. Taken together all these combined efforts allowed for the great success of this Research Topic. We expect this topic to contribute to the advancement of drug design and discovery and believe it serves as a valuable source of information and inspiration to scientists and students. The Research Topic is freely accessible through the following link All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The association between a preceding malignancy and the onset of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been reported in several studies. While the co-existence of ANCA and anti-glomerular basement membrane (GBM) antibodies in an individual patient is not a common occurrence, this double-positive disease currently has no optimal treatment method. Herein, we report a case of a double-positive disease involving the sequential development of acute kidney injury (AKI) and diffuse alveolar hemorrhage (DAH) in a patient with small cell lung cancer (SCLC).A 75-year-old Japanese woman was diagnosed with small cell lung cancer (cT3N2M1b cStage IV) and received chemotherapy. After one cycle of chemotherapy, she experienced fever and malaise. Her serum creatinine level rapidly increased, and she tested positive for myeloperoxidase (MPO)-ANCA and anti-GBM antibody. She was diagnosed with AKI due to microscopic polyangiitis (MPA) based on renal biopsy. Corticosteroid therapy was initiated, which improved her renal dysfunction. Eight days after she was discharged from the hospital, she complained of dyspnea and bloody sputum, and her condition rapidly progressed to respiratory failure. Upon chest imaging, ground-glass opacities were seen in her bilateral lower lungs. Laboratory examinations after admission revealed a lower MPO-ANCA titer and an elevated anti-GBM antibody titer compared to her previous admission. We diagnosed her with DAH due to an anti-GBM disease. After corticosteroid pulse therapy, plasma exchange was performed five times; her oxygen saturation and chest radiologic findings improved gradually. Following five cycles of plasma exchange, her oxygen saturation recovered to 95% in room air.To our knowledge, this is the first reported case of vasculitis caused by MPA and anti-GBM disease leading to the development of AKI and DAH during treatment of SCLC. SCLC, MPA, and anti-GBM disease may occur sequentially. A double-positive disease might have a worse prognosis; therefore, intensive therapy is more likely to achieve a better outcome. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including microscopic polyangiitis (MPA), comprise small- to medium-vessel vasculitides that affect multiple organs and are life-threating when untreated . Anti-glCo-presentation of ANCA and anti-GBM antibodies is not uncommon. Between 7 and 41% of patients with anti-GBM disease also test positive for ANCA at the time of diagnosis, and it is more common in the elderly , 4. SeveIn some cases of AAV, malignancy may play a critical role in triggering the vasculitic process. A recent meta-analysis showed that AAV was associated with an increased risk of cancer, with a standardized incidence ratio of 1.74. However, the relationship between AAV and malignancies remains controversial . CurrentA 75-year-old Japanese woman presented to another hospital with a fever in August 2018. Chest x-ray and computed tomography (CT) showed a mass in her lower right lobe. She was suspected to have a lung abscess and was treated with antibiotics, but her fever was sustained. Thus, she presented to our hospital for further investigation. Her past medical history included chronic obstructive pulmonary disease and hypertension. She had smoked approximately two packs of cigarettes a day for 53 years and had quit smoking 2 years ago. She was taking theophylline, vonoprazan, amlodipine, and tiotropium bromide hydrate/olodaterol hydrochloride. We conducted bronchoscopy and diagnosed her with SCLC . She was administered carboplatin and etoposide and was discharged.Four days after the discharge, she had fever and malaise; her serum C-reactive protein (CRP) was elevated at 11.4 mg/dl. She was re-admitted and treated with antibiotics. The main laboratory results from the second admission are shown in Table Only 7 days after the second discharge, the patient complained of dyspnea and returned to our emergency department. On physical examination, her blood pressure was 146/84 mmHg; she had a pulse rate of 108 beats per minute, respiratory rate of 24 breaths per minute, and oxygen saturation of 85% on 10 l/min of oxygen via non-rebreather mask. On chest auscultation, coarse crackles were bilaterally detected in the lower back. Chest x-ray and CT showed ground-glass opacities in the bilateral lower lung fields , whereas the survival rate with immunosuppressive drugs alone is only 53% (9 of 17 patients) .In the present case, the patient was positive for both MPO-ANCA and anti-GBM antibody at the time of AKI diagnosis. Since immunofluorescence of the kidney biopsy demonstrated no linear deposition of IgG along the glomerular capillaries, we diagnosed the patient with MPA alone rather than complicated by anti-GBM disease and initiated only corticosteroid therapy. Although the renal dysfunction and high MPO-ANCA titer immediately improved, DAH sequentially occurred in parallel with an increased titer of anti-GBM antibody. Taking into account this clinical course and the double-positive disease, we should have initiated treatment with both immunosuppressive drugs and PE at the time of AKI diagnosis.et al. reported that AAV increased the risk of concurrent or preceding malignancy [Our patient sequentially developed MPA and anti-GBM disease after the diagnosis of SCLC. At the time of her SCLC diagnosis, the MPO-ANCA and anti-GBM antibody titers were not measured, as there were no clinical findings suggestive of MPA or anti-GBM disease. The relationship between vasculitis and malignancy remains unclear and controversial. The association between a preceding malignancy and the onset of AAV has been investigated in several studies. A retrospective study showed that the overall risk for malignancy prior to AAV diagnosis was similar to that of the general population . On the lignancy . The inclignancy .Some pathogenic mechanisms have been postulated to explain the association between vasculitis and malignancy. Tumor cells may cause immunologic reactions against the vascular endothelium, release various cytokines causing endothelial injury, induce delayed hypersensitivity reaction by the deposition of tumor proteins on vessel walls, produce critical levels of circulating immune complexes that injure the endothelial cells of post-capillary venules, and so on. .According to our research, there are no previous reports of SCLC preceding AAV or anti-GBM disease. Additionally, the association between malignancy and anti-GBM disease has never been reported. Lung cancer, especially SCLC, is sometimes associated with paraneoplastic syndromes. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators from tumor cells, such as hormones and hormone-like peptides, cytokines, and antibodies . In thisIn conclusion, we present a rare case of a double-positive disease involving the sequential development of AKI and DAH in a patient with SCLC. The key message from this case report is that lung cancer, MPA, and anti-GBM disease might be closely associated in terms of their pathogenesis and manifestation. Additionally, patients with double-positive diseases may develop AKI and DAH more frequently (like anti-GBM disease) rather than AAV alone. The administration of immunosuppressive drugs plus PE at the time of diagnosis of double-positive disease may lead to better outcomes. Further studies are needed to validate these speculations.


Background: The benefit of blood cholesterol reduction for secondary prevention of ischemic stroke remains undetermined in Chinese patients. The purpose of this meta-analysis was to determine whether lipid-lowering agents including statins, fibrates, nicotinic acid, and ezetimibe reduced the risk of recurrent stroke in ischemic stroke patients in China and whether such findings could inform treatment decisions for blood lipid-lowering treatment in China.Methods: The English electronic databases PubMed, EMBASE, Cochrane Library and Chinese databases CNKI, Sino-Med, Wan Fang, and VIP were searched for studies published between January 1990 and April 2020. This meta-analysis included published data from trials that randomly assigned patients to groups treated with either blood lipid-lowering regimens or placebo. Effect comparisons were made using fixed effects model in meta-analysis and linear and spline regression were performed to identify the relative risk of stroke recurrence. The primary outcome was the reduction of total ischemic stroke events, and relative risk values were obtained using a risk prediction equation developed from the control groups of the included trials.Results: Five studies including 4,999 individuals with available data met the inclusion criteria. Relative to the control groups, the pooled estimated odds ratio (OR) for recurrent stroke among those who received lipid-lowering therapy was 0.79 . A 50% or greater reduction in low-density lipoprotein cholesterol (LDL-C) significantly reduced the risk of ischemic stroke recurrence (OR: 0.15 [95% CI: 0.11–0.20]). The overall beneficial effect of statin therapy was confirmed to prevent ischemic stroke with an OR of 0.51 (95% CI: 0.36–0.72).Conclusions: Effective lipid-lowering therapy could decrease the blood LDL-C level, which had a protective effect against stroke recurrence. These results support the use of predicted baseline cerebrovascular disease risk equations to inform decisions regarding blood lipid-lowering treatment in ischemic stroke patients in China. Ischemic stroke is the most common neurological disease in the elderly population . In ChinDysfunctional blood lipid metabolism typically involves increased levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL) and may also involve decreased high-density lipoprotein cholesterol (HDL) levels . The 5-yTherefore, here we review the relationship between blood lipid levels, lipid-lowering therapies, and ischemic stroke recurrence in Chinese patients in order to provide insight for the effective use of lipid-lowering therapy for secondary stroke prevention.The PubMed, EMBASE, and Cochrane Library were searched along with the Chinese electronic databases CNKI, Sino-Med, Wan Fang, and VIP for studies published between January 1990 and April 2020. The language was restricted to English and Chinese. The search terms were “hypercholesterolemia,” “dyslipidemia,” “cholesterol,” “low-density lipoprotein,” and “stroke.”The PICO  model was used to define the clinical question for this systematic review and identify appropriate studies with clinical evidence in the literature . The folTwo reviewers screened the articles according to the inclusion and exclusion criteria independently. A third reviewer verified the data, and any inconsistency was resolved by discussion. The recorded data included characteristics of the study and the participants, details of the lipid-lowering regimens used, lipid levels before and after treatment, outcome events, and differences in outcome data between the intervention and control groups. This meta-analysis was performed according to the Preferred Reporting Instructions for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality assessment for studies of diagnostic accuracy (QUADAS) was applied to determine the methodological quality of the included studies , 16.Q value and I2 test. Pooled odds ratios (ORs) were calculated as an indicator of the weighted pooled risk under the fixed effects model. Briefly, the OR reflects the number of participants in a group who achieved a stated end-point divided by the number of patients who did not. Linear and spline regression were performed to determine the association between the LDL-C level and the relative risk of stroke recurrence. To mitigate heterogeneity, random effects models were adopted instead of fixed effects models.Stata 14.0 and Review Manager 5.3 were employed for all data analyses. The significance level was set at α = 0.05. Heterogeneity across studies was evaluated according to the Cochran-via Begger's test to assess publication bias among the included studies, with asymmetry of the plot considered indicative of publication bias. This method is based on scatter plots of the treatment effect estimated by individual studies vs. a measure of study size or precision. In this graphical representation, larger and more precise studies are plotted at the top, near the combined effect size, while smaller and less precise studies show a wider distribution below .–22.18–22I2 = 74.6%, P for heterogeneity = 0.003). On random effects analysis, the pooled relative risk with lipid-lowing treatment was 0.79  study was the first clinical trial of statin lipid-lowering therapy for secondary prevention of stroke, and it included study population of 4,731 patients with a primary endpoint of fatal vs. non-fatal stroke and secondary end points of transient ischemic attack and other coronary events , 26. TheIn addition to lifestyle changes, one of the important ways to reduce the risk of ischemic stroke is to lower cholesterol levels. As one of most effective lipid-lowering medications, statins are severely inadequately used in patients with ischemic stroke in China, and the standards for drug safety need to be improved . The preOur results indicate that a >50% reduction in the LDL-C level significantly reduced the risk of ischemic stroke recurrence. In the prevention and treatment of ischemic stroke, the intensity of lipid-regulating therapy is important, especially as statins not only reduce the LDL-C level but also atherosclerotic plaque , 30. MorA consensus has yet to be reached regarding the relationship between dyslipidemia and the recurrence of ischemic stroke, and the standards for lipid abnormalities have varied among studies, limiting the ability to compare their results. In addition, most recent studies have been clinical trials or retrospective analyses, which have certain limitations. Therefore, large-scale, multi-center prospective studies are needed to further clarify the relationship between blood lipid management and ischemic stroke recurrence.K-NC, LH, L-MZ, Y-QR, and YL conceived and designed the research. K-NC, LH, and L-MZ collected data and conducted the research. K-NC and L-MZ analyzed and interpreted data. K-NC and LH wrote the initial paper. K-NC, Y-QR, and YL revised the paper. K-NC had primary responsibility for final content. All authors read and approved the final manuscript.Y-QR and YL are employees of MSD China Holding Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This study aimed to explore whether African American/Black and Hispanic/Latino adolescents are being asked about electronic cigarette (e-cigarette) use (vaping) and advised not to use them.N = 362) with no vaping history, self-identified as African American/Black and/or Hispanic/Latino, and able to read and speak English and/or Spanish were recruited through partner schools and community-based organizations. Participants completed a survey reporting sociodemographic characteristics  and they were asked about e-cigarette use and/or were advised not to use them by a health professional.In 2021, adolescents (p = 0.009) and advised not to use them . Moreover, compared to African American/Black participants, Hispanic/Latino participants were significantly less likely to be advised not to use e-cigarettes . Furthermore, compared to male participants, female participants were significantly less likely to be advised not to use e-cigarettes .In total, 12% of African American/Black and 5% of Hispanic/Latino participants reported not seeing a health professional in the year prior to enrollment. Of the participants who reported visiting a health professional, 50.8% reported being asked and advised about vaping. Over one-quarter (28.4%) of participants were neither asked nor advised regarding vaping. Compared to English-speaking participants, Spanish-speaking participants were significantly less likely to be asked about e-cigarette use (45.2 vs. 63.9%, Compared to English-speaking participants, Spanish-speaking participants were significantly less likely to self-report being asked about e-cigarette use and advised not to use them. Moreover, Hispanic/Latino and female adolescents were significantly less likely to self-report being advised not to use e-cigarettes compared to their Black/African American and male counterparts. Future research is needed to improve health professional attention toward asking about and advising against vaping among adolescents. Since 2014, electronic cigarettes (e-cigarettes) have been the most commonly used nicotine and tobacco product among middle and high school students in the United States (U.S.) , lung inRoutine healthcare visits provide an opportunity to address vaping among adolescents. The Ask, Advise, and Refer (AAR) model is a well-established approach for health professionals worldwide to address nicotine and tobacco use among patients, including adolescents . The AARThis study is a secondary data analysis of a randomized controlled trial (RCT) designed to assess the immediate impact of vaping prevention graphic messages on the susceptibility of future vaping among Black and Latino adolescents , 12. TheIn 2021, Black and Latino adolescents were recruited by a team of diverse, bilingual (English and Spanish), trained recruiters using proactive and reactive strategies. Adolescents aged 12–17 years with no history of e-cigarette use who self-identified as African American/Black and/or Hispanic/Latino and able to read and speak English and/or Spanish were included in the RCT. Parents'/guardians' permission and adolescents' assent were obtained from all subjects involved in the study. Details and results of the recruitment, eligibility, and permission/assent have been reported in a previous publication . ParticiAll assessments described in this study were completed in the language of preference of the participant, either English or Spanish, at baseline. The baseline survey collected information on demographics . The baseline survey also assessed whether participants were being asked if they use e-cigarettes and/or advised not to use them. Questions included “Think about when you have visited a doctor, dentist, nurse, or other health professional in the past 12 months. During any of these visits, were you asked if you use e-cigarettes?” and “Think about when you have visited a doctor, dentist, nurse, or other health professional in the past 12 months. Were you given advice not to use any e-cigarettes?” . Answer t-test was used for continuous variables. Significant associations with being asked and/or advised about e-cigarette use (at the p < 0.05 level) were tested in an unadjusted logistic regression model, followed by a logistic regression model that adjusted for all significant associations. Analyses were conducted using Stata 15.0.For this study, participants who reported having not seen a health professional in the past 12 months were not included in the analyses. Sociodemographic characteristics of participants were described between those who were and were not asked about e-cigarette use and among those who were and were not advised about vaping. Fisher's exact test was used to compare proportions in categorical variables and crude odds ratios (OR) were reported. Student's N = 362), 13.6% (n = 22) of African American/Black and 5.6% (n = 9) of Hispanic/Latino participants reported not having seen a health professional in the 12 months prior to enrollment. Of the participants who reported visiting a health professional in the past 12 months (n = 331), half (50.8%) reported both being asked and advised about e-cigarette use. An additional 20.9% of participants were either asked or advised. Over one-quarter of participants (28.4%) were neither asked nor advised regarding e-cigarette use.At baseline (p = 0.009) or advised  about e-cigarette use compared to primarily English-speaking Hispanic/Latino participants. Compared to African American/Black participants, Hispanic/Latino participants were less likely to be advised about e-cigarette use . Overall, female participants were less likely to be advised about e-cigarette use compared to male participants , with Spanish-speaking adolescents self-reported as being significantly less likely to be asked  and advised  about e-cigarette use in comparison to English-speaking adolescents. Similarly, female participants remained significantly less likely to be advised about e-cigarette use by a health professional when compared to male participants . Finally, Hispanic/Latino adolescents were significantly less likely to be advised relative to African American/Black adolescents  whether African American/Black and Hispanic/Latino adolescents are being asked whether they use e-cigarettes and/or advised not to use them and (2) the unique associations of being asked and/or advised about vaping with sociodemographic characteristics. In this study, only half of the adolescents who reported having seen a health professional within the previous year self-reported being both asked and advised about e-cigarette use. Furthermore, one-quarter of the participants were neither asked nor advised regarding e-cigarette use. Primarily Spanish-speaking adolescents self-reported significantly lower rates of being asked and advised about e-cigarette use during healthcare visits when compared to English-speaking adolescents. This difference persisted even after controlling for significant associations with being asked and/or advised about e-cigarette use. Additionally, Hispanic/Latino and female participants self-reported lower rates of being advised about e-cigarette use in comparison to African American/Black and male participants, respectively.There are many possible factors contributing to this low rate of addressing e-cigarette use at healthcare visits. Electronic health record tools have the potential to assist with reminding health professionals to address smoking and vaping among adolescents. However, the use of these tools remains low, with a 2019 study finding that, on review of 518 adolescent well visits, none documented assessment of e-cigarette use . MoreoveOur study showed that female participants did not significantly differ from male participants in the likelihood of being asked about e-cigarette use. However, female participants were significantly less likely to be advised against e-cigarette use when compared to male participants. One possible reason for this observed difference is that health professionals may perceive that vaping is higher among male adolescents compared to their female counterparts. However, according to the 2022 U.S. National Youth Tobacco Survey, the prevalence of current vaping is higher among female adolescents compared to male adolescents  . AdditioSpanish-speaking adolescents in this study were significantly less likely to be asked or advised about e-cigarette use in comparison to English-speaking adolescents. Language barriers and poor access to or quality of translation services have previously been identified as significant factors contributing to reduced smoking cessation support provided to Spanish-speaking Latino patients . These fThere are several limitations to this study. First, data are self-reported, and there is a possibility that participants felt compelled to offer socially desirable responses or did not remember whether they were asked and/or advised about vaping. Second, the study did not assess who asked and/or advised the adolescent about vaping . This information could guide future-targeted interventions to increase the AAR model. Third, given that this study focused on adolescents who have not vaped, we did not assess whether participants were referred—the third pillar of the AAR model—to vaping cessation resources. Fourth, the exclusion of adolescents who did not self-identify as African American/Black and/or Hispanic/Latino  prevented the study from shining light on other potential racial and ethnic disparities. Lastly, this is a non-probability sample of African American/Black and Hispanic/Latino adolescents which limits generalizability to the broader population of Black and Latino adolescents.In this study, compared to English-speaking participants, Spanish-speaking participants were significantly less likely to self-report being asked about e-cigarette use and advised not to use them. Moreover, Hispanic/Latino and female adolescents were significantly less likely to self-report being advised not to use e-cigarettes compared to their Black/African American and male counterparts. Future research is needed to improve health professionals' attention to asking about and advising against vaping among adolescents.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by University of Rochester Medical Center. Written informed consent for participation was not provided by the participants' legal guardians/next of kin because: Parents'/guardians' permission and adolescents' assent were obtained from all subjects involved in the study.MC, DC, SM, DO, AC, and FC-B: conceptualization. PR-P and XC: formal analysis. RO: project administration. MC, DC, and FC-B: writing—original draft preparation. PR-P, XC, BH, RO, MR, KW, DL, SM, DO, and AC: writing, reviewing, and editing. All authors have read and agreed to the published version of the manuscript.


The RUT was statistically highly associated with trauma cases . In an analysis that categorized cases by region, a statistically higher proportion of transportation was used in island regions . More RUT was associated with non-island regions . (4) Conclusions: The tele-emergency system had a great role in reducing unnecessary patient transportation in non-severe trauma cases and non-island rural area emergency cases. Further research is needed for a cost/benefit analysis and clinical outcomes.(1) Background: The government of South Korea has established a nationwide web- and mobile-based emergency teleconsultation network by designating urban and rural hospitals. The purpose of this study is to analyze the characteristics and effectiveness of the tele-emergency system in South Korea. (2) Methods: Tele-emergency consultation cases from May 2015 to December 2018 were analyzed in the present study. The definition of a tele-emergency in the present study is an emergency consultation between doctors in rural and urban hospitals via a web- and mobile-based remote emergency consultation system (RECS). Consultations through an RECS are grouped into three categories: medical procedure or treatment guidance, image interpretation, and transportation requests. The present study analyzed the characteristics of the tele-emergency system and the reduction in unnecessary transportation (RUT). (3) Results: A total of 2604 cases were analyzed in the present study from 2985 tele-emergency consultation cases. A total of 381 cases were excluded for missing data. Consultations for image interpretation were the most common in trauma cases (71.3%), while transfer requests were the most common in non-trauma cases (50.3%). Trauma patients were more frequently admitted to rural hospitals or discharged and followed up with at rural hospitals (20.3% vs. 40.5%) after consultations. In terms of disease severity, non-severe cases were statistically higher in trauma cases (80.6% vs. 59.4%;  Tele-emergency services are defined as remote-care medical services for acute illness, injury, and the acute exacerbation of chronic disease, including initial evaluations, diagnoses, treatments, the coordination of care, and disposition ,3,4,5,6.After the COVID-19 pandemic, medical and social environments have changed significantly. This worldwide outbreak led to a transformation in healthcare environments, from healthcare professionals’ clinical infection control protocols to whole emergency medical service systems ,12,13,14Unlike chronic diseases, emergency diseases or injuries require rapid diagnoses and urgent management, which have a significant impact on patients’ clinical prognoses. In emergency medicine, it is critical to provide high-quality healthcare service to patients, without any interference from regional, environmental, or socioeconomic factors. Various methods have been attempted to provide medical services to vulnerable areas, and information-technology-based emergency teleconsultations between rural and urban hospitals have been developed and studied to provide emergency medical services to vulnerable areas as one solution ,26,27,28In South Korea, the Ministry of Health and Welfare has directed the step-wise development of the nationwide emergency teleconsultation network since 2015, designating urban and rural hospitals. Tele-emergency systems have been in operation to provide emergency medical services to vulnerable areas by using remote emergency consultation systems (RECSs). A RECS is a web- and mobile-based designed tele-emergency consultation system and provides high accessibility and portability. This property makes it highly suitable for emergency or critical consultation environments. Additionally, its cloud-based architecture provides an advantage for initial system setup, management, and maintenance, especially in rural regions.There have been some previous studies analyzing the outcomes and benefits of teleconsultations of specific diseases or regions, but research on emergency consultations regardless of a specific disease, injury, or region with easily accessible and expandable and web- and mobile-based tele-emergency systems is lacking.The present study aims to analyze the characteristics and effectiveness of nationwide web- and mobile-based tele-emergency consultation cases performed between rural and urban hospitals in South Korea.South Korea is a peninsula surrounded by the sea on three sides, with 3170 islands of varying sizes . VariousFor emergency teleconsultations, a specific modality is needed for healthcare professionals at rural and urban hospitals for the management of patients’ medical status. A remote emergency consultation system (RECS) has been developed for video and voice transmissions and the sharing of patients’ medical status between healthcare professionals. The RECS is designed for particular functions, such as providing an electronic medical record (EMR) with cloud-based architecture. RECSs allow healthcare professionals to access a central server via the internet to send, store, and download patients’ clinical information, including web- and mobile-based picture archiving and communication systems (PACSs) with encrypted data transmission through SSL VPNs  or IPsec VPNs . Patient clinical data that are collected from various diagnostic medical devices and transmitted via internet communication networks depend on region and network infrastructure. Urban and some rural areas mainly used fiber-to-the-home (FTTH) networks with speeds up to 10 Gbps, and in rural and island areas, long-term evolution (LTE) with speeds up to 100 Mbps or 3G (Third Generation) HSPA(High-Speed Packet Access) with a maximum of 14 Mbps are used. Satellite communication with a bandwidth of 1 Mbps to 2 Mbps is used in cases at sea or for patient transportation by boat . HealthcThe tele-emergency system in this study is defined as a medical service for emergency teleconsultations between doctors in a rural hospital and an urban hospital using the RECS. The urban hospital is mainly a tertiary hospital or regional emergency medical center designated by the government which has emergency teleconsultation capacity, including facility, equipment, and medical staff. The rural hospital is a medical institution or healthcare center located in a vulnerable area that has entered into a tele-emergency network participation agreement with an urban hospital and the government.www.recs.nemc.kr, accessed on 18 August 2023). Authorized approval from the National Emergency Medical Center under the Ministry of Health and Welfare is needed to access RECS. Users can download the mobile application of RECS  to their smartphones from the RECS website. After logging into the RECS via web or mobile application, healthcare professionals can request or respond to consultations and can review patients’ clinical information.Healthcare professionals from hospitals designated on the tele-emergency network can access RECS version 2.0  by visiting the RECS web page , etc. Radiologic images are uploaded through Web a PACS connected to RECS.In the consultation response process, the doctor can access the page of the patient requestion the consultation by clicking on the patient list. On individual patient pages, urban hospital doctors can access uploaded patients’ clinical information medical data and radiologic images. Then, based on a patient’s clinical condition, they can record a consultation answer and recommendation appropriate to the reason for consultation. If a video consultation is needed, the doctor can initiate a video conference through the “video tell” option in the top right corner of the RECS page or the camera icon of the mobile application. The mobile application of the RECS is designed to have a user interface similar to the RECS web page .The tele-emergency system was developed in 2015 and has been applied for emergency teleconsultations. This study analyzed cases between 11 urban hospitals and 75 rural hospitals from May 2015 to December 2018. Cases with missing critical data  were excluded. Enrolled cases were categorized into trauma vs. non-trauma and island vs. non-island to analyze differences in emergency teleconsultation characteristics . The definition of reduction in unnecessary transportation (RUT) case is if the consultation result is a patient’s admission to a rural hospital or discharge and follow-up monitoring from a rural hospital instead of transport to an urban hospital after emergency teleconsultation. This is due to the fact that, in general, rural hospitals make consultation requests for cases that are beyond their treatment or disposition capacity. Without tele-emergency consultations, these patients would be more likely to be transported to urban hospitals rather than being admitted or discharged from rural hospitals. Disease severity is categorized by the Korean Triage and Acuity Scale (KTAS). KTAS was developed based on the Canadian Triage and Acuity Scale (CTAS) and Japan Triage and Acuity Scale (JTAS) with consideration of characteristics of emergency medical service and medical infrastructure. KTAS categorizes a patient’s severity into five levels based on the patient’s subjective or objective signs and symptoms; the most severe patient is categorized as KTAS 1, while the least severe patient is categorized as KTAS 5 ,35,36,37t-test was performed to analyze normally distributed continuous variables (age). Continuous variables were reported as mean and standard deviation. Differences with a p-value < 0.05 were considered to be statistically significant [Data were analyzed statistically using SPSS statics version 24.0 . Univariate analysis for categorized variables  was performed using the chi-square test. The Student’s nificant ,39.This study’s design was reviewed and approved by the institutional review board of Gachon University Gil Hospital (GCIRB2021-445). The requirement for informed consent was waived due to the retrospective nature of the study.Between May 2015 and December 2018, a total of 2985 tele-emergency consultations were performed through the RECS. A total of 381 cases were excluded due to missing data, and a total of 2604 cases were analyzed in the present study .n = 684, 65.9%; p < 0.001), and the patients’ age was higher in non-trauma cases . Tele-emergency consultations for trauma cases most often took place between 18:00 and 23:59 , while non-trauma cases took place between 12:00 and 17:59 . For both trauma and non-trauma cases, the most frequently used consultation method was a video consultation. The proportion of video consultation requests was higher for trauma cases . The reasons for consultation in the trauma cases and non-trauma cases showed significant statistical differences (p < 0.001). Image interpretation was the most common in trauma cases , while transfer requests were the most common in non-trauma cases . The consultation result also showed a significant statistical difference (p < 0.001). Trauma patients were more frequently admitted to rural hospitals or discharged and followed up with at rural hospitals , but non-trauma patients were transferred to urban hospitals more often . In terms of disease severity, the non-severe cases (KATAS 3–5) were statistically higher in trauma cases . The RUT was statistically highly associated with trauma cases   .p = 0.4). The reason for the tele-emergency consultation showed a significant statistical difference (p < 0.001). From the island, transfer requests were highly dominant  while image interpretation was the most common in non-island regions . In both groups, the most common consultation result was transportation, but a statistically higher proportion of transportation was noted for island regions . In terms of disease severity, the non-severe cases (KATAS 3-5) were statistically higher in non-island regions . More RUT was associated with non-island regions  (The characteristics of the comparison between island and non-island tele-emergency consultation cases are described in = 0.001) .This study analyzed the characteristics and effectiveness of the nationwide web- and mobile-based tele-emergency consultation system in South Korea. The present study shows that for trauma cases, rural hospitals mostly requested image interpretation, and patients were more frequently admitted to or discharged from rural hospitals than transportated after tele-emergency consultations. This means tele-emergency consultations performed a significant role in reducing the unnecessary transportation of non-severe trauma patients. Island regions had a higher transportation rate with more severe cases than non-island regions, and the effect of RUT was higher in non-island regions.n = 631, 60.8% vs. n = 670, 42.8%; p < 0.001).Some prior studies have investigated the effect of telemedicine and teleconsultation. Armstrong et al. in their study of the experimental telemedical link between the Aberdeen Royal Hospital in Scotland and the Peterhead Community Hospital showed a 58% decrease in transportation (70 cases out of 116 cases) . Lambrecp < 0.001). For trauma patients especially, visualized information of the injured site is critical. For the visualization of an injury site or the whole body regardless of the patient’s posture, position, or place, real-time video sharing is greatly advantageous. Furthermore, with real-time on-scene sharing, urban hospital doctors can also provide real-time guidance on medical procedures to rural hospital doctors [One of the most significant advantages of mobile devices  is real-time direct on-scene sharing. Some prior studies have shown the effect of video tele-consultations, especially in trauma or injury cases. Roger et al. showed from a study of using telemedicine for real-time video consultations between a trauma center and community hospital that more than 80% of the referring providers felt that telemedicine consultations improved care . Tsai et doctors . This enN = 960, 92.5% vs. N = 1186, 75.9%) could be affected by the convenience of real-time on-scene sharing to visualize the site of injury. In trauma cases, tele-emergency consultation requests for image consultation are significantly more frequent , while for non-trauma cases, transport requests are more frequent . A possible reason for this is that image interpretation from computed tomography or X-rays has critical diagnostic value in trauma cases. However, in non-trauma cases, making a treatment plan for a patient and transferring them to an urban hospital for more appropriate and definitive treatment depending on the disease severity are the most critically important factors. Another characteristic of tele-emergency consultations was the higher transportation rate in island regions than in non-island regions. This could be due to the fact that the only methods of transfer from island regions are marine vessels or air transportation. The limited number of vessels and operation times may have led to more aggressive decisions around patient transportation. As a result, the effect on the RUT was higher in non-island regions than in island regions.The most notable characteristics of tele-emergency consultations in the present study were the significant differences in the reason for consultation, consultation request method, and consultation result between trauma and non-trauma cases, as well as the effect of the reduction in unnecessary transportation in both cases. More video consultation requests in trauma cases (As the most important advantage of mobile and web PACSs, EMRs provide detailed information on a patient’s medical status to doctors and are used to make appropriate clinical decisions about patient management and adequate transportation. They can improve the quality of emergency treatments initially provided to patients and are helpful to prevent unnecessary transportation costs for non-emergency patients. The other advantage of the RECS is the reduced cost of the tele-emergency system set up at urban and rural hospitals. The setup, management, maintenance, and repair of teleconsultation system devices are highly cost-effective projects. Especially in rural hospitals on islands or in mountainous regions, their physical distance complicates system maintenance and management; as a result, system-related feedback between the user and developer cannot be immediate. These drawbacks could be overcome significantly by using a web- and mobile-based RECS.Generally, in trauma cases, after tele-emergency consultations, the non-severe cases were admitted to rural hospitals for treatment, which had a positive effect on the RUT. In contrast, in severe cases, appropriate initial management and quick decisions could be implemented through tele-emergency consultations. Furthermore, urban hospital medical staff members can obtain information about a patient’s medical status in advance, allowing them to prepare for the planned operation or procedure. This environment is expected to bring significant benefits in terms of patient treatment.The present study does have some limitations. Firstly, the RUT could not perfectly reflect the actual reduction in unnecessary transportation. Without the tele-emergency consultation system, the clinical decision in a large portion of these cases would have been to transfer the patient to an urban hospital, but not every decision would have been in favor of urban hospital transportation. For an accurate analysis of the RUT, additional research is needed to investigate changes in physicians’ clinical decisions and rural hospital treatment results before and after tele-emergency consultations. Secondly, our results suggest that tele-emergency consultations can reduce unnecessary transportation and contribute to the efficient use of medical resources. However, an accurate cost-effectiveness analysis was not conducted to determine the actual economic benefit, which is essential for evaluating the RECS. Further studies on the cost-effectiveness of tele-emergency cases are needed. Thirdly, the present study could not analyze the treatment outcomes of the tele-emergency consultation cases. One significant advantage of the RECS is that it provides an early-stage treatment guide, early transportation decisions, and clinical data on emergency patients in advance. Further studies for the evaluation of the long-term medical outcomes of patients for whom an RECS was used are needed.Teleconsultation between rural and urban hospitals is expected to supplement the deficiency in medical services in rural areas. In South Korea, the web- and mobile-based tele-emergency system between rural and urban hospitals greatly reduced unnecessary patient transportation in non-severe trauma and non-island rural area emergency cases. Further research including an analysis of the cost-saving effect of the RUT and the impact of tele-emergency consultations on patients’ clinical outcomes are needed for a reliability assessment of the tele-emergency consultation system.


Escherichia coli and Klebsiella pneumoniae are the two most reported bacteria in causing the bacteremia and nosocomial infections worldwide. In this article, the prevalence of ESBL-producing E. coli and K. pneumoniae in causing blood stream and urinary tract infections in Indonesia were compared to the neighboring countries based on the global antimicrobial resistance surveillance system performed worldwide by World Health Organization (WHO). In this article, the prevalence of ESBL-producing E. coli and K. pneumoniae in Indonesia and its neighboring countries were assayed and compared in order to evaluate the antimicrobial resistances. By comparing the prevalence data to the neighboring countries, some insightful evidence and information was served to support improved health in Indonesia. Some hurdles and strategies in combating the antimicrobial resistances were further discussed. Eventually, an alternate solution to overcome the antimicrobial drug resistance should be well-provided, studied and implemented globally.Antimicrobial resistance is the rising global health issue that should not be ignored. This problem needs to be addressed and professionally handled since it is starting to threaten global health, which eventually could lead to disaster. Extended spectrum beta lactamase (ESBL)-producing bacteria were found threatening lives, since most antibiotics were found to not be effective in treating patients with infections caused by those bacteria. ESBL-producing  ESBL-producing bacteria, such as ESBL-producing Escherichia coli and Klebsiella pneumoniae, are reviewed and listed as the critical priorities for development of new antibiotics based on the data from World Health Organization (WHO) Extended spectrum beta lactamases are produced by specific bacteria called ESBL-producing bacteria which enable those bacterial cells to be more resistant to antibiotics and, therefore, their infections are harder to treat. A previous study performed by Matsumoto 2.E. coli and K. pneumoniae. Meanwhile, the Tricycle Project is focused on monitoring Extended Beta Lactamase-producing E. coli in human, animal (broilers) and the environment. In Indonesia, GLASS activities were begun to be executed in 2018 by collecting resistance data from nine hospitals across several provinces in the country. This data is important to see the pattern of antimicrobial resistances pattern in Indonesia, especially those happened in hospitals. Meanwhile, the Tricycle Project was carried out in 2017–2018 by involving two hospitals which were also GLASS sentinel sites. Therefore, a correlation between the two activities was predicted. In this article, the data of ESBL-producing E. coli and K. pneumoniae in Indonesia compared to neighboring countries based on GLASS data in 2018 obtained from WHO database was presented The World Health Organization (WHO) has responded to several activities, including the Global antimicrobial resistance surveillance system (GLASS) and the Tricycle Project 3.E. coli and K. pneumoniae are two infectious bacteria that have become a serious concern for nosocomial infections worldwide, especially Indonesia. E. coli is a common Gram-negative bacterium that belongs to the normal human microbiome. However, E. coli itself was also reported to be responsible for blood stream infections (BSI), which could be leading to community and hospital acquired BSI K. pneumoniae was well-known for being responsible pathogen for pneumonia, septicemia and urinary tract infections (UTI). In a previous reported study of ESBL-producing K. pneumoniae that were isolated from patients with nosocomial infections, showed high rates of resistances against ciprofloxacin (86.2%), tetracycline (80.9%) and nalidixic acid (78.7%) ESBL-producing E. coli data on GLASS activities are similar to previous published Tricycle Project data E. coli and K. pneumoniae to third generation cephalosporin antibiotics , similar to that possessed by Myanmar and Laos -IId-like, strA, strB, aac(3)-IIa-like, strA-like, strB and aac(6′)Ib-cr, responsible for ESBL production and multi drug resistances were figured out The coliform-appearing ESBL-producing Enterobacteriaceae isolated in an urban West African rat population in a study performed by Schaufler 5.et al. Several approaches, such as increasing the global collaboration between governments non-government organizations (NGOs), professional groups and international agencies have been addressed as the approaches to combat antimicrobial resistance, in addition to rational drug use, infection control and prevention, antimicrobial surveillance, ban on OTC antibiotics, giving proper education and motivation, increasing and elaborating the research and development of drug and vaccine, new AMR programs, global policies formulation and building a global AMR committee


N = 6732 humans) and 182 preclinical  studies. A general impairment of learning, memory and extinction processes was observed in PTSD patients, regardless of information valence. Impaired neutral learning/memory and fear extinction were also present in animal models of PTSD. Yet, PTSD models enhanced fear/trauma memory in preclinical studies and PTSD impaired emotional memory in patients. Clinical data on fear/trauma memory was limited. Mnemonic phase and valence explained most variation in rodents but not humans. Impaired neutral learning/memory and fear extinction show stable cross-species PTSD phenotypes. These could be targeted for novel PTSD treatments, using information gained from neurobiological animal studies. We argue that apparent cross-species discrepancies in emotional/fearful memory deserve further in-depth study; until then, animal models targeting this phenotype should be applied with utmost care.Current evidence-based treatments for post-traumatic stress disorder (PTSD) are efficacious in only part of PTSD patients. Therefore, novel neurobiologically informed approaches are urgently needed. Clinical and translational neuroscience point to altered learning and memory processes as key in (models of) PTSD psychopathology. We extended this notion by clarifying at a meta-level (i) the role of information valence, i.e. neutral versus emotional/fearful, and (ii) comparability, as far as applicable, between clinical and preclinical phenotypes. We hypothesized that cross-species, neutral versus emotional/fearful information processing is, respectively, impaired and enhanced in PTSD. This preregistered meta-analysis involved a literature search on PTSD+Learning/Memory+Behavior, performed in PubMed. First, the effect of information valence was estimated with a random-effects meta-regression. The sources of variation were explored with a random forest-based analysis. The analyses included 92 clinical ( After a severe traumatic experience, some individuals may develop posttraumatic stress disorder (PTSD) . PTSD syClinical and translational neuroscience have generated models of PTSD psychopathology that highlight abnormalities in the neurocircuitries underlying fear learning, threat detection, emotion regulation, and context processing (in fear and reward) –14, yet Together the evidence above illustrates that (1) learning and memory processes play a central role in PTSD pathology, and (2) abnormalities in the underlying neurobiological systems are likely to affect the processing of both emotional/fearful and neutral information, which in turn can influence treatment efficacy. To date, though, there is no comprehensive systematic literature overview available that evaluates PTSD patients’ abilities to learn and memorize neutral and emotionally valenced information together. To fill this gap, we performed a systematic review and meta-analysis to provide a comprehensive overview of current knowledge on learning and memory in PTSD, assessed with behavioral tasks including neutral, emotional, and fearful information (plus fear extinction). Although PTSD is a uniquely human disorder, animal models can offer valuable insights into PTSD’s neurobiology and foster drug-development when their phenotype aligns -at least partly- with specific aspects of clinical presentation –33.To provide a comprehensive overview of the learning and memory phenotype in current animal models of PTSD, preclinical studies were evaluated in addition to clinical studies. Our primary aim was thus to evaluate the cross-valence mnemonic performance of (i) PTSD patients and (ii) animals in PTSD models, compared to their appropriate healthy control group, keeping in mind the limitations of such a cross-species approach. As demonstrated by PTSD psychopathology models –20, neurImportantly, PTSD’s heterogeneous nature leads to a diverse patient group , 36, andhttps://osf.io/wn34s).This preregistered project (PROSPERO CRD42017062309)  is perfohttps://osf.io/8ypm5/). A comprehensive literature search on PTSD + Learning and MemoryMaterials, data, and R-code used for literature search, screening, data extraction, and meta-analysis are available via OSF   see App in the cα = 0.05 in R version 4.0.3  = 0.081 [0.106]). The ranking of the moderators is shown in Fig. 2) do not suggest strong moderation. Indeed, the follow-up PD plots suggest that performance is generally impaired (Hedge’s G ~ −0.5) across all levels of the evaluated moderators . This is a considerable amount, and the variable ranking shown in Fig. For the preclinical data, 53.4% of the variance in effect sizes was explained by the variables evaluated with MetaForest  information in PTSD patients and animal models of PTSD. The results confirmed the hypothesis that neutral learning/memory and fear extinction are cross-species impaired in PTSD, but the expected stronger fear memory in PTSD was only observed in preclinical studies . This emphasizes that preclinical researchers should carefully evaluate their phenotype of interest cross-species before selecting an animal model to make inferences about the neurobiology underlying clinical aspects of PTSD .Of note, clinical and preclinical studies differed in many characteristics. Clinical studies mostly investigated older patients of mixed gender, while preclinical studies typically included younger, male animals which -in terms of genetic background and housing conditions – were quite homogeneous. Stronger effect sizes were observed in preclinical studies (likely due to their controlled nature) and overall reporting on potential risks of bias was better in clinical studies. Importantly, animals exposed to trauma were typically considered to represent ‘the PTSD group’ in most preclinical studies. This is an inaccurate conceptualization of PTSD, as clinical studies showed that only a minority of trauma-exposed individuals actually develop PTSD, which was confirmed in those animals studies that addressed the issue (reviewed in ref. ). UnfortPartly as expected, learning, memory, and extinction were impaired in PTSD patients. This impairment is strong for both neutral as well as emotionally valenced material. No strong moderators of these effects were identified, suggesting a general impairment of learning and memory processes in PTSD patients. This contrasts, for example, with earlier reports on the influence of sex on fear conditioning , or on HIn line with earlier seminal research (reviewed in refs. –85), ourReduced ability to learn and memorize neutral information was another strong phenotype in both PTSD patients and animal models. This phenotype should not be overlooked in PTSD research  and cliContrary to fear extinction and neutral memory formation, our meta-analysis suggests that PTSD might have opposing effects on emotional  and fearful/trauma memory  in clinical versus preclinical studies respectively, although the differences in these two lines of research are extensive and ask for very careful comparison of the results. One neurobiological explanation may be linked to the stress system. Thus, in humans emotional memory tasks are unlikely to trigger activation of the HPA-axis (e.g. ref. ), while The large cross-species dataset (274 studies), and integrated hypothesis-driven meta-regression with state-of-the-art heterogeneity exploration via random-forest and tree-based models are strengths of this meta-analysis. To improve cross-species comparability, only behavioral measures of learning and memory  were included, which might limit the generalizability of our findings to, for example, neuroimaging or self-report measures.All in all, this meta-analysis shows that both impaired neutral learning/memory and fear extinction are two strong clinical phenotypes of PTSD, that can be accurately modeled in preclinical studies. Novel PTSD treatments could target these phenotypes and benefit from animal models to unravel the underlying neurobiology and foster drug-development. In addition, future research should elaborate on the origin of potential differences between emotional and fear/trauma memory in PTSD across species. Until this issue is resolved, we do not recommend to use animal models for drug-development that targets emotional/fearful memory in PTSD.PRISMA checklistSupplemental Information (Appendix)Reference list meta-analyses


Background: Upper limb apraxia (ULA) is a neurological syndrome characterized by the inability to perform purposeful movements. ULA could impact individuals’ perceptions, including perceived self-efficacy. The aim of this study is to investigate whether ULA is related to general self-efficacy and self-efficacy for managing symptoms in post-stroke patients. Methods: A cross-sectional study was conducted involving 82 post-stroke patients. Regression analyses were implemented using a stepwise model including seven dimensions of ULA: imitation , pantomime , and dimension of apraxic performance in activities of daily living. These dimensions were independent variables, while general self-efficacy and symptom management self-efficacy dimensions were dependent variables. Results: The findings revealed that intransitive imitation accounted for 14% of the variance in general self-efficacy and 10% of self-efficacy for managing emotional symptoms. Transitive imitation explained 10% of the variance in self-efficacy for managing global symptoms and 5% for social–home integration symptoms. The combination of intransitive imitation, non-symbolic pantomime, and alterations in activities of daily living performance associated with ULA explained 24% of the variance in cognitive self-efficacy. Conclusions: Hence, ULA dimensions seem to be related to the levels of general perceived self-efficacy and self-efficacy for managing symptoms among post-stroke patients. Upper limb apraxia (ULA) is a neurological syndrome that has a substantial impact on the functional interaction between individuals and their environment. The main clinical symptom of ULA is the incapacity to perform deliberated movements upon a request from a person or the context, especially in hands. ULA is usually considered a heterogeneous syndrome historically defined by the exclusion of several health parameters, ordered by frequency in the literature: (i) motor and sensory impairments, (ii) comprehension deficits, (iii) weakness, (iv) coordination impairments, (v) intellectual deterioration, (vi) uncooperativeness, (vii) lack in motivation, (viii) cognitive deficits (memory and attention), (ix) movement alteration , (x) disorder of tone or posture, and (xi) object recognition difficulties ,2,3. ULAThe primary clinical manifestation of ULA is the inability to execute deliberated, voluntary, and purposeful movements in response to a request from an individual or the environment. These movements may be classified based on the nature of the action performed. Transitive movements involve manipulating objects, while intransitive movements are performed without using objects. Symbolic movements are those that have social or cultural significance, whereas non-symbolic movements do not have any such significance. The main sensory pathways through which information required to configure a movement is typically received include the auditory and visual modalities . On the The classification of apraxia has historically been divided into two main groups, ideomotor and ideational apraxia; however, contemporary research understands this syndrome in a broader and more complex manner. A deeper comprehension of ULA requires an analysis that integrates the assessment of apraxic errors with a diverse range of gestures that represent a wide spectrum of upper limb movements . These gGeneral self-efficacy is commonly defined as the comprehensive belief in one’s capability to effectively perform actions aimed at managing personal and everyday life goals. Bandura characterized self-efficacy by four primary sources: direct mastery experiences, vicarious experiences, verbal persuasion, and physiological state . These pDomain-specific self-efficacy for managing symptoms is the ability to perform actions to achieve specific goals related to different types of symptoms. These goals could be recognizing and adapting to the symptoms, evaluating risk situations, and preventing health complications . Domain-The presence of ULA often leads to difficulties in performing activities of daily living, which can result in perceptions of dependence and limitation ,30. FurtA cross-sectional, observational, and descriptive study was conducted. The participants were post-stroke patients recruited from the Andalusia public health system.The inclusion criteria for the participants were (i) having mild to moderate sequelae assessed using the National Institutes of Health Stroke Scale (NIHSS) , (ii) bet test family and a linear multiple regression fixed model single regression coefficient including seven predictors, one-tailed. Considering a moderate effect size of f2 = 0.15 [The sample size for this study was determined using G*power. A priori computed required sample size estimation was conducted using a 2 = 0.15 ,38, a deA total of 189 post-stroke patients met the criteria for suitability and agreed to participate in the study. From this group, 82 participants were selected, with 41 individuals having ULA and 41 without ULA. ULA was evaluated using the Apraxia Screen of TULIA (AST) test, where a score of <9 points indicates the presence of apraxia . A matchPatients were gathered from randomly selected primary care centres during the period of April 2022 and June 2023. Prior to their appointments, they were provided with detailed information about the study. Individuals who expressed interest in participating were given an informed consent form and a participant information sheet. Afterwards, the evaluation of ULA and self-efficacy was implemented during a one-and-a-half-hour session. The evaluation system was applied by a researcher who has specific training in evaluations of post-stroke patients and upper limb apraxia and more than ten years of clinical expertise in upper limb apraxia. The data collection and evaluation process was implemented in the following order: first, sociodemographic and clinical information was collected; second, the general self-efficacy and the self-efficacy in symptom management scales were administered; and finally, the TULIA test and the ADL observation scale were implemented. The Ethics Committee for Biomedical Research CEI-Granada in the Province of Granada  approved this study with reference: 1503-N-21. The research study adhered to the ethical guidelines outlined in the Declaration of Helsinki throughout the entire research process, including data collection.Researchers gathered information on socio-demographic data , self-reported lifestyle behaviours , clinical information , and stroke characteristics .The general self-efficacy scale was utilized to assess general self-efficacy in the study. This scale consists of 10 items that measure an individual’s self-perceived ability to cope with stressful situations. Each item is rated on a 10-point Likert scale, ranging from 0 (indicating ‘completely disagree’) to 10 (indicating ‘completely agree’). Higher scores on the scale indicate higher levels of self-efficacy. The psychometric properties of the scale in the Spanish population demonstrate significant internal consistency, with alpha coefficients ranging from 0.79 to 0.93, indicating a reliable measure of self-efficacy. Additionally, the scale exhibits strong correlation with other measures of self-efficacy, with a correlation coefficient of 0.88 . The stuSelf-efficacy for managing symptoms was evaluated using the self-efficacy in symptom management scale after the traumatic brain injury. This is a specific questionnaire that evaluates self-efficacy after brain damage. It contains 13 items divided into three dimensions: perception of self-efficacy for managing social and community situations , management of physical or cognitive symptoms (cognitive self-efficacy), and management of emotional symptoms . The internal consistency of the scale for the Spanish population showed notable internal consistency. Social–home integration, cognitive and emotional dimensions, and the total score of the scale showed a Cronbach’s alpha coefficient of 0.66, 0.93, 0.89, and 0.89, respectively .The Comprehensive Assessment of Gesture Production (TULIA) test was used to evaluate the imitation and pantomime dimensions. The TULIA comprises 48 items that are categorized into six differentiated dimensions (sub-constructs of apraxia): non-symbolic imitation (meaningless); intransitive imitation (communicative); transitive imitation (tool related); non-symbolic pantomime; intransitive pantomime; and transitive pantomime. These items assess various kinematic features, including proximal and distal movements, as well as simple and repetitive actions. Each item is scored on a scale ranging from 0 to 5, with a score of 5 indicating normal movement. The total score ranges from 0 to 240, with lower scores indicating a greater presence of ULA. For stroke patients, the authors established a cut-off score of 194 points to identify the presence of ULA. The TULIA test has shown adequate psychometric properties, including internal consistency , and high intraclass correlation (0.96 for imitation and 0.99 for pantomime) .The ADL observation scale is a validated unidimensional tool specifically designed to assess the ADL performance associated with ULA. The evaluation is based on the observation of the performance of four daily activities, three of which are previously established, and the other is chosen by the evaluator. The scoring method consists of four aspects: independence, initiation, execution, and control. Higher scores indicate greater dependence on these activities, reflecting the impact of ULA. The individual scores for each activity can be summed to obtain a total score, providing a comprehensive measure of ULA-related disability. The ADL observation scale demonstrates strong internal consistency, with a Loevinger’s H-coefficient of 0.58 and a rho-value of 0.94, indicating its reliability in measuring ULA. Moreover, the tool exhibits high inter-observer reliability, as evidenced by strong agreement between observers, with an intra-class correlation coefficient of 0.98, particularly for the total score of the assessment .t-test and Chi-Square test were run for continuous and categorical variables, respectively. To identify if ULA dimensions are associated with self-efficacy dimensions, five separate multiple linear regression analyses were performed with the total sample of post-stroke patients (n = 82). The stepwise regression approach was used to select the significant predictors for each self-efficacy dimension, considering the seven ULA dimensions as potential predictors. Specifically, dependent variables were general self-efficacy and self-efficacy for managing symptoms dimensions: social–home self-efficacy, cognitive self-efficacy, emotional self-efficacy, and the total score of self-efficacy for managing symptoms. The independent variables comprised the seven dimensions of ULA, that is, the six dimensions of the TULIA test , and the total score of the ADL observation scale. Before conducting the regression analyses, the normality of the variable distributions and the presence of multicollinearity were assessed. The variance inflation factor (VIF) was utilized as an indicator of collinearity, and normality was evaluated using appropriate statistical tests. Statistical significance was determined using a p-value threshold of less than 0.05.The collected data were analysed using SPSS version 26.0. To gain insights into the dataset, descriptive statistics were employed to summarize the key variables, including means, standard deviations, frequencies, percentages, ranges, minimums and maximums, and percentiles), To perform a between-group comparison, the independent The descriptive statistics for the seven dimensions of ULA are shown in p < 0.001) and 10% (p = 0.003) of its variance, respectively. Transitive imitation explains 10% (p < 0.001) and 5.2% (p = 0.035) of the variance in self-efficacy for managing symptoms and social–home integration. Intransitive imitation, the total score of the ADL observation scale, and non-symbolic pantomime explained 24%  of the cognitive self-efficacy variance. These results are shown in Regarding self-efficacy dimensions, results after linear regression analyses have shown that intransitive imitation dimension was significantly associated with general and emotional self-efficacy, explaining 14%  incorporating self-efficacy assessment in individuals with stroke and apraxia; (ii) implementing strategies to improve stroke symptom management abilities; and (iii) guiding healthcare professionals in designing personalized management of self-efficacy perception in this population. On the other hand, from the research area, the practical application may involve (i) a better understanding of the relationship between praxic function and self-efficacy; (ii) the opening of future research in the early identification of the perceptual sphere regarding the patient’s interaction with the environment through movements after a stroke; and (iii) the importance of including ULA as a relevant construct in the design of studies involving patients with low levels of self-efficacy.Some limitations may be identified in this study: first, the sample was limited to patients from a single Spanish province, which could reduce the generalizability of the findings to a broader population; second, data about the professional work of the study participants were not collected, which could have provided valuable insights into characterizing the sample; third, the study was based on a cross-sectional design, which restricted the ability to observe changes over time and identify longitudinal patterns in the relationship between ULA and self-efficacy.The findings of this study identified significant associations between self-efficacy dimensions and the ULA dimensions. Specifically, general self-efficacy and self-efficacy for emotional symptoms were positively associated with apraxic errors in objectless gesture imitation. Self-efficacy for managing global and social interaction symptoms was influenced by the alteration of transitive gesture imitation. Additionally, self-efficacy for cognitive symptoms was related to apraxic error performance in activities of daily living performance, intransitive imitation, and meaningless pantomime. These results highlight the importance of considering the dimensions of apraxia when approaching perceived self-efficacy in post-stroke patients.