Neuromyelitis Optica (NMO) is a serious condition associated with inflammation. Early diagnosis and detection are critical for early intervention. In this systematic review, we investigate the role of the neutrophil to lymphocyte ratio (NLR) as an important biomarker for NMO.Ten studies were selected that were sufficiently high quality and then checked for quality. The studies were organized by English language and selective inclusion criteria.NLR was significantly increased in NMO patients compared to controls. The ratio was specifically proportional to severity of disease. More severe disease had a higher ratio.NLR offers a reliable and affordable method for early detection of disease severity. This can help guide appropriate treatment selection and monitor treatment response. Neuromyelitis optica spectrum disorder (NMOSD) is a neurodegenerative disease and defined as an inflammatory autoimmune disease of the central nervous system (CNS) which clinically presents as acute optic neuritis (ON), transverse myelitis (TM), and brain and/or spinal cord syndromes and follows a relapsing/remitting course -3. BasedNLR is a widely used reliable biomarker to assess the prognosis of many diseases, including systemic lupus erythematosus , Behçet’In addition, a few researchers have reported the association between NLR and NMOSD. However, all the research up to now has been descriptive in nature. Also, literature has emerged that offers contradictory findings about the relationship. In addition, most studies in this context have only been carried out in a small number of areas and a limited number of patients. These indicate a need for a systematic review which consolidates the available data to help guide further clinical management with the predictive capabilities of the NLR. The aim of this study is to systematically review the evidence on the association between NLR and NMOSD diagnosis, prognosis, and severity. This significantly aids in improving treatment. To the best of our knowledge, our manuscript is the first systematic review in this context.th of November 2021 using the following terms: (“neutrophil to lymphocyte ratio” NLR) AND (NMOSD OR “neuromyelitis optica spectrum disorder”)  criteria were used to report this systematic review. We conducted a systematic search in three main databases, including Scopus, PubMed, and Web of Science. This was done on the 28sorder”) . Manuall(a) Population: Patients with NMOSD(b) Intervention: NLR(c) Control: Healthy control patients(d) Outcomes. The diagnostic and prognostic performance of NLR OR association of NLR with other factors(e) Study design: cross-sectional, case-control, and cohort studiesWhen studies met all the above requirements, they were considered eligible. There were no restrictions on article language or publishing date. Articles were not accepted if they fit into any of the following categories: (1) overlapping or duplicating data; (2) case reports, conference proceedings, reviews, and letters to the editor. When numerous publications or data analyses were presumably from the same data source, and no confirmation on potentially duplicate data was available, the study with the most patients was kept, and other relevant studies were eliminated. Corresponding authors were contacted to explain incomplete or ambiguous data, but no further data was obtained.The following data was extracted:(1) Name of the first author, (2) year of publication, (3) country of data source, (4) study design (retrospective or prospective), (5) sample size, (6) male to female ratio, and (7) key results.The Newcastle– Ottawa Scale (NOS), comprising three sections of selection, comparability, and outcome of interest, was used to assess the quality of the included studies. NOS values varied from 0 to 9.Lin et al.  initiateBenetou et al.  initiateQingli et al.  retrospeIn another article, Xie et al.  reportedTong et al.  analyzedPeternell et al.  conducteContentti et al. [i et al.  studied It has been established that the complement C3 and C4 levels in NMOSD patients were lower compared to those in healthy controls . So, PanZhou et al.  publisheChen et al.  retrospeThe main result of the current systematic review study was that NLR increased among patients with NMOSD compared to healthy controls and those with other types of neuro-autoimmune disorders, including MS and MOGAD. This is important because these diseases are often included in the differential diagnosis list of NMOSD. The results showed that NLR during steroid treatment increased artificially. In addition, NLR levels in the attack stage were higher than remission stage. NLR was positively associated with the EDSS score, a scoring system for disability in NMOSD, and could predict the relapse of NMOSD.A significant part of many chronic diseases is played by inflammation and immunity. The neutrophil-lymphocyte ratio (NLR), measured as a simple ratio of neutrophil and lymphocyte counts in peripheral blood, is a biomarker that indicates the balance of two elements of the immune system: adaptive immunity and acute and chronic inflammation (as demonstrated by the neutrophil count). NLR has been widely studied and shown to relate to mortality and predict course of illness in patients suffering from a range of medical disorders such as cerebral hemorrhage, infectious diseases, sepsis, ischemic stroke, and major cardiac events. Besides that, higher NLR has been linked to a poor prognosis in cancer patients. These negative associations could be due to the roles of poor immune function and severe inflammation in the progression of these illnesses. Furthermore, it has been suggested that increased NLR is an independent and complementary indicator of the degree of neurological dysfunction brought on by multiple sclerosis. To inform future clinical care using the NLR’s predictive capacity, we compiled the information that is currently available on the function of the NLR in predicting NMOSD.NMOSD is an uncommon and disabling condition marked by inflammatory episodes affecting the spinal cord and optic nerves . BecauseInvestigating the roles of neutrophils and lymphocytes is essential to attain a comprehensive explanation for NLR as a biomarker in NMOSD. Although neutrophils have long been seen in Central nervous system (CNS) lesions and Cerebrospinal fluid (CSF) of NMOSD cases, their involvement in NMOSD pathophysiology has not yet been known entirely -39. NeutNeutrophils, macrophages, and eosinophils are the most recruited inflammatory cells in the NMOSD lesions, as well as a few T lymphocytes ,43. ThesLevels of Interleukin (IL)-17 and IL-8 are increased in Cerebrospinal fluid (CSF) of NMO patients, which could answer why there are more neutrophils in NMO . intrathIn vitro investigations have shown anti-AQP4 Ab bound astrocytes to cause complement-dependent granulocyte migration through the BBB [ the BBB . The deg the BBB ,49. Piat the BBB  investigB cells and T cells have been shown to play significant roles in the development of NMOSD in numerous investigations. Anti-AQP4 antibodies are often generated by CD19, CD38, and CD27 phenotypic B cell subsets . In addiThe contribution of B lymphocytes and plasma cells in NMOSD can be perceived by the pathogenic effect of AQP4-ab ,56. LeveHowever, the role of B cells in the pathophysiology of NMOSD may go beyond the synthesis of AQP4-ab. B cells may also serve as antigen-presenting cells to form follicular effector T cells that play a role in isotype switching and differentiation ,61, lead+ T cells are involved in developing this adaptive humoral response [In NMO patients’ serum, AQP4-ab are IgG1, a subtype of mature IgG that needs T cell assistance, implying that AQP4-specific CD4response . T cellsresponse . T cellsresponse ,65. In rresponse .+ regulatory T cells [AQP4 antigenic activation polarizes the immune reaction toward a Th17 repertoire and the release of Th17-associated cytokines, including IL-21 and IL-6 . Th17 ce T cells . These fTherefore, in the NMOSD immunological response, neutrophils and lymphocytes play critical roles. As the forerunners of the immune response, neutrophils secrete a considerable number of inflammatory mediators. Activated lymphocytes, on the other hand, release superoxide radicals and proteases. All these variables contribute to tissue damage ,33. NLR Our systematic review has two significant limitations. First, most of the included research was retrospective. Future prospective research should be conducted to confirm these results. Second, due to high heterogeneity and inconsistent findings in the literature, as well as the absence of a sufficient number of studies to be acceptable for a meta-analysis, we were unable to conduct a meta-analysis. Because there were some controversies among the results of included studies, more research on this topic needs to be undertaken before the association between NLR and NMOSD is more clearly understood.The results of our study support an association between NLR values and the development of NMOSD. NLR represents a unique inflammatory marker whose elevation in NMOSD implicates immune system imbalance in the pathogenesis of the disease. Further, our findings support NLR to be a promising biomarker that can be readily integrated into clinical settings to aid in predicting and preventing NMOSD-induced disability. Ultimately, with the development of new biomarkers and therapeutic modalities, we can better prevent and treat NMOSD to decrease long-term morbidity and mortality.


Achalasia, a neurodegenerative disease caused by the progressive destruction of ganglion cells in the myenteric plexus, is accompanied by incomplete relaxation of the lower esophageal sphincter. Laparoscopic Heller's myotomy (LHM) coupled with fundoplication has been the gold standard procedure for achalasia. Peroral esophageal myotomy (POEM) has recently gained popularity as it is minimally invasive, has fewer adverse events, and has excellent short-term outcomes. So, we aimed to compare the clinical efficacy, safety, and postoperative outcomes between LHM and POEM.We did a systematic review by following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines for 2020 and exploring research databases such as PUBMED and PMC Central, Google Scholar, and Research Gate. After appropriate screenings, articles relevant to the review were scrutinized based on the eligibility criteria. Quality assessment tools such as the Newcastle-Ottawa Scale (NOS) and the assessment of multiple systematic reviews (AMSTAR) were used to finalize the articles. A total of 11 articles  were included in the review after a quality check. The study included 2127 patients, classified into 981 for POEM and 1146 for LHM, who had undergone treatment for achalasia. Most of the studies had a follow-up of ≤ two years. Postoperative reflux and the development of esophagitis remain certain with POEM and need to be followed up with more studies with longer follow-ups. However, POEM still stands as a better choice compared to LHM in terms of efficacy and safety.Comparing efficacy, POEM had similar results to LHM in terms of Eckardt scores. However, abnormal DeMeester scores were found in POEM. Adverse events were significantly higher in LHM when compared to POEM in terms of safety. Peroral esophageal myotomy also stood out as having a shorter procedure time, a shorter hospital stay, and lesser odds of being a clinical failure. As for postoperative outcomes, despite treatment with proton pump inhibitors, LHM was more effective in preventing the development of esophagitis compared to POEM due to partial fundoplication. Achalasia is an uncommon and rare esophageal motility disorder resulting from the loss of inhibitory neurons from progressive destruction and degeneration of the myenteric plexus, thereby leading to impaired relaxation of the lower esophageal sphincter (LES) and esophageal aperistalsis . The incHeller's myotomy, first described in 1913 by German surgeon Ernst Heller, was modified in 1991 with the advent of the laparoscopic technique and became the gold standard with better long-term outcomes and fewer retreatments compared to PD . RecentlTo date, very few studies have demonstrated the safety and clinical efficacy by comparing the two procedures and found the results to be similar. Therefore, this systematic review aimed to compare and analyze clinical efficacy, safety, and postoperative outcomes with adequate follow-up.MethodsSearch StrategyThis systematic review was planned and performed using the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines (PRISMA) 2020 to report the results . A comprFor MEDLINE, PubMed, and PMC, Medical Subject Heading (MeSH) was used to screen appropriate keywords pertaining to the topic and systematically identify relevant full-text articles -13. The Inclusion and Exclusion CriteriaObservational studies, systematic reviews, and randomized clinical trials (RCT) published in English in the past 10 years were included. Exclusion criteria included articles pertaining to the pediatric population, grey literature, editorials, and animal studies. The full inclusion and exclusion criteria are listed in Table Qualitative AnalysisA critical evaluation of articles was done for quality check and included 11 articles for final review. Quality assessment tools such as the Newcastle-Ottawa scale (NOS) for observational studies and assessment of multiple systematic reviews (AMSTAR) for systematic reviews and meta-analyses were used. Studies were assessed and graded based on the above quality assessment tools and only those that fulfilled as high quality were included in the final study. A comprehensive table depicting the quality converted according to standards  is given below in Table The randomized clinical trials ,21 were Data ExtractionTwo investigators independently reviewed and extracted the data for all eligible studies related to the topic and screened them using the inclusion and exclusion criteria. Studies were assessed based on Eckardt scores, esophageal function for efficacy, adverse events and complications for safety, and the development of esophagitis in postoperative outcomes. All disagreements were resolved between the reviewers by reaching a consensus.ResultsUsing the appropriate MeSH strategy, 936 articles were found in PMC and PubMed. These included systematic reviews, RCTs, and observational studies. A total of 774 articles remained after filtering them using the basic exclusion criteria . Around 527 articles were left after removing the duplicates. Articles were then carefully screened using abstracts, full-text papers, and detailed inclusion and exclusion criteria  metrics, and timed barium esophagogram (TBE) in the efficacy spectrum. Studies that compared the postoperative reflux between the two techniques found that POEM had a greater propensity for the development of GERD using the esophageal pH study findings, as POEM was not usually coupled with fundoplication compared to LHM . StatistDiscussionBy comparing the treatment of achalasia with LHM and partial fundoplication as the gold standard and the use of POEM, studies have shown us the benefits of excellent short-term clinical outcomes with the latter . HoweverIn a study done by Sanaka et al., the results showed that the rate of esophageal exposure was higher in POEM compared to LHM  and that GERD symptoms had no statistical difference between POEM and LHM with fundoplication . An RCT Assessment of EfficacyAll of the included studies assessed the efficacy spectrum between POEM and LHM in terms of Eckardt scores, dysphagia scores, esophageal function post-treatment, TBE, and HREM in varying combinations. Each of the 11 studies stood out in terms of demographics such as population, study sample, study design, and eligibility criteria.A prospective cohort study conducted by Kahaleh et al. over five years in Latin America included 113 patients, divided into 69 for POEM and 64 for LHM. A total of 35 patients had Chagas disease, out of which 17 were in POEM and 18 in LHM. Eckardt score and HREM pre- and post-POEM have been evaluated at three-, nine-, and 12-month follow-ups. The preprocedural assessment for Eckardt's score was 8.72 vs. 7.4 in the POEM vs. LHM groups, respectively (p < 0.001). Post-procedure, it was reduced to 1.84 vs. 3.6 in POEM vs. LHM (p < 0.001), respectively, at a follow-up of 16 months vs. 22 months in POEM vs. LHM (p = 0.0001). The initial therapy success rate was relatively high, at 86% in POEM vs. 60% in LHM. The preprocedural LES pressure was similar in both groups and was reduced to 14.3 mmHg in POEM and 19.8 mmHg in the LHM group post-procedure (p = 0.00231). This study concluded that POEM had a higher rate of initial success and was beneficial in a specific population due to the longer myotomy that it offers .Kumbhari et al. conducted a retrospective study for patients with achalasia type III who underwent POEM (n = 49) across the US, Asia, and Europe, which was compared to an LHM (n = 26) done at a single tertiary institution in the US, respectively. Patients were classified according to the Chicago classification criteria. The preprocedural Eckardt stage in LHM compared to POEM had a higher mean baseline . Eckardt's symptom stage reduced to < 1 was statistically significant with POEM vs. LHM  for a follow-up of 8.6 vs. 21.5 months, respectively. Since the study was performed in different geographic locations under diverse expertise, a larger proportion of the LHM group had a higher baseline Eckardt stage, and the follow-up in the POEM group was comparatively shorter, which could have led to a favorable bias toward POEM .A retrospective study by Sanaka et al. in 2016 compared patients between LHM (n = 142), POEM (n = 36), and PD (n = 22) in terms of esophageal function based on TBE and HREM findings pre- and post-treatment at two months. Most of the patients who underwent POEM and PD had undergone prior treatments compared to the LHM group. The results showed no significant difference in the pre-treatment TBE and HREM parameters in all treatment groups (p > 0.05). The TBE's parameters included barium column height, width, and volume remaining measured at both one- and five-minute intervals. Actual barium height at two-month follow-up decreased by 50% in LHM and 47% in POEM (p = not significant). The HREM was measured on the scale of basal LES pressure and integrated relaxation pressure (IRP), which was reduced to less than 10 mmHg in 72% of LHM and 73% of POEM patients (p =not significant). The study had its limitations in age, BMI, and prior treatments in the POEM group, along with the statistical difference .A cohort study done in a retrospective fashion by Pascale et al. between 2012 and 2015 had 74 patients divided into 32 for POEM and 42 for LHM. Preoperative assessment included an Eckardt score > 3, barium swallow, HREM findings, and esophagogastroduodenoscopy (EGD), which confirmed the diagnosis. The two groups were matched for age, sex, and previous treatment for achalasia. The median preoperative Eckardt score was six for both groups . A follow-up at 23 and 26 months for POEM and LHM, respectively, showed the Eckardt score was reduced to one in both groups (p = 0.001). This study tells us that there is no significant difference between the groups. However, the study had no predefined criteria for selecting a procedure and included patients who had had prior interventions .In a study done by Schneider et al., patients were matched according to the eligibility criteria, which included Eckardt score, dysphagia severity score, QoL in reflux and dyspepsia (QOLRAD), and GERD-health-related quality of life (GERD-HRQL) questionnaire. A total of 25 patients in the POEM and 25 in the LHM group were matched according to the study's criteria. The preoperative mean Eckardt score was 6.6 (+/- 2.3) in both groups. Eckardt score < 3 was 91% and 84% in the POEM and LHM groups, respectively (p = 0.444). The four metrics mentioned above also improved in both groups at a median follow-up of 158 weeks for LHM and 36 weeks for POEM .An RCT conducted by Werner et al. from 2012 to 2015 had a total of 221 patients randomized into LHM with fundoplication (n = 109) and POEM (n = 112). Clinical success was observed in 83% of POEM patients and 82% of LHM patients at two years of follow-up. The esophageal function was assessed objectively by measurement of IRP using HREM, which showed no significant difference . The gastrointestinal QoL metrics between baseline and 24 months showed no difference as well . However, this study had a serious limitation since less than 50% of eligible patients participated in the study [A meta-analysis done by Marano et al. included papers between 2005 and 2015 involving 486 patients (n = 196 for POEM and n = 290 for LHM), in which five studies reported no significant difference between POEM and LHM in terms of Eckardt score reduction (p < 0.001). Since significant heterogeneity was present among the studies, random effect analysis was done to reduce the heterogeneity. One of the limitations of the study was that the follow-up was not more than a year, was non-randomized, and included patients with previous esophageal interventions . A compaAssessment of SafetySanaka et al. in 2019 compared abnormal esophageal acid exposure and DeMeester score by performing a 24-hour pH study two months post-treatment between 31 POEM patients and 88 LHM patients. Patients were matched according to age, gender, race, BMI, and duration of symptoms. The results of this study showed that abnormal esophageal acid exposure was greater in POEM vs. LHM patients  with an abnormal DeMeester score of 54.8% vs. 17.4%; p = 0.005). This subset of the POEM group had a greater number of prior achalasia interventions compared to the LHM group . There was no significant difference between POEM and LHM in terms of GERD symptoms  [A prospective cohort study done by Hungness et al. in 2012 compared the perioperative outcomes between LHM and POEM in a non-randomized fashion. It included 73 patients  who were matched, including the absence of prior treatments. The results showed that operative times were shorter for POEM  and the estimated blood loss was less compared to LHM . Adverse events and hospital stays were similar . The safIn the study done by Kahaleh et al., the rate of adverse events in the POEM group was 17% compared to 14% in the LHM group (p = not significant). These included pneumothoraces, bleeding requiring transfusion, and mediastinitis. The LHM group had longer hospital stays compared to POEM (p < 0.00001) . AdverseAssessment of Postoperative OutcomesWhen compared with POEM in existing literature and clinical practice, the LHM had better postoperative and long-term outcomes. Most of the studies in this review reported that POEM had an increased occurrence of esophagitis compared to LHM. In a study by de Pascale et al. that assessed endoscopy at the one-year follow-up, 20% in each group completed the morphological evaluation for endoscopy, whereas 40% (eight patients) in the POEM group compared to 5% (one patient) in the LHM group had esophagitis  . This esSchneider et al. reported in their study that postoperative endoscopy was performed in 50% of POEM and 73% of LHM (p = 0.087), where esophagitis was noted to be 53% in POEM and 32% in LHM . A studyThis systematic review was developed to compare the clinical efficacy, safety, and long-term outcomes between POEM and LHM. In terms of efficacy, Eckardt score reduction pre- and post-procedure and QoL metrics were observed to be similar, with no statistical significance between both procedures. When it comes to safety, POEM has the upper hand in procedure time. However, the rate of adverse events and length of hospital stay were not significant. Postoperative outcomes, including esophagitis and the development of GERD, were noticed more in POEM patients than in LHM patients. Some studies suggest that the initial clinical success rate is relatively higher in POEM and that there is a better prognosis in treating patients with Chagas disease-affected achalasia and achalasia subtype III.This review will guide future surgeons and physicians in training to keep these findings in mind before selecting a procedure based on patient preference. Even though LHM is coupled with fundoplication, POEM can be considered a safe option given its duration and low rate of adverse events. Long-term outcomes must be evaluated with more RCTs and a larger sample size to have a more complete and detailed validation.


To evaluate the impact of a two-dose VarV program on varicella incidence among the whole population, considering the influence of public health and social measures (PHSMs), we extracted surveillance data on varicella cases during 2013–2022 in Minhang, Shanghai. Then, we estimated the incidence trend of varicella through interrupted time-series analyses and quantified the impact of the immunization program and PHSMs using Serfling regression. We also explored the associations between PHSMs and varicella cases. The implementation of the two-dose VarV strategy was followed by a significant decrease in varicella incidence (−1.84% per month). After one year of the program, varicella incidence was estimated at a 45.25% reduction, which was higher in children (59.12% and 54.09%) than in adults (19.49%). The decrease attributed to PHSMs was 31.26% during 2020–2022, and school closing was identified as the most relevant PHSM . These findings indicate that the two-dose immunization program has more effectively reduced the varicella incidence compared with the one-dose vaccine, and interventions like school closings are also encouraged to serve as supplementary measures to prevent varicella epidemics. Varicella is highly infectious, with the secondary attack rate in susceptible contacts ranging from 61% to 100% . AlthougActive immunization is considered one of the most effective ways to prevent varicella. The varicella vaccine (VarV) was first approved for use in the United States in 1995, and varicella cases declined by 71–84% within 5 years in surveillance areas . AlthougApart from varicella vaccinations, public health and social measures (PHSMs), such as school closures and home isolation for infected individuals, also help to control the spread of varicella . A previIn this study, the main objective was to evaluate the impact of a two-dose VarV immunization program on varicella incidence using surveillance data from 2013 to 2022 in Minhang, Shanghai. The impacts were quantified through interrupted time-series analysis and Serfling regression. In addition, as PHSMs were implemented to control the COVID-19 pandemic during 2020–2022, this study also analyzed the impact of related PHSMs on varicella incidence. These results could provide evidence for introducing a two-dose VarV strategy and taking effective measures to control varicella epidemics.Minhang District is situated in the middle of Shanghai Municipality, China, spanning across the inner, central, and outer ring roads of the city geographically. Minhang has approximately 2.65 million residents, which account for 10% of the Shanghai population. The demographic features like age structures in Minhang are consistent with those in Shanghai according to the national census. In addition, as the disease surveillance system, immunization program, and PHSMs in the pandemic in Minhang District are implemented in accordance with the relevant regulations of Shanghai Municipality, the database included in this study can be a good representation of Shanghai. Since 2006, varicella has been managed as a mandatory reporting disease in Shanghai. Local health providers and doctors are required to fill in the infectious disease report form once they diagnose patients with varicella and report to the district Center for Disease Control and Prevention (CDC) within 24 h via the surveillance system. This report form follows a national standard format and records the epidemiologic information for cases: age, sex, occupation, current home address, symptoms onset date, and diagnosis date. In 2017, varicella vaccination was adjusted into a two-dose procedure in Shanghai and has been included in the local immunization program since August 2018. The vaccination records of children are registered on the Minhang CDC Vaccine Management and Vaccination Service System, including demographic and vaccination information.The surveillance data of reported varicella cases in Minhang, Shanghai, during 2013–2022 were obtained from the Minhang CDC. In consideration of the influence of vaccination, the varicella vaccination data for birth cohorts from 2013 to 2018 were also extracted from the Minhang CDC Vaccine Management and Vaccination Service System.The two-dose VarV program was implemented in Shanghai in 2017 and has been included in local immunization program since August 2018. In this program, the first dose of the VarV is freely offered to children at 12–18 months, and the second dose is for children 4 years of age.The Oxford COVID-19 Government Response Tracker (OxCGRT) database has recorded national- and provincial-level government response data to the COVID-19 pandemic since 1 January 2020 . The OxCAccording to the implementation of the VarV strategy and PHSMs, the following three periods were defined: the one-dose VarV period, from January 2013 to October 2017 (before the two-dose VarV strategy); the early two-dose VarV period, from January 2018 to December 2019 (implementation of the two-dose VarV strategy); and the pandemic period, from February 2020 to December 2022 (PHSMs implemented for COVID-19).To calculate varicella incidence per 100,000 inhabitants, population data were obtained from the Shanghai Statistical Yearbook as a denominator , and theInterrupted time-series analysis was conducted to estimate changes in the incidence trends of varicella before and after the implementation of the two-dose VarV strategy and PHSMs ,24. SeasSerfling regression was used to quantify the impact of the two-dose VarV strategy and PHSMs, which has been frequently employed in research on communicable diseases ,26,27. BThe relationship between each PHSM indicator and the number of weekly varicella cases was examined using cross-correlation Spearman rank correlation analyses, where case figures were time-shifted against PHSM data by 10 weeks. To address the potential effect of covariates, partial correlation analyses and multiple regression were performed.p value less than 0.05 was considered statistically significant. False discovery rate (FDR) correction was performed to account for multiple testings. All statistical analyses were performed in 2023 using R software (version 4.1.3).A two-tailed From 2013 through 2022, 19,593 varicella cases were reported in Minhang District (median (IQR) age, 11 [5–24] years; 10,656 (54.39%) males and 8937 females (45.61%)) . ChildreThe coverage rate of the first dose of VarV ranged from 92.67% in the 2018 birth cohort to 97.62% in the 2014 birth cohort . The avep < 0.001), reaching 9.31 cases per 100 000 inhabitants in October 2017 (p < 0.001) was recognized following the implementation of the two-dose VarV program in November 2017. After PHSM implementation in January 2020, the monthly incidence of varicella continued to decrease , but not significantly. Sensitivity analyses showed similar results when not excluding the transition periods  in 2018–2019, 20.90%  in 2018, and 45.25%  in 2019, respectively (p < 0.001), which accounted for 40.86% of the total reduction in varicella incidence (Serfling regression was used to predict the varicella incidence from 2018 through 2022 based on the monthly incidence of varicella in Minhang during 2013–2017 . After tectively . To estincidence . Regardincidence .p < 0.001), and three indicators, including closing public transport , facial coverings , and the cancellation of public events  (p < 0.001) (p < 0.001) in multiple regression  , showed < 0.001)  and was gression .p < 0.001) during 2018–2019, which is a substantial change compared to the upward trend in the previous period . The incidence decreased by 20.90% in 2018 and 45.25% in the following year. In the PHSM period, the incidence trend of varicella continued to decrease but was nonsignificant, with a slope of −1.44% per month (p = 0.08). By assuming the influence of the two-dose VarV immunization program to be identical to the 45.25% reduction observed in 2019, the impact of PHSMs was estimated to be a 31.26% reduction in varicella incidence. More specifically, school closing was found to be most strongly associated with the incidence of varicella , and three PHSMs, including closing public transport, facial coverings, and the cancellation of public events, showed moderate correlations.The present study explored the impact of a two-dose VarV immunization program and PHSMs on varicella dynamics in Minhang, Shanghai. After the inclusion of the two-dose VarV strategy in the local immunization program, the incidence trend of varicella significantly decreased, with a slope of −1.84% per month , which suggests that substantial herd protection could be provided by vaccinating children. This herd protection has been observed for several kinds of vaccines and is crucial for maintaining and improving community and public health.Moreover, this study found that an additional decrease of 31.26% in varicella incidence may be attributed to PHSMs during 2020–2022. It is lower than that in a previous study that reported a 54% additional decrease caused by social distancing during the COVID-19 pandemic . This maAs varicella has not been officially regulated as a notifiable infectious disease in many countries, including China, the actual burden is usually under-reported . In a syThere were several limitations in this study. First, although one dose or the first dose of the VarV was found to have a high coverage level in the 2013–2018 birth cohorts, detailed data on the coverage of the second dose of the VarV in the 2016–2018 cohorts were lacking. Second, the relative impacts of the two-dose VarV program and PHSMs were difficult to distinguish, as they coincided during 2020–2022. Additionally, multiple PHSMs were applied simultaneously in this period, making it difficult to understand the relative contribution of each of these measures. However, this study utilized statistical methods such as Serfling regression and partial correlation to quantify their impacts more reliably. Third, as the surveillance data did not provide vaccination information for reported varicella cases, and no identifiable human data were included in this study, we did not match the records between varicella cases and VarV and failed to conduct the test-negative design analysis to evaluate vaccine effectiveness and reveal the epidemic of breakthrough cases. Furthermore, due to the lack of individual-level data, only population-level analyses were performed. Nonetheless, our study used a strong quasi-experimental design to assess the effect of the two-dose VarV strategy, which may minimize the bias. Finally, cost-effectiveness analyses of the two-dose VarV immunization program were not conducted in this study. As it is an important aspect of the inclusion of vaccines in immunization programs, this analysis will be needed in future studies.In conclusion, this population-based ecological study, with its long time span, complete surveillance records, and age-specific incidence rates, evaluated the population-level effect of the two-dose VarV immunization program on varicella incidence using real-world data in Shanghai, China. The results suggested that the introduction of the two-dose VarV strategy into the immunization program was associated with a substantial reduction in varicella incidence, and the reduction was larger in children than in adults. Moreover, this study identified that interventions such as school closings, as well as closing public transport and facial coverings, could effectively serve as supplementary measures to help prevent varicella.These findings provide evidence for countries and regions currently considering the inclusion of varicella vaccines in their routine immunization programs, especially in places where varicella remains a public health problem. Ongoing surveillance of varicella will be needed to describe more fully the impact of varicella vaccination programs and monitor the dynamics of varicella disease.


Post-COVID-19 syndrome (PCS) shares many features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). PCS represents a major health issue worldwide because it severely impacts patients’ work activities and their quality of life. In the absence of treatment for both conditions and given the beneficial effect of pacing strategies in ME/CFS, we conducted this study to assess the effectiveness of pacing in PCS patients.We retrospectively included patients meeting the World Health Organization definition of PCS who attended the Internal Medicine Department of Angers University Hospital, France between June 2020 and June 2022, and were followed up until December 2022. Pacing strategies were systematically proposed for all patients. Their medical records were reviewed and data related to baseline and follow-up assessments were collected. This included epidemiological characteristics, COVID-19 symptoms and associated conditions, fatigue features, perceived health status, employment activity, and the degree of pacing adherence assessed by the engagement in pacing subscale (EPS). Recovery was defined as the ability to return to work, and improvement was regarded as the reduction of the number and severity of symptoms.A total of 86 patients were included and followed-up for a median time of 10 [6–13] months. Recovery and improvement rates were 33.7% and 23.3%, respectively. The EPS score was the only variable significantly associated with recovery on multivariate analysis . Patients who better adhered to pacing (high EPS scores) experienced significantly higher recovery and improvement rates (60–33.3% respectively) than those with low (5.5–5.5% respectively), or moderate (4.3–17.4% respectively) scores.Our findings demonstrated that pacing is effective in the management of patients with PCS, and that high levels of adherence to pacing are associated with better outcomes.The online version contains supplementary material available at 10.1186/s12967-023-04229-w. According to the World Health Organization, post-COVID-19 syndrome (PCS) is defined as signs and symptoms that develop during or after an infection consistent with COVID-19, present for more than 12 weeks and are not attributable to alternative diagnoses. Symptoms may be new following initial recovery from an acute COVID-19 episode or persist from the initial illness .Given the fact that fatigue was reported to occur after several viral and non-viral infections , it is uPCS represents a major health issue worldwide because it severely impacts patients’ work activities and their quality of life . A recenPCS shares many features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is often triggered by a variety of infectious agents, especially Epstein-Barr virus , and occIn the absence of treatment for ME/CFS, preventing the exacerbation of the disease baseline symptoms and PEM occurrence constitutes the cornerstone of disease management. This is based on implementing pacing strategies that aim at coping with the decreased and inconsistent energy levels, which are constantly experienced by patients with ME/CFS . These sHowever, to our knowledge, the relevance of pacing strategies in PCS patients has not yet been assessed. Based on our positive experience with pacing at our national referral center for ME/CFS patients, we conducted this study to assess the effectiveness of pacing strategies in managing the symptoms of patients with PCS, especially in terms of reducing fatigue levels and preventing PEM occurrence.This retrospective study was approved by the Ethics Committee of Angers University Hospital (2022/174) and was conducted in compliance with the Helsinki Agreement. Data collection was approved by the French Data Protection Authority (CNIL).We retrospectively reviewed all medical records of patients diagnosed with PCS who attended the outpatient clinic of the Internal Medicine Department of Angers University Hospital, France between June 2020 and June 2022, and were followed up until December 2022. We included all patients who fulfilled the WHO definition of PCS . We exclThe initial and different follow-up assessments of all patients were standardized and conducted by the same physician. Each assessment included taking a detailed medical history and a thorough physical examination. Patients were systematically asked about their employment activity, time at the workplace and travel to and from work, sick leave, and whether they returned to work or not.At the initial assessment, all patients underwent an overall assessment of their epidemiological characteristics, the initial COVID-19 episode, and COVID 19-related symptoms and signs present for more than 12 weeks including, persistent, recurrent, and/or new-onset symptoms. Basal fatigue levels and its impact on patient activities, especially the current occupational status, were evaluated for all patients. In addition, special attention was paid for symptoms consistent with mast cell activation and those suggestive of autonomic dysfunction. At the end of the initial assessment, all patients were advised to apply pacing strategies, and were informed that the main objective of pacing is to prevent the exacerbation of symptoms, in particular fatigue and PEM occurrence, while remaining as active as possible. Pacing strategies rest on three pillars, which are as follows: 1. Staying within the limits of the energy envelope through identifying the current limits of the physical and mental functional capacity in different activities of daily living and not exceeding them, prioritizing activities, combining periods of activity with periods of rest, and splitting and switching activities. 2. Preventing worsening/relapse of symptoms and PEM occurrence. This requires identifying factors that trigger PEM such physical, mental and emotional stressors, orthostatic intolerance, hormonal factors in women, environmental factors (humidity and extreme temperatures), sensory stimuli , certain foods, infectious events, etc. In a number of patients, the onset of PEM is preceded by the appearance of new symptoms different from baseline manifestations such as mood disorders, nausea, headaches, vertigo, dyspnea, tingling or burning sensations, and others. These symptoms could be warning signals for PEM. Their identification could help preventing PEM occurrences or reducing their intensity . 3. CautFor all patients, follow-up assessments included an evaluation of self-reported health status, fatigue levels, persistent recurrent or new symptoms, the impact of the condition on patient’s activities, in particular on occupational status, and the degree of adherence to pacing strategies.The health status of patients was subjectively assessed by asking them to describe changes in their current health state since the previous assessment: recovered = 5, significantly improved = 4, slightly improved = 3, stationary = 2 or worse = 1.Fatigue was assessed in all patients by means of the Fatigue Severity Scale (FSS) . This reThe degree of adherence to pacing strategies was evaluated by means of the engagement in pacing subscale (EPS) of the Activity Pacing and Risk of Overactivity Questionnaire . This suRecovery was defined as the complete remission of symptoms, and the capacity to resume pre-illness levels of physical, cognitive, and social functioning with no further need for pacing strategies. Recovered patients were able to return to work, on a full or part-time basis. Improvement was defined as the reduction in the number or severity of symptoms, and the capacity to achieve certain pre-illness levels of physical, cognitive, and social functioning while still needing pacing strategies. Improved patients were not able to return to work.We classified the study population into 3 groups for comparative analysis: recovered patients (R group), improved patients, (I group), and patients who did not show any sign of recovery or improvement (no-R/I group).Quantitative data were presented in medians and quartiles, and were compared between two groups for univariate analysis using a Student’s t-test or a Mann–Whitney test according to distribution normality, assessed by using the D’Agostino-Pearson test. Comparison of quantitative data between three groups was performed by using an ANOVA or a Kruskal–Wallis test according to the normality of distribution. Qualitative data were presented as absolute values and percentages, and were compared using the Fisher’s test or Chi-square test as appropriated. Multivariate analysis was performed by means of binary logistic regression on variables associated with recovery by comparing between R group and no-R/I group patients. The variables included in the model were age, sex, and those showing significant statistical difference between R and no-R/I groups in univariate analysis. The odds ratios (OR) were presented with a 95% confidence interval (CI). Time-to-event curves for cumulative incidence of improvement or recovery were presented as Kaplan–Meier curves, and compared with a log-rank test. Loss of follow-up was censored. The alpha risk was set at 5%. The analyses were performed using Graphpad Prism v6.01  and Jamovi software v2.3.9.Among the 106 patients who fulfilled the inclusion criteria, 20 patients were excluded . In total, 86 patients were included with a male to female ratio of 1:4.4. The median age at disease onset was 41 33–48] years, and the median time of follow-up was 10 [6–13] months. Fatigue was the most frequent symptom, reported by 84/86 (97.7%) patients, followed by myalgia  and cognitive impairment . PEM was found in 32/86 (37.2%) patients  . However, the median FSS scores at last assessment were significantly higher in the no-R/I group compared to the R and I groups, and differed significantly between the 3 groups  and low (< 3.0) EPS scores, high scores (≥ 4) were significantly associated with a higher reduction in FSS scores (p < 0.0001 for both comparisons) and with higher self-reported health status scores (p < 0.0001 for both comparisons). Moderate and low EPS scores did not significantly differ in terms of reduction in FSS scores or self-reported health status scores  patients with high scores, versus 1/23 (4.3%) and 1/18 (5.5%) in patients with moderate and low scores, respectively (p < 0.0001 for both comparisons). Furthermore, improvement was observed in 15/45 (33.3%) patients with high scores, versus 4/23 (17.4%) and 1/18 (5.5%) in patients with moderate and low scores, respectively  patients, 5/6 (83.3%) of whom had high EPS scores. At 6-month follow-up, an improvement was observed in 32/49 (65.3%) patients, 29/32 (90.6%) of whom had high EPS scores.Post-COVID-19 syndrome is a common condition that affects approximately 10–35% of COVID-19 non-hospitalized patients –4, and rThe study included 86 PCS patients with the median age at disease onset was 41 [33–48] years, and median time of follow-up was 10 [6–13] months. The higher prevalence of women (81.4%) in the current study was comparable to that previously reported . FatigueWe observed a relatively high recovery/improvement rate  after pacing implementation. About a third of patients  experienced recovery and returned to work, 10 (34.5%) of whom were able to return to full-time work and the rest returned to work on a part-time basis. Twenty (23.3%) patients showed improvement in their health status with a reduction in the number and severity of their symptoms enabling them to achieve certain levels of everyday activities using pacing.The comparison between the R and no-R/I groups showed that, despite the fact that they were different on univariate analysis in terms of female sex, diagnostic delay, presence of cognitive impairment, and EPS score, the only variable that was significantly associated with recovery on multivariate analysis was the EPS score .In order to assess the effectiveness of pacing strategies in the management of PCS patients, we compared the groups of recovered, improved, and non-recovered/improved patients in terms of fatigue levels, fatigue improvement, and perceived heath status. Fatigue levels were measured by means of the FSS, fatigue improvement was evaluated by the reduction in the baseline FSS scores at the last assessment, and the perceived health status by using the self-reported health status questionnaire. Included patients had severe baseline fatigue levels as shown by the high baseline FSS scores with no statistical difference between the 3 groups of patients Table. As expeIn order to appreciate whether the degree of pacing adherence has an impact on fatigue levels, fatigue improvement, perceived heath status, and recovery rate, we used the 5-item engagement in pacing subscale . We demoOn the other hand, it is important to mention that pacing is not an avoidance behavior, but a series of strategies that aim to prevent both overexertion and underexertion. In other words, pacing has the objective of maintaining the different activities within the limits of the available energy reserve. To attain this goal, pacing strategies require continuous adaptation and adjustment of the provided effort according to perceived energy levels. As a result of these strategies, energy levels will gradually increase with a reduction in the perceived fatigue, thus allowing patients to progressively conduct higher levels of physical and cognitive activities  and to iThe main question that arises is how does pacing produce its beneficial effects in PCS and in ME/CFS. One possible explanation may be the imbalance in the cytokine activities. It is now known that patients with PCS –45, likeFor instance, a previous study on patients with CFS demonstrated that pro-inflammatory cytokines levels failed to decrease 48 h after moderate exercise, and concluded that the severity of post-exercise symptom exacerbation in severely fatigued patients was linked to cytokine activity . SimilarA further possible explanation for the beneficial role of pacing in PCS and ME/CFS could be related to the mitochondrial dysfunction, which is known to be linked to fatigue . Both coOne criticism of pacing is that it may cause deconditioning, and some authors have speculated that deleterious sequelae of exercise in a group of CFS patients were due to or maintained by physical and cardiovascular deconditioning. They concluded that physical reconditioning by means of a graded exercise program help improve the physical function of these patients , 59. NevOne source of weakness in this study was its retrospective character. However, all included patients were diagnosed, evaluated, and followed up by the same physician and underwent the same standardized procedure at the initial and follow-up assessments. Future prospective studies are required to confirm findings of the current work. Another limitation is the use of self-reported questionnaires to assess pacing and global health status, which could be a potential bias due to the subjectivity of these measures. However, in addition to these subjective measures, we set returning to work as an obligatory criterion for defining recovery, and used it to objectively assess the effect of pacing adherence on fatigue levels and health status perception. In this respect, we encourage researchers to adopt the employment status as an objective tool for assessing the evolution of subjective symptoms, in particular the fatigue. Lastly, making distinctions between the concepts of recovery and improvement in assessing pacing relevance could give more weight to our findings.To the best of our knowledge, our study is the first to assess the relevance of pacing in the management of patients with post-COVID syndrome. We observed a high recovery and improvement rates among these patients after the implementation of pacing strategies. We also demonstrated that high adherence to pacing strategies was effective for improving the overall health status, thus enabling patients to restore pre-illness performances and to return to work. The more the patient adheres to pacing, the higher the rate and the degree of recovery, and the more rapid the improvement. These findings emphasize the relevance of pacing in the management of PCS as is the case for ME/CFS. They further highlight the similarity between both conditions, and represent a strong argument for extending the use of pacing to PCS patients. To do this, it is important to raise awareness among primary care physicians about the substantial role of pacing in PCS management and establish educational programs to teach patients how to apply pacing strategies.Additional file 1: Table S1. Characteristics of the study population.Additional file 2: Figure S1. Pacing Strategies for Managing Post-COVID-19 Syndrome.Additional file 3: Figure S2. Assessment of Pacing Adherence in Patients with Post-COVID-19 Syndrome.


The study found that the estimated values were in good agreement with the reported experimental data, as evidenced by a high correlation coefficient (R) and a low Mean Relative Absolute Error of greater than 0.999 and less than 0.004, respectively. In addition, the results of the used SGB model were compared to the results of SVM, GA-SVM, GA-LSSVM, CSA-LSSVM, GMDH-PNN, three based ANNs, PSO-ANN, GA-ANN, ICA-ANN, TLBO-ANN, ANFIS, ANFIS-ACO, ANFIS-DE, ANFIS-GA, ANFIS-PSO, and MGGP models. In terms of the accuracy, the SGB model is better and provides significantly lower deviations compared to the other techniques. Also, an evaluation was conducted to determine the importance of each variable in predicting surface tension, which revealed that the most influential factor was the mole fraction of IL. In the end, William’s plot was utilized to investigate the model's applicability range. As the majority of data points, i.e. 98.5% of the whole dataset, were well within the safety margin, it was concluded that the proposed model had a high applicability domain and its predictions were valid and reliable.Precise estimation of the physical properties of both ionic liquids (ILs) and their mixtures is crucial for engineers to successfully design new industrial processes. Among these properties, surface tension is especially important. It’s not only necessary to have knowledge of the properties of pure ILs, but also of their mixtures to ensure optimal utilization in a variety of applications. In this regard, this study aimed to evaluate the effectiveness of Stochastic Gradient Boosting (SGB) tree in modeling surface tensions of binary mixtures of various ionic liquids (ILs) using a comprehensive dataset. The dataset comprised 4010 experimental data points from 48 different ILs and 20 non-IL components, covering a surface tension range of 0.0157–0.0727 N m These molten salts, which consist of organic cations and organic/inorganic anions, have gained popularity in various industries as a new class of compounds for diverse applications. Due to their bulky and asymmetrical cation structure2, ILs have a low tendency to form an ordered crystal and thus remain in a liquid state at ambient temperature.In the past few years, there has been a surge of interest in ionic liquids (ILs) among scientists, engineers, regulators, and policy makers worldwide5. ILs are often referred to as “designable materials” because their properties can be tailored for specific processes by making structural modifications to the cation or anion6. At present, ILs are being used for various applications, including but not limited to Enhanced Oil Recovery (EOR)7 process, extraction processes11, catalytic reactions12, separation processes15, electrochemistry16, lithium batteries17, biomass conversion18, desulphurization19, coal dissolution20, bitumen processing22, crude oil dissolution24, asphaltene dissolution25, and crude oil/water IFT reduction26.The exceptional properties of ILs, such as their good catalytic properties, low vapor pressure, nonflammability, high solvation capacity for various organic compounds, and high thermal and chemical stability, make them promising sustainable alternatives to traditional materials in a wide range of processes27, such as in EOR processes in reservoirs. This is of great importance from both academic and industrial perspectives.Having a comprehensive understanding of the chemical, physical, and thermodynamic properties of ILs or their mixtures with other compounds is crucial, especially since a significant percentage of industrial applications of ILs involve mixtures28 of ILs and their relevant mixtures. It plays an essential role in the appropriate design and operation of upcoming industrial processes that involve mass transfer, such as distillation, extraction, and absorption29. In the petroleum industry, surface tension is particularly important for designing fractionators, absorbers, separators, two-phase pipelines, and assessing reservoirs30. This is because it significantly affects mass and heat transfer at the interfaces31. Interested readers are referred to Tariq et al.32 who provide a detailed explanation of why surface tension of ILs is crucial.Surface tension is a critical macroscopic physical property33. Therefore, it is important to have a reliable and powerful scheme for predicting surface tension34, as experimental measurements are not always feasible for all ILs and their mixtures with various substances.Due to the infinite number of possible systems, it is impractical to experimentally measure the surface tension of every possible IL and its mixture with other compounds. Additionally, empirical measurements can be expensive, time-consuming, and susceptible to non-negligible uncertainties32 and Gharagheizi et al.35 have explored this topic. However, Oliveira et al.3 used the Soft Statistical Associating Fluid Theory (soft-SAFT) equation of state and the density gradient theory (DGT) to model the surface tension of mixtures containing [Cnmim][NTf2] ILs with different alkyl chain lengths . A model based on a cubic equation of state and on the geometric similitude concept is proposed by Cardona and Valderrama36 to calculate the surface tension of pure substances and mixtures containing organic substances, water, and ILs. The model has been extended to binary and ternary mixtures using simple mixing and combining mixing rules without interaction parameters, so the predictive capabilities of the model are guaranteed. The mixtures are composed of organic solvent + IL and water + ILs. Equations of state (EOS) methods are only applicable to systems for which they have been calibrated. Typically, EOS models rely on adjustable parameters that must be optimized based on experimental data points. Without experimental data and calibrated parameters, these models cannot be fully trusted, and the process of calibration can be time-consuming and complex37. Therefore, it is essential to focus on developing and utilizing general models capable of predicting the thermophysical properties of these systems in general, and surface tension in particular.Although there have been some attempts to calculate the surface tension of pure ILs using different methods, there are few studies available in the literature that focus on predicting the surface tension of mixtures containing ILs. Reviews conducted by Tariq et al.38. In the field of ILs, several groups around the world have accomplished several studies on the application of the Artificial Neural Networks (ANNs) for prediction the properties of the ILs and their related mixtures such as thermal conductivity of ionic liquids39, solubility of supercritical carbon dioxide in ILs40, ternary electrical conductivity of IL systems41, bubble points of ternary systems involving ILs42, viscosity of ternary mixtures containing ILs43, binary heat capacity of mixtures containing IL44 and melting point of ILs45. Also, recommended published papers are47; for a more applications of different machine learning approaches in the field of ILs.During recent years, soft computing methods have drawn researchers' attention by virtue of their capability to model and tackle difficult issues that were formerly problematic or impractical to solve48 utilized a group contribution method based on ANNs to estimate surface tension values of pure ILs, while Atashrouz et al.49 developed a mathematical model using Least Square Support Vector Machines (LSSVM) to predict surface tension values of pure ILs. Obaid et al.50 used AdaBoost with different base models, including Gaussian Process Regression (GPR), Support Vector Regression (SVR), and Decision Tree (DT) to predict surface tension of different ILs. A review of the current literature reveals that there are only a few studies that have utilized different soft computing techniques to predict surface tension values for binary systems that contain ILs. These methods will be discussed in detail below.Various soft computing methods have been employed by researchers to predict the surface tension of pure ILs. For example, Lazzús et al.46 utilized Support Vector Machine (SVM) and LSSVM models combined with Coupled Simulated Annealing (CSA) and Genetic Algorithm (GA) to predict surface tension of binary mixtures consisting of 31 different IL mixtures and 748 data points. The input parameters of their models included temperature, IL properties, and non-IL properties. They found that the CSA-LSSVM model outperformed other models in view of statistical parameters. In another inquiry51, they used an ANN model based on the same data points and input parameters. Their model accurately predicted surface tension in terms of statistical analysis. Based on the same dataset and input variables, Setiawan et al.33 suggested different ANNs disciplined by four optimization algorithms, namely Teaching–Learning-Based Optimization (TLBO), Particle Swarm Optimization (PSO), GA, and Imperialist Competitive Algorithm (ICA), to estimate surface tension of the binary ILs mixtures. Atashrouz et al.52 used GA-LSSVM, GA-SVM, and Group Method of Data Handling Polynomial Neural Network (GMDHPNN) models to estimate surface tension of binary mixtures containing ILs based on 573 data points and 28 different mixtures. Their input data included temperature and properties of ionic and non-ILs. They concluded that GA-LSSVM and GA-SVM models had better prediction ability compared to GMDH-PNN model. Lashkarbolooki53 used an ANN model based on 836 data points and 32 different mixtures. The input parameters of the model included temperature, melting temperature, mole fraction, and molecular weight of ionic and non-ILs. Shojaeian and Asadizadeh54 proposed an ANN model to predict surface tension of binary mixtures containing ILs based on 1537 data points regarding 33 binary mixtures. In their study, various approaches were developed by utilizing physical properties such as temperature, reduced temperature, critical temperature, critical pressure, critical volume, molecular weight, acentric factor, and critical compressibility factor, along with two distinct mixing rules, as input parameters. In addition, they utilized five different intelligent methods, including Adaptive neuro-fuzzy inference system (ANFIS), ANFIS optimized with Ant Colony Optimization (ANFIS-ACO), ANFIS optimized with Differential Evolution (ANFIS-DE), ANFIS optimized by GA (ANFIS-GA), and ANFIS optimized by PSO (ANFIS-PSO), to predict the surface tension values for the binary mixtures of interest. The results were then compared to those obtained using an ANN model, which was found to have the highest level of accuracy as compared to the other five ANFIS based models. Esmaeili and Hashemipour55 used Multi-Gene Genetic Programming (MGGP) to develop correlations for predicting surface tension in binary mixtures containing ILs based on 1414 data related to 37 binary mixtures have been gathered from literature. They presented two correlations for predicting of surface tension of IL and non-IL mixture using just temperature and mole fraction of IL component.Soleimani and his colleaguesDespite the efforts to create precise models, the review of literature revealed that there is a much larger amount of experimental surface tension data available for binary mixtures containing ILs than what was used in previous studies. Therefore, it is crucial to conduct an in-depth literature search to gather a comprehensive database of experimental surface tension values, which is necessary for developing a comprehensive predictive model.56 has emerged as one of the potent methodologies for predictive data mining. The concept of algorithm for GB Trees rooted in application of boosting method to regression trees. A new version of GB Tree model named stochastic gradient boosting (SGB) tree model, introduced by Friedman57, which is appeals to scientific communities and engineers due to enjoys several merits, for instance it works effectively on vast data sets, it is fast, relatively simple, easy to use and requiring the tuning a few parameters. The capability of capturing non-linear associations between inputs and target is one of the main strengths of this improved heuristic model, due to complex inherent structure of real-world data. Also, this promising machine learning scheme is robust to variable outliers, variable collinearity and missing data. Boosted regression tree based models have performed and applied well in various study domains such as carbon dioxide-oil minimum miscibility pressure prediction, carbon dioxide solubility in polymers forecasting58, estimation of interfacial tension for geological carbon dioxide storage59, predicting carbon dioxide solubility in aqueous amine solutions61.Over the past few years, Gradient Boosting (GB) Tree model developed by Friedman et al.SGB scheme with 18 commonly used computational models. Besides, the effectiveness of each of the input variables on the output of the SGB model, i.e. surface tension, is assessed. Finally, an outlier diagnosis method is employed to examine any ambiguous or inconsistent experimental data.As far as we are aware, there is no study on the application of the properties prediction of the surface tension of ILs mixtures using the DT based approaches. Thus, for the first time, this study will present an SGB scheme for predicting binary surface tension values of IL systems using a comprehensive dataset of 4010 experimental surface tension values of binary mixtures containing ILs. Furthermore, we will compare the performance of 62, cover temperatures between 278.15 and 348.15 K where the pressure was held constant at atmospheric condition. In total, data points cover 122 distinct binary mixtures comprising 48 different ILs and 20 various non-IL components (water and 19 various organic compounds). The detailed information about binary mixtures, ILs and non-IL constituents presented in the supplementary information  for creating the SGB tree model took from the NIST Standard Reference Databaseon Table .51, i.e. the temperature  is a novel branch of traditional Gradient Boosting (GB) developed by FriedmanGradient Boosting (GB) is an ensemble method that transforms weak hypotheses into strong ones by minimizing the loss of the model using a gradient descent-like procedure. GB takes a collection of weak learners, such as decision trees, and adds them to the model to avoid overfitting. Trees are created in a stage-wise fashion, and future weak learners focus more on examples that the previous ones misclassified. The final output of the model is improved by adding the output of the updated tree to the output of the existing sequence of trees.The training procedure employed in SGB can be examined through the flowchart depicted in Fig. 63. Additional information on the mathematical aspects of the SGB model can be found in the literature77.In this study, the SGB algorithms have been executed based on the instructions provided in Friedman’s worksThe current study utilized the SGB tree model to predict the surface tension of binary mixtures of ILs, as previously mentioned. It is crucial to carefully set the hyper-parameters to ensure the SGB model's maximum generalization ability. Among these parameters, the learning rate (η) has a significant impact on the final outcome. Through an extensive trial and error process, the optimal value for the η was found to be 0.57. The model's performance improves when using a η value of 0.57, as shown in Fig. Figure 78.Various criteria were employed to evaluate the performance accuracy of the SGB tree method. The statistical analysis results were measured in terms of several parameters, including Mean Square Error (MSE), Root Mean Square Error (RMSE), Mean Absolute Error (MAE), Mean Relative Squared Error (MRSE), Mean Relative Absolute Error (MRAE), Relative Absolute Error (RAE), Correlation Coefficient (R), Bias Factor (Bf), and Accuracy Factor (Af). These parameters were calculated using Eqs. –10) as  as 10) aRegression plots can be used to validate models, and Fig. The SGB model provided highly accurate predictions of the surface tension of binary mixtures, as indicated by the slope value being close to 1 and the intercept having a negligible value.Another crucial aspect of creating an accurate predictive model is the model's ability to estimate experimental binary surface tension data accurately, both overestimating and underestimating, across a range of input parameter variations. Figure 2, Bf, and Af, for both the training and test subsets of the SGB tree model, as well as for all the data sets. The results in Table f was obtained 1.0002301 which indicate that the predictions were 0.02301% larger than experimental values, while Af of 1.0039883 means that, on average, the predicted value is 0.39883% different  from the experimental value. These results demonstrate the SGB tree model's acceptable accuracy in determining the surface tension of 122 distinct binary mixtures under different conditions. Thus, based on the satisfactory results obtained, it can be concluded that the SGB tree model is a reliable method for predicting the essential physical property of surface tension for binary IL mixtures. Interested readers could refer to the references80 for detailed discussions of these statistics; in the circumstance of estimation issues; various statistical parameters are as well reviewed in the references82.As mentioned, to ensure that the SGB model can generalize, the collected dataset was divided into two segments: the training set and the test set. The training set was used to fit the SGB model, while the test set provided an unbiased assessment of the model's accuracy. Table The cumulative frequency of errors versus RAE% is depicted in Fig. 83. Figure 55, who utilized the Pearson method to evaluate the efficacy of various parameters in this context. The variables of The SGB algorithm provides the relative influence of each variable on the model’s output, which is a benefit inherent in the decision tree. The variables’ influence is rested on averaging the amount that each variable is decided on for splitting, weighted by the squared improvement to the model as a consequence of each splitIn order to conduct a thorough investigation into the surface tension of binary mixtures containing ILs using the SGB model, a sensitivity analysis was performed to determine how input parameters such as The values of 46 utilized 748 experimental data points to predict the surface tension of binary mixtures that included ILs using SVM based methods. They conducted a study to optimize the three parameters of the SVM algorithm for predicting surface tension. This was done using a user-defined approach based on prior knowledge and experience. Additionally, GA and CSA algorithms were utilized to find an improved combination of the two hyper parameters embedded in the LSSVM model. The aim was to maximize the generalization performance of the LSSVM model in predicting surface tension. By employing these optimization techniques, the researchers sought to enhance the accuracy and effectiveness of the LSSVM model for surface tension prediction. With the same data set, an ANN51 model with a structure containing twelve neurons in it’s both hidden layers and trained by trainbr function was proposed for the purpose of predicting surface tension of binary mixtures. Table −1 and temperature range of 278.15–348.15 K. This data set comprises 122 binary systems, with 20 non-IL components and 48 IL components. On the other hand, the ANN, SVM, GA-LSSVM, and CSA-LSSVM were created based on a smaller data set of 748 points, covering 31 binary systems, with 9 non-IL components and 15 IL components. This data set covers a surface tension range of 0.0157–0.07135 N m−1 and temperature range of 283.1–348.15 K.Hashemkhani et al.53, SVM46, CSA-LSSVM46 and GA-LSSVM46 models based on 21 different studied binary mixtures that were common in these models, the MRAE in percent was computed for each binary system. It should be mentioned that instead of 53. He suggested an ANN model for binary surface tension prediction, which comprised one hidden layer with 16 neurons based sing 836 binary surface tension data points obtained within a temperature range of 278.15–348.1 K, and it includes a total of 11 ILs and 11 non-ILs, resulting in 32 binary IL/non-IL systems. The network was trained by trainlm function with 836 collected data points. Table Also, to compare the SGB Model with ANN52 as well as SGB model for 13 different binary mixtures that were common in these models, are tabulated in Table 52 models. It is also worth highlighting that Atashrouz and colleagues52 developed two separate models using different datasets; one for ILs mixed with water and another for ILs mixed with organic compounds. In contrast, the SGB model proposed in this study is a unified model that covers both binary systems, including both ILs mixed with water and 19 different organic compounds. This indicates that the SGB model has broader applicability and is more comprehensive than the previous models developed by Atashrouz et al.52. Moreover, it should be emphasized that the models proposed by Atashrouz et al.52 was constructed using 573 binary surface tension data points that were collected within a temperature range of 283.15–342.8 K, and covering a range of surface tension values from 0.0218 to 0.07160 N M−1. The models include 20 ILs and 8 non-ILs, resulting in a total of 28 binary IL/non-IL systems.Moreover, the computed MRAE% values of three models based on Neural Network (NN) and SVM, viz. GMDH-PNN, GA-SVM and GA-LSSVM which were proposed by Atashrouz et al.33 in terms of R2 and MSE values reported in Table 33 was identical to that in Hashemkhani et al.’s investigation46.In addition, the capability of the SGB model for the purpose of predicting surface tension of mixtures in this study was also compared to the ANN models optimized with GA, PSO, ICA, and TLBO algorithms proposed by Setiawan and colleagues55 in terms of their ability to predict the surface tension of 9 binary systems that were present in both models. Table Furthermore, a comparison was made between the SGB model and the MGGP model54, including ANFIS, ANFIS-ACO, ANFIS-DE, ANFIS-GA, ANFIS-PSO, and ANN, with the SGB model. The authors used 1537 data points from 33 binary mixtures comprising 15 unique IL components and 11 individual non-IL substances to predict surface tension across a temperature range of 278.15–338.15 K, with a surface tension range of 0.0189–0.0727 N M−1. To prepare the input parameters, they used physical properties such as temperature, reduced temperature, critical temperature, critical pressure, critical volume, molecular weight, acentric factor, and critical compressibility factor, as well as two different mixing rules. The ANN models proposed by Shojaeian and Asadizadeh had one hidden layer with 10 neurons and used the training function trainlm. In the ANFIS-based models, ACO, DE, GA, and PSO algorithms were introduced to obtain the optimum parameters. Table 54.Finally, Table 84. Outliers refer to observations that deviate from the bulk of data obtained under the same conditions85. It is common to encounter outliers or doubtful data in projects involving data collection, and this is especially true for large datasets like the one used in this study. In addition to errors in experimental measurements, data entry errors can also contribute to the presence of outliers, particularly when data is recorded manually86. To develop reliable predictive models, it is essential to have accurate data points from experimental tests87. However, even if the data is obtained from reputable sources, errors in experimental measurements may affect the model's prediction capability. Removing potential outliers can enhance model performance, but this requires a novel technique to identify them. The Leverage approach is used in this study to assess the quality of experimental data points and determine the best model's range of applicability.The detection of outliers is crucial in the development of mathematical models89:The leverage approach involves the use of a hat matrix (H) to calculate the hat indices or leverage of data points as follows89:The equation given uses a two-dimensional matrix X with N rows (representing the data points) and k columns (representing the model parameters), along with a transpose multiplier t. The hat values of data are represented by the diagonal components of the H matrix, which are obtained using Eq. . These HThe hat index of the ith data point is denoted by Hii in the equation given above.89.The Leverage approach utilizes a warning leverage parameter (Based on Fig. SGB tree model in handling 122 different types of binary systems, in predicting of surface tension of binary mixtures containing ILs based on a comprehensive data set of 4010 experimental data points consists of 48 different ILs and 20 various non-IL components, was examined. In the SGB tree model, the system conditions of temperature and IL component composition as well as molecular weight of IL and non-IL components, density of IL component and normal boiling point of non-IL component are used as input variables. It is notable that SGB tree model has been used for the first time for prediction/estimation of properties of mixtures especially those containing IL. Based on the results presented, the main contributions of the current research include:Experimental surface tensions of studied binary systems show a consistency and good agreement with results of SGB tree model.The MRAE and R values of the SGB models for predicting of mixtures containing ILS were nearly 0.003989 and 0.99923 respectively.SGB method is visibly superior to the SVM, GA-SVM, GA-LSSVM, CSA-LSSVM, GMDH-PNN, three based ANNs, PSO-ANN, GA-ANN, ICA-ANN, TLBO-ANN, ANFIS, ANFIS-ACO, ANFIS-DE, ANFIS-GA, ANFIS-PSO, and MGGP models in the respect of accuracy.The comparison between the results of 18 various computational approaches reveals that the Furthermore, with the bar graph of the predictor importance, the mole fraction of IL component was recognized as the variable that makes the major contributions to the prediction of the dependent variable of interest.The Leverage mathematical algorithm was employed to detect outliers and assess the applicability domain of the SGB model proposed in this study. The analysis revealed that a very small percentage, specifically 1.5%, of the overall dataset was deemed questionable and did not meet the expected criteria.In addition to the high accuracy of the predicted surface tensions, the most important advantage of the model of binary surface tensions proposed in this study, is that the proposed SGB tree model constructed exclusively based on experimental data which makes it attractive for scientists and engineers to apply such ensemble learning tool for rough estimation of the surface tension of any desired binary mixtures comprised of ILs.The findings of this study can be used in industries that use ILs, particularly in the design and optimization of new processes on an industrial scale.Due to the largest available dataset was applied, a dependable technique was put forth to predict the surface tension of numerous binary mixtures containing various ILs. Nevertheless, it has a limitation: although the SGB method is broadly applicable, its predictive ability is confined to binary systems that closely resemble those used to create the model. It is not advisable to apply the developed tool to binary systems that are entirely dissimilar from the ones studied, though it may provide a rough approximation of the surface tension of such mixtures.Future directions of this work could involve applying the developed models to predict the surface tension of new binary mixtures containing different ILs such as phosphonium and sulfonium based-ILs and evaluating their performance against experimental data. Additionally, the developed model could be used in process optimization and design for various industrial applications. Further research could also investigate the feasibility of applying these models to ternary and multicomponent systems containing ILs. More research could also investigate the feasibility of applying this model to other types of properties of mixtures containing ILs.The capability of the Supplementary Information.


Psoriasis is an important issue in daily dermatological practice. Not only is it an aesthetic defect but it is also a matter of decreased life quality and economic burden. However frequent, the pathogenesis of psoriasis remains uncertain despite numerous investigations. Gasdermins are a family of six proteins. Gasdermin D (GSDMD) is the best-studied from this group and is involved in the processes of inflammation, proliferation, and death of cells, especially pyroptosis. GSDMD has never been studied in psoriatic sera or urine before. Our study involved 60 patients with psoriasis and 30 volunteers without dermatoses as controls. Serum and urinary GSDMD concentrations were examined by ELISA. The tissue expression of GSDMD was assessed by immunohistochemistry. The serum-GSDMD concentration was insignificantly higher in the patients than controls. There were no differences in the urinary-GSDMD concentrations between the patients and controls. Strong tissue expression of GSDMD was significantly more prevalent in psoriatic plaque than in the non-lesional skin and healthy skin of the controls. There was no correlation between the serum-GSDMD concentrations and the psoriasis severity in PASI, age, or disease duration. Taking into consideration the documented role of gasdermins in cell proliferation and death, the increased expression of GSDMD in psoriatic skin may demonstrate the potential involvement of this protein in psoriasis pathogenesis. Neither serum, nor urinary GSDMD can be currently considered a psoriasis biomarker; however, future studies may change this perspective. One of the greatest mysteries of contemporary dermatology remains psoriasis. However frequent and well-studied, there is still much to discover about its pathogenesis, its potential biomarkers, and the successful methods of its treatment. There are 125 million people suffering from psoriasis worldwide [What is known about psoriasis pathogenesis is that there are, in general, three links influencing each other mutually: genetic background, immune disturbances, and modifying external stimuli ,4. AfterGasdermin D (GSDMD) is a member of the gasdermin-proteins family . GSDMD, GSDMD is probably the best-studied of all the gasdermins. Its encoding gene is located on chromosome 8q24 . GSDMD eTaking into account the documented role of GSDMD in cell death, proliferation, and differentiation , we becaThe suspected involvement of GSDMD in psoriasis pathogenesis is presented in Gasdermins have been poorly investigated in psoriasis so far and both the serum and urinary concentrations and tissue expression of GSDMD in immunohistochemistry have never been studied in this disease. Our team has already assessed all gasdermins in the mentioned biological materials. Apart from the tissue and serum, we chose urine for the investigation because it is easy, painless, and cheap to collect; thus, it would be an ideal fluid for biomarkers’ assessment. Hereby, we present our results regarding the possible role of GSDMD in psoriasis pathogenesis, with reference to its clinical application.The basic characteristics of the patients and controls are presented in p > 0.05).There was no statistically significant difference between the patients and controls in terms of age, gender, or BMI . There was no significant correlation between the serum concentration of GSDMD and PASI, BMI, age of patients, or psoriasis duration.There was no significant difference between men and women in serum-GSDMD concentrations  and from the healthy skin in the control group (p < 0.001); none of the samples from the control group exhibited strong GSDMD expression. There was no significant difference between the psoriatic plaque, non-lesional skin in patients, and the healthy skin of the controls in terms of the number of samples with moderate GSDMD expression (p > 0.05). In the group of samples originating from the psoriatic plaques, there was a significantly lower number of samples that lacked GSDMD expression than in the group from the non-lesional patients’ skin (p < 0.01) and from the healthy skin of controls (p < 0.001)  .p < 0.01 and p < 0.05, respectively).After the division into three subgroups according to PASI , we did GSDMD has gained much attention lately. Its role has been proven crucial in the pathogenesis of many disorders, such as infections , cardiovSerum and urine, as well as the tissue expression of GSDMD in immunohistochemistry, have never been evaluated in psoriatic patients; thus, we are the first to report on this matter.The expression of the GSDMD gene has been assessed before in several dermatoses, including psoriasis, on a very small number of samples in the study by Zhang et al. . They reHowever, we did not obtain a statistically significantly higher level of GSDMD in patients’ sera compared to the controls and no significant differences were found. In the urine, we found a higher expression of this protein in psoriatic plaques, which points to its potential role in psoriasis.Given the proven role of gasdermins in cell proliferation and death, and the initial part of its activation, which is convergent with the initial stage of psoriasis pathogenesis, the upregulation of GSDMD in psoriatic patients compared to the controls without psoriasis demonstrates the potential involvement of this protein in the pathogenesis of psoriasis. It is likely that GSDMD may be its new link. Our suggestion is that the activation of inflammasomes, and then caspases, results in the cleavage of GSDMD, leading to the release of pro-inflammatory cytokines, which are further able to stimulate epidermal proliferation. It has been proven that inflammasome complexes may initiate non-canonical pathway, leading to the release of GSDMD. At the same time, caspase 1 activates IL-1β, which stimulates IL-17, which further promotes epidermal proliferation . To suppAnother link between psoriasis and GSDMD is NETosis. GSDMD has been documented to participate in this process  and it hOur study indicates that GSDMD is, indeed, supposedly involved in the complex pathogenesis of psoriasis. However, considering our results, serum or urinary GSDMD cannot become a psoriasis biomarker at this time because both were insignificantly elevated in patients. Moreover, we cannot assume that GSDMD can serve as a marker of psoriasis severity because there were no correlations or significant differences in its serum concentration depending on PASI. Considering that our study is the first of this kind, we have no data on psoriatic patients to compare with.The serum concentrations of GSDMD were independent of gender and psoriasis duration; therefore, GSDMD seems to be potentially engaged in both sexes equally, but currently, it cannot serve as a marker of the time that patients suffer from this dermatosis.The only correlation we found was the negative one between GSDMD and ALT activity. It may, perhaps, point to the role of GSDMD in liver pathology in psoriatic patients; nevertheless, it is too early to state that and future studies are required. Psoriasis has been linked to non-alcoholic fatty liver disease (NAFLD) and such patients have a two-fold increased odds of concomitant NALFD, which is, in addition, associated with psoriasis severity . The oriAs for the limitations of our research, we enrolled a relatively small number of participants of only one ethnicity. The other aspect is the limited data on the kidney metabolism of GSDMD, which may cause difficulties in the interpretation of the results; however, this is why we presented our results both as absolute values of urinary-GSDMD concentrations, as well as a ratio of the urinary/creatinine concentration. Obviously, further studies on bigger samples are needed to better explore this topic.In total, 60 patients (21 women and 39 men) with active plaque-type psoriasis were enrolled in the study, at the mean age of 50 ± 2.34 years old, as well as 30 sex- and age-matched volunteers without dermatoses and a negative family history of psoriasis. All participants signed informed consent forms before the initiation of the study. The inclusion criterion was adult patients with plaque psoriasis. The exclusion criteria from the study were as follows: age under 18 years old, pregnancy, types of psoriasis other than plaque, dietary restrictions, intake of oral medications at least 3 months prior to the study, malignant neoplasms, and renal impairment. The collection of all the samples took place between 8 July 2020 and 20 April 2023. The severity of the psoriatic skin lesions was assessed using the Psoriasis Area and Severity Index (PASI) and was always performed by the same dermatologist. The study group was divided into three subgroups depending on the severity of the disease: PASI I (PASI < 10)—mild psoriasis, with 16 patients; PASI II (PASI 10–20)—moderate psoriasis, with 30 patients; and PASI III (PASI > 20)—severe psoriasis, with 14 patients. The body mass index (BMI) was calculated as weight/height2. Basic laboratory tests were performed before the study. The study was approved by the Bioethics Committee of the Medical University of Bialystok (APK.002.303.2022 and APK.002.19.2020) and was conducted in accordance with the principles of the Helsinki Declaration [g. Urine samples were taken as first-morning specimens from a mid-stream and they were centrifugated for 10 min at 2000× g. The obtained serum and urine were stored at −80 °C until further analysis. Laboratory parameters were measured using routine techniques. GSDMD concentrations were measured with an enzyme-linked immunosorbent assay (ELISA) provided by EIAab® , with a minimum detectable dose of 0.312–20 ng/mL. The optical density was read at a wavelength of 450 nm. The concentrations were assessed by interpolation from calibration curves prepared with standard samples provided by the manufacturer. All laboratory tests were performed by the same person in standardized laboratory settings.The analysis of the serum and urine was performed in 60 psoriatic patients and 30 sex- and age-matched volunteers without dermatoses. Fasting blood samples were taken using vacuum tubes. They were left to clot for 30 min before centrifugation for 10 min at 2000× ®, Saint Louis, MI, USA, HPA0444487) for 30 min at room temperature. Then, post-primary block and Novolink polymer were used . The protein expression was visualized with Novolink DAB solution and cell nuclei with hematoxylin . The expression of GSDMD was presented using a semi-quantitative method and the reaction was observed in the epidermis as follows: 0—no expression; 1—moderate, up to 30% keratinocytes, except for the stratum basale and corneum; and 2—strong, in the whole epidermis, except for the stratum corneum. Among the psoriatic plaques, 18 patients exhibited strong expression, 12 patients—moderate, and 3 patients—no expression. Among the non-lesional skin samples, 7 patients exhibited strong expression, 10 patients—moderate, and 16 patients—no expression. In the control group, 5 participants exhibited moderate expression and 15 participants—no expression. The tissue sample collection was performed in 33 patients with psoriasis and 20 sex- and age-matched volunteers without dermatoses considering that not every patient agreed to perform the biopsy. This study group was further divided, similar to the subjects who donated serum and urine, into three subgroups depending on the severity of the disease: PASI I (PASI < 10)—mild psoriasis, with 8 patients; PASI II (PASI 10–20)—moderate psoriasis, with 18 patients; and PASI III (PASI > 20)—severe psoriasis, with 7 patients. All participants did not apply any topical drugs on their skin for at least a month before the biopsy. Biopsies were taken from the trunk in all participants with a 4 mm punch after local anesthesia with 2% lignocaine. In the patients, two biopsies were taken: one from the lesional skin—the psoriatic plaque—and the other one from the non-lesional, clinically healthy skin, approximately 2 cm from the psoriatic plaque. As for the controls, one skin sample was taken from the non-lesional skin and the sampling was performed during the surgical removal of benign skin lesions. Tissue samples were then fixed in 10% buffered formalin solution. After preservation, they were embedded in the paraffin blocks and cut into 4 µm sections on silanized slides. The next step was an overnight incubation at 60 °C, deparaffinization, and rehydration of the tissues. Slides were then incubated with 3% hydrogen peroxide solution to block endogenous peroxidase and with protein block to avoid non-specific antibody binding. Next, tissues were incubated with the rabbit polyclonal anti-human GSDMD antibody  and shown as mean ± SD. The non-Gaussian data are presented as a median (full range) and were analyzed using the non-parametric Kruskal–Wallis test. Student’s This is the first comprehensive study on the possible role of GSDMD in psoriatic patients, including its serum and urinary concentrations’ application in the clinical aspect. We proved that GSDMD is significantly most-expressed in psoriatic plaques and insignificantly elevated in the serum of patients with psoriasis compared to controls without psoriasis. Understanding the role of gasdermins in the death and proliferation of cells, we propose their engagement in psoriasis pathogenesis based on the activation of caspases, which results in the cleavage of GSDMD, leading to the release of pro-inflammatory cytokines and epidermal hyperproliferation. Moreover, pyroptosis, in addition to inducing cell death, exacerbates inflammation, which, when chronically sustained, is a feature of psoriatic epidermis. On the other hand, neither serum, nor urinary GSDMD seem, at the moment, to become markers of psoriasis or its severity.Serum GSDMD is the subject of ongoing patent application no P.445837.