Univariate analysis showed a significant association between large tumor size, elevated Ki67, c-MET values and increased risk of recurrence or death. The multivariate COX regression model showed that tumor size and high c-MET expression were independent predictors of DFS (p = 0.019 and p = 0.022). Moreover, large tumor size was associated with significantly higher risk of cancer related death at multivariate analysis (p = 0.017), while a trend towards a poorer survival was registered in the high c-MET levels cohort (p = 0.084). Conclusions: In our series, high c-MET expression correlated with poor survival outcomes. Further studies are warranted to validate the clinical relevance and applicability of c-MET as a prognostic factor in ER+/HER2- early BC.Introduction: The mesenchymal-epithelial transition factor (c-MET) receptor is overexpressed in about 14–54% of invasive breast cancers, but its prognostic value in clinical practice is still unclear. Methods: In order to investigate the relationship between c-MET expression levels and prognosis, we retrospectively reviewed the clinical features and outcomes of 105 women with estrogen receptor positive HER2 negative (ER+/HER2-) resected breast cancer. We used the Kaplan Meier method to estimate Disease Free Survival (DFS) and Breast Cancer Specific Survival (BCSS) in the subgroups of patients with high (≥50%) and low (<50%) c-MET expression. Univariate and multivariate Cox proportional regression models were performed to assess the prognostic impact of clinicopathological parameters for DFS an BCSS. Results: High c-MET values significantly correlated with tumor size, high Ki67 and low (<20%) progesterone receptor expression. At a median follow up of 60 months, patients with high c-MET tumor had significantly worse ( Breast cancer (BC) is a widely heterogeneous disease which translates to different clinical approaches and treatment sensitivity . RecentlDysregulation of hepatocyte growth factor/mesenchymal-epithelial transition factor gene (HGF/c-MET) pathway plays a crucial role in human carcinogenesis, tumor progression and resistance to antineoplastic treatments. The activation of the HGF/c-MET axis is responsible for the recruitment of four signalling cascades: mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), Phosphatidylinositol 3-kinase (PI3K/AKT), Nuclear factor-kappa B (NF-κB), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) 3/5. Once activated, these signalling pathways promote cell proliferation, invasion, angiogenesis and epithelial to mesenchymal transition (EMT).c-MET amplification, and c-MET protein or HGF overexpression  accessed on 14 November 2022, with adjusted p-value threshold of 0.05. Pathway databases used for the analysis included KEGG, Reactome and WikiPathways. Enrichment analysis was performed using c-Met [ENSG00000105976] as input gene along with Estrogen Receptor 1 [ENSG00000091831], Estrogen Receptor 2 [ENSG00000140009], Progesterone Receptor [ENSG00000082175] and Erb-B2 Receptor Tyrosine Kinase 2 [ENSG00000141736].Pathway and gene ontology enrichment analysis was performed using online g:Profiler [http://gepia2.cancer-pku.cn/#index) accessed on 11 November 2022, using RNASeq expression datasets from The Cancer Genome Atlas- Breast Cancer (TCGA) and the Genotype-Tissue Expression (GTEx). Overall survival (OS) and Disease-free Survival (DFS) plots were derived using “Survival analysis” module of GEPIA2 with parameters including 95% confidence level, “Media” group cut-off and Hazard Ratio with cohort size for low and high expression of C-Met was 534 and 535, respectively.Clinical significance of c-Met in clinical Breast Cancer patients (TCGA-BRCA) was evaluated using Kaplan–Meier plot analysis. This analysis was performed using GEPIA2  online tool (Human Protein Atlas (HPA) is comprehensive and publicly available database which contains spatial distribution of proteins in human tissues and cells derived using immunohistochemistry and immunocytochemistry, respectively. Protein expression pattern of c-MET was studied using HPA to understand its clinical significance in breast cancer.We enrolled 105 patients with breast cancer, mean age 60 years with a median of 59 and a range of 49–72. Of the 105 patients, 30 were younger than 50 years. Sixty-six patients were T1 and 39 T2-T3, 65 patients had no lymph node metastases and 40 N1-N2, with 46 patients with Stage I, 39 Stage II and 20 Stage III disease, respectively. High-intermediate grade of differentiation was recorded in 83 patients and low grade of differentiation in 22 patients; 45 tumours had low and 60 high proliferation markers, respectively; perineural invasion was absent in 87 tumours and present in the 18 remaining cases. We recorded NST in 90, lobular in 11 and other histo-types in four patients, respectively. Chemotherapy was performed in 60 patients see . Interestingly, no expression of c-Met was recorded in the normal tissue except in four samples, where the expression was low, whereas only in five cancer tissues was c-Met not expressed. Indeed, the c-Met percentage distribution in the studied population largely differs between normal and cancer tissues  the null hypothesis: rows/columns were independent. Indeed, the Fisher exact test reported an odds ratio of 453 . The differences in the expression of low/high c-MET in normal and cancer tissue counterparts were highly statistically significant. The results were also confirmed by the staining percentage levels of c-Met  in normal/cancer tissue, the Chi-square test, Among the 105 patients, 43 (41%) had high c-MET expression in the tumor specimen while amplification of c-MET gene was not detected in any of the cases .p = 0.023), high Ki67 values  and low PR expression status  was observed. Conversely, the majority of stage I BC showed low c-MET expression .A significant correlation between high c-MET and tumors ≥2 cm . No significant correlation with age, nodal involvement, tumor grade and histological subtype was reported , according to international guidelines. Overall, 43% of the study population did not receive adjuvant chemotherapy, two-thirds of whom had low c-MET levels  and BCSS (p = 0.0013)  and 16 (15%) patients, respectively. The c-MET overexpression was significantly related to worse DFS ( 0.0013) .At univariate analysis, a significant higher risk of recurrence or death was registered for patients affected by high Ki67, elevated c-MET and stage III tumors .p = 0.021 and HR: 8.58, 95% CI: 1.95–37.79, p = 0.004).The multivariate regression analysis confirmed tumor stage and c-MET expression as independent prognostic factor for both DFS and BCSS. Specifically, women with stage III tumors or high c-MET expression had three to eight times higher risk of relapse than those affected by early stage (I-II) or low c-MET BC, respectively .Similarly, this subset of patients had also a significant increased risk of cancer death  it is a retrospective study with a limited number of cases; (ii) there is currently no widely accepted standardized methodology for immunohistochemical staining and scoring of c-Met generating bias of data interpretation.Although these data do not allow definitive conclusions, they demonstrate a crucial role of the HGF/c-MET pathway in tumor cell proliferation and clinical behavior and highlight the need for additional investigations on its molecular mechanism in order to promote both the development of anti-MET targeted therapies and the generation of a new prognostic score and decisional algorithm in BC.During recent decades, several efforts have been made to identify specific molecular alterations in order to facilitate the development of novel targeted therapies . In the Overall, despite the small sample size, the lack of a standardized evaluation method and cut-off and the limitations of a retrospective study, our findings suggest the validity of c-MET evaluation for risk stratification process encouraging future clinical trials involving a large population of carefully selected patients to better elucidate its prognostic impact and to evaluate the efficacy of MET inhibitors in luminal subtype .


A decrease in SUV max of more than 60% in the primary tumour was identified as optimal cut-off value for predicting major pathological response and performed better than computed tomography morphologic partial response measured by a size reduction of the primary tumour of more than 30%. The same result was observed for prediction of prognosis.The authors must be congratulated on systematically assessing the role of fluorodeoxyglucose-positron emission tomography and computed tomography in predicting pathological response and prognosis of locally advanced non-small cell lung cancer (NSCLC) after neoadjuvant chemoradiotherapy . IntegraRelevant differences were identified for the subgroup of T3-4N0-1 patients compared to N2 positive patients and a decrease of <60% of SUVmax was found as an indicator of poor prognosis, particularly in N2 patients. The analysis was focused on metabolic and imaging response in the primary tumour, whereas lymph node status was analysed pathologically.Previous analyses of well-designed prospective trials looking at pre-treatment metabolic tumour volume only showed conflicting results on the impact on 5-year survival rates , whereasIn the current treatment landscape, the presented data will be challenged by several issues. Particularly, the details of pathologic reporting after neoadjuvant treatment are crucial to ensure comparability of trials. In 2020, the ‘International Association for the Study of Lung Cancer’ (IASLC) has reported a multidisciplinary recommendation for pathologic assessment of lung cancer resection specimens after neoadjuvant treatment . The autThe integration of immunotherapy in neoadjuvant treatment algorithms  will leaIn summary, innovative neoadjuvant combination schemes have the potential to substantially change staging algorithms in NSCLC. The paper by Tanahashi and colleagues provides relevant confirmatory reference data on the impact of metabolic response on pathologic response rates and 5-year survival rates after neoadjuvant chemoradiation therapy.


Kimura’s disease (KD) is an uncommon lymphoproliferative fibroinflammatory disorder. Patients present with head and neck subcutaneous nodules with or without lymphadenopathy. Peripheral blood eosinophilia and elevated serum immunoglobulin E (IgE) levels are typical. This study was designed to delineate the clinicopathological features, pattern of care, and disease course of 23 Taiwanese patients with KD.We retrospectively analyzed the clinical data of 23 consecutive cases  of KD diagnosed at our institution from 2015 to 2020.The median time from presentation to diagnosis was 1 month. Twenty-one patients presented with unilateral or bilateral head and neck masses. The remaining two presented with right flank and right arm lesions, respectively. Peripheral blood eosinophilia was observed in nine, and elevated IgE levels were observed in four. All were diagnosed using either excisional or core-needle biopsy. Seven patients underwent fine needle aspiration without a diagnostic yield. Salivary gland and lymph node involvement was observed in three and seven patients, respectively. Most lesions showed tissue eosinophilia (100%) and florid follicular hyperplasia (78.26%). Three cases had histological KD-IgG4-RD overlap and three had comorbid IgG4-RD were recognized. Thirteen patients underwent surgical resection, one received adjuvant therapy, and two received prednisolone monotherapy.+ plasma cells is a common feature. Consideration of IgG4-RD in all KD patients may be prudent.KD should be considered in patients with subcutaneous masses, eosinophilia, and elevated IgE levels. Biopsy remains the gold standard of diagnosis. Increased recruitment of IgG4 Kimura’s disease (KD) is an uncommon lymphoproliferative fibroinflammatory disorder which classically affects middle-aged Asian men, with a typical presentation of painless head and neck subcutaneous nodules, regional lymphadenopathy, peripheral blood eosinophilia, and elevated serum immunoglobulin E (IgE) levels. A history of atopy is frequently identified. The disease was first described by Kimm and Szeto in 1937 and better characterized by Kimura et al. in 1948 .+ and IL-5+ mast cells and T cells along with increased infiltration of eotaxin+ and C–C motif ligand 5  + mast cells, T cells, and activated eosinophils  2 cytokines plays a significant role in its pathogenesis, in which tissue injuries, allergies, infections, endocrine disorders, and autoimmunity are potential triggers –7. Studiinophils , confirmThe reactive nature of this disease is reflected in the distinct histopathologic patterns of florid follicular hyperplasia, inter- and intra-follicular dense eosinophilic and lymphoplasmacytic infiltration, eosinophilic micro-abscesses , increased small blood vessels, and prominent stromal fibrosis. Lymphoproliferation is associated with the proliferation of post-capillary venules. However, high endothelial venules are atypical. The replacement of normal germinal centers with IgE or eosinophilic deposits, necrosis, and polykaryocytes (Warthin–Finkeldey-type giant cells) can be present , 10. In Visceral involvement is a rare complication and can present late in the disease course, warranting a long-term follow-up. Renal complications are among the most documented, ranging from urinalysis abnormalities to renal insufficiency. Several pathologies have been associated with KD, including focal and segmental glomerulosclerosis, membranous glomerulonephritis, membranoproliferative glomerulonephritis, eosinophilic tubulointerstitial nephritis, minimal change disease, and acute tubular necrosis –15.To characterize the clinicopathological features, pattern of care, and disease course of KD in Taiwanese patients. Data from 23 affected patients were retrospectively reviewed.In this retrospective single-institution multicenter study, patients diagnosed with KD from 2015 to 2020 at Chang Gung Memorial Hospital (CGMH), a tertiary referral medical institution in Taiwan including two medical centers with four main branches and six subsidiary establishments across the country, were analyzed. Medical charts of all the cases were collected from the time of diagnosis to September 2022. Clinical data before the diagnosis of KD were retrospectively examined to determine the time from initial presentation to disease diagnosis.Kimura’s disease was defined pathologically, after the exclusion of granulomas and evidence of malignancy, with a constellation of tissue eosinophilia and eosinophilic microabscesses, florid follicular hyperplasia with prominent germinal centers, interstitial fibrosis, lymphoplasmacytic infiltrates, increased small blood vessels, and post-capillary venule proliferation.The diagnosis of IgG4-related disease (IgG4-RD) was made according to the 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for IgG4-RD.A detailed review of the medical records of the 23 consecutive cases, including laboratory, imaging, and pathology data, was conducted for the 23 consecutive cases.This study was approved by the Institutional Review Board of Chang Gung Memorial Hospital (202100959B0). There was no need to obtain consent.The clinical characteristics of the 23 cases were listed in Of the 23 cases, 16 were male and seven were female. The age at diagnosis ranged from 12 to 77 years (median: 39 years).Five patients had a history of atopy ; one of whom had concurrent eczema, pompholyx, urticaria, seborrheic dermatitis, and leukocytoclastic vasculitis. One patient had rheumatoid arthritis, one had IgG4-RD with positive anti-nuclear antibody (ANA) , and one had systemic mastocytosis and polycythemia vera  with JAK2V617F mutation and myelofibrosis. Two additional cases of IgG4-RD were recognized during the workup for KD.Of the 23 patients, 21 patients presented with either unilateral (90.48%) or bilateral (9.52%) head and neck masses. The remaining two patients presented with right flank and right arm lesions, respectively. The detailed sites of involvement are shown in The maximal lesion diameter ranged from 0.4 to 4.9 cm.An increased proportion of eosinophils was observed in nine (56.25%) patients, ranging from 5.8% to 41%.Four (100%) patients had elevated IgE levels, ranging from 193 to 4,090 IU/dL .Among the 23 patients who sought care from our institution, eight visited the Otolaryngology Department, five visited the Dermatology Department, three visited the General Surgery Department, and two visited the Pediatric General Surgery Department. The remaining five patients visited the Neurosurgery, General medicine, Ophthalmology, Plastic Surgery, and Infection departments, respectively.All patients were definitively diagnosed with KD using either excisional or core-needle biopsy. Seven patients underwent fine needle aspiration of no diagnostic yield during initial workup. The time from presentation to diagnosis ranged from 1 to 120 months, with a median duration of 1 month.Kimura’s disease was diagnosed by the microscopic identification of characteristic features after exclusion of granulomas and evidence of malignancy. Immunochemical staining was performed for some patients as a confirmatory measure.n = 3), Otolaryngology (n = 2), Plastic Surgery (n = 2), Dermatology (n = 2), Pediatric General Surgery (n = 2), Rheumatology (n = 2), and Neurosurgery (n = 1) departments.Patients received treatment at the General Surgery (n = 4), Rheumatology (n = 4), General Surgery (n = 3), Otolaryngology (n = 3), Plastic Surgery (n = 2), Hematology (n = 2), Pediatric Hematology (n = 2), Neurosurgery (n = 1), Ophthalmology (n = 1), and Infection (n = 1) departments. Mean follow up duration was 68.0 months (21–95 months).Patients received follow-up at the Dermatology  patients. Three (13.04%) patients had lesions involving the salivary glands.n = 23, 100%), florid follicular hyperplasia with prominent germinal centers , interstitial fibrosis , lymphoplasmacytic infiltrates , and increased small blood vessels . Proliferation of post-capillary venules (n = 4), eosinophilic microabscesses (n = 2), and hyalinized vessels (n = 1) were also present  underwent surgical resection. One patient received adjuvant prednisolone therapy with per os [po] prednisolone 10 milligrams [mg]/day for 5 months followed by 15 mg/day for another 7 months. Two patients received prednisolone monotherapy. One of them received oral prednisolone 15 mg/day for 17 months followed by 25 mg/day for 25 months and 20 mg/day for another 28 days. He subsequently lost follow-up. The other one received oral prednisolone 20 mg/day for 31 months followed by 10 mg/day for 36 months. She was still on a maintenance dose of 2.5 mg/day at the end of our study period.Of the 23 patients, 15 (65%) received treatment. Most patients  in a younger population . In our One case  in our series presented with a right flank mass. In contrast to the typical subcutaneous site of involvement, biopsy revealed an unusual dermal distribution of the typical features of KD, including marked tissue eosinophilia with follicular proliferation, spanning the entire dermis extending to the superficial subcutis. The pathologist characterized the lesion as a cutaneous counterpart of KD by the pathologist.Another atypical case  presented with a left malar subcutaneous lesion. The histological features, although more suggestive of KD, were consistent with eosinophilic (lobular) panniculitis. There has been one report on the coexistence of KD and eosinophilic panniculitis in the literature . The sigHistorically, angiolymphoid hyperplasia with eosinophilia (ALHE) was considered a vasculoproliferative counterpart of KD. The entity, typically affecting an older population with a more equal sex ratio, is distinguished histologically by profuse vascular proliferation with plump histiocytoid endothelial cells, scar lymphoproliferation and eosinophilic infiltrates, and cutaneous involvement . Periphe+ plasma cells, storiform fibrosis, obliterative phlebitis, and a mild-to-moderate degree of tissue eosinophilia. Follicular hyperplasia, a prominent feature of KD, has been described in IgG4-RD. Notably, marked tissue eosinophilia does not exclude the diagnosis. Since IgG4-RD is a clinicopathologically defined entity, the associated pathology, although highly consistent across involved organs, is not diagnostic in and of itself. Nevertheless, the constellation of features, as well as a similar tendency to cluster with allergic conditions , render IgG4-RD an important differential diagnosis of KD. Careful clinicoseropathological evaluation is crucial for pertinent diagnosis and optimal management.IgG4-RD is a distinct fibroinflammatory condition often manifested as tumefactive lesions, characteristically featuring a dense lymphoplasmacytic infiltrate with increased IgG4+ plasma cells, to a degree of an IgG4+/IgG+ cell ratio of >40%, was found in the otherwise typical KD lesions of three patients. Of whom two  fulfilled the 2019 ACR/EULAR classification criteria for IgG4-RD  with a titer of 1:1,280.Additionally, we found one case  of recurrent left submandibular mass and lymphadenopathy, who underwent multiple biopsies in 2014, 2015, and 2017. Before 2015, her lesions were consistent with KD without evidence of increased IgG4Kimura’s disease lesions are characterized by a chronic Th2 inflammatory milieu . T cell-Without accounting for the genesis of IgG4, the 2019 ACR/EULAR classification criteria for IgG4-RD are inadept to discriminate between KD and IgG4-RD due to their phenotypic similarities. Another pitfall is the high comorbid rate of atopic conditions, a feature that may prohibit precise determination of the significance of an observed Th2 response in either disease. Moreover, despite the potential difference in the pathogenesis of KD and IgG4-RD, the presence of KD does not preclude IgG4-RD, and vice versa. Hence, the diagnosis and management of apparent KD-IgG4-RD overlap remain challenging. As increased IgG4 secretion is likely an epiphenomenon in both conditions, future investigations comparing the two conditions may shed more light on their respective pathogenesis, as well as the implications of elevated IgG4 in disease manifestation and progression.Since malignancies are known complications of IgG4-RD, our finding of high prevalence of IgG4-RD in patients with KD suggests that workup for IgG4-RD—immunochemical staining of lesion samples along with serological testing for IgG4 levels—is prudent in all patients with or under suspicion of KD. In light of our current understanding of their respective natural history, aggressive corticosteroid therapy with an emphasis on renal function monitoring is likely warranted for the management of these cases of KD-IgG4-RD overlap. Further studies comparing the clinical course and outcomes of KD, KD/IgG4-RD, and IgG4-RD are needed to provide more clinical guidance on patient risk stratification and optimal therapeutics.None of the 23 patients enrolled in this study had documented visceral involvement. This may reflect the rarity of such complications; the detection of which is further limited by the short follow-up duration. Long-term follow-up with urinalysis and guided by clinical clues may be warranted to detect potential late-onset visceral involvement, particularly for those who received local management  alone or no treatment.A treatment algorithm for KD was recently proposed. Patients were stratified according to lesion size, disease duration, and laboratory results. The mainstay treatment consisted of surgical resection. Radiation therapy and immunosuppressive agents are considered add-ons as a part of salvage or adjuvant therapy to prevent recurrence in high-risk patients .Surgical resection was the major treatment modality in our series. The incorporation of prednisolone was deliberated based on the presence of features of IgG4-RD and the degree of eosinophilia.Of the two patients newly diagnosed IgG4-RD, one underwent surgical resection and subsequent prednisolone therapy at the Rheumatology Department, whereas the other patient underwent surgical resection alone at the Otolaryngology Department. As noted previously, further studies on the management of KD versus KD/IgG4-RD phenotypes are of interest.Two patients received prednisolone monotherapy. One presented with antecedent diagnosis of IgG4-RD and the other had marked eosinophilia (41%); both of whom were managed by rheumatologists.Apart from the one case with recurrent left submandibular mass, no short-term treatment complications or recurrence were noted in this series. The relatively short follow-up time precludes the detection of long-term outcomes.Kimura’s disease should be considered in patients with subcutaneous masses, peripheral eosinophilia, and elevated IgE levels with or without a history of atopy. Biopsy remains the gold standard of diagnosis, yielding better results. Increased recruitment of IgG4 + plasma cells, sometimes fulfilling the diagnosis of IgG4-RD, is not an uncommon feature, complicating the diagnosis and management, and possibly warranting workup for IgG4-RD in all patients under the evaluation for KD. As increased IgG4 secretion appears to be an epiphenomenon in both KD and IgG4-RD, the current ACR/EULAR classification criteria for IgG4-RD may not be adept to differentiate the two conditions. Future endeavors in comparing the two conditions may shed more light on their respective pathogenesis and the clinical implications of elevated IgG4. Potential visceral involvement appears to be a largely overlooked aspect of KD in clinical practice. Larger series with longer follow-up time are needed to further demonstrate the prognosis of KD in Taiwanese patients. Particularly of interest are the rates of visceral involvement and recurrence, as well as the comparative clinical course and outcomes of KD, KD/IgG4-RD, and IgG4-RD. Prospective trials are warranted to determine the optimal treatment method for KD.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.This study was reviewed approved by the Institutional Review Board of Chang Gung Memorial Hospital (202100959B0 and 202201725B0).T-MC: conceptualization, methodology, software, validation, formal analysis, investigation, resources, data curation, visualization, project administration, and funding acquisition. C-CL and T-MC: writing—original draft preparation and writing—review and editing. T-MC and K-HY: supervision. All authors read and agreed to the published version of the manuscript.


Steel corrosion is the main cause of reinforced concrete cracking. Conventionally, concrete is considered to crack when the circumferential tensile stress reaches the tensile strength of the concrete. However, few analyses have considered the fracture criteria of the internal cross-section of concrete. Based on the von Mises distribution of angle probabilities, this paper proposes a new probability distribution function for investigating the distribution law of corrosion products. The cracking process of experimental samples was numerically analyzed, and the results were consistent with those of the theoretical model. The effect of the dry–wet cycle ratio on the corrosion products was preliminarily investigated by microscopic observation of the reinforced concrete under different dry–wet cycle corrosion environments. Reinforcement corrosion increases the volume of corrosion products, causing internal pressure in concrete. Internal pressure leads to concrete cracking, structural damage, and economic losses ,2,3,4,5;In a conventional view, the concrete will crack when the circumferential tensile stress reaches the tensile strength of the concrete ,14,15. Tsettings ,18. Zhimsettings  measuredsettings  observedHowever, the aforementioned studies assumed that the materials exhibited linear elastic tensile behaviors, and did not consider the actual characteristics of the materials. Smarzewski  recentlyThe present paper develops a theoretical model of nonuniform corrosion cracking of steel bars. This model is based on a probability distribution function and considers the fracture criteria of the internal cross-section of concrete, which has rarely been considered.The corrosion products include the corrosion products filling the void area, in the corroded part of the reinforcement, and beyond the void area see .In the following, The total amount of corrosion products (mg) is expressed using the following geometric relationship:3), 3), and In the planar problems, the thickness can be taken as one unit, and the corrosion products filling the voids are given by3).According to the geometric relationship in Beyond the void area, the amount of rust products is calculated as:W1—is the filling amount of the rust products extending beyond the void area corresponding to W2—is the filling amount of the rust products extending beyond the void area corresponding to dV is the volume of the corrosion products outside the filling void area (mm3).Substituting Equations (2)–(4) into Equation (1), the total amount of the corrosion products is obtained as:Some scientists have demonstrated that the thickness of the void zone  omitted . Accordin of the corrosion products. Using this ratio, the total volume of the corrosion products (mm3) can be related to the volume versus the reinforcement consumed as follows:The volume ratio of all the corrosion products to the reinforcement consumed is called the expansion ratio The total volume of the corrosion products is the sum of three parts:In the planar problems, the filling volume of the corrosion products can be obtained by calculating the per-unit thickness as follows:Combining Equations (7) and (8), the total volume of the corrosion products is given bySubstituting Equations (9) and (10) into Equation (11) yieldsAfter simplification, the volume 3), and 3).From Equation (13), the corrosion rate is obtained as follows:Zhao et al. and Wong et al. ,26,27 stThe general Gaussian distribution function is given byk is the nonuniformity coefficient, Notably, the Gaussian function of the corrosion thickness given by Equation (15) has the same form as the general Gaussian distribution function given by Equation (16). The von Mises distribution function  models aThe total thickness of the corrosion products is obtained by summing the consumed thickness of the steel reinforcement, the void-area thickness and the thickness outside the void area, as illustrated in Combining Equations (18) and (19), the relationship between Substituting Equation (20) into Equation (19), the total thickness of the corrosion products is given bySimplifying Equation (21), the thickness outside the void area is calculated as:In the planar problems, the volume of the corrosion products outside the filling void area When the thickness loss of the steel bars is sufficiently smaller than the diameter of the steel bars, In Equation (24), the integral term From Equations (9) and (11), the following equation is obtained:When substituting Equation (25) into Equation (26), the total volume of the corrosion products From Equation (27), the correction coefficient Substituting Equation (28) into Equation (17), the total thickness of the corrosion products is calculated as:From Equation (14), the reinforcement corrosion rate is given bySubstituting Equation (30) into Equation (29) yields the following relationship between the total thickness of the corrosion products and the corrosion rate of the steel bars:When substituting Equation (31) into Equation (22), the thickness outside the void area From Equation (32), the maximum filling thickness of the corrosion products is given as:q = q0sinθ, where π/2. Additionally, as the boundary stress changes with A and B are the coefficients determined by the boundary conditions and constraints.The thickness distribution of the rust layer is assumed to be a semi-ellipse along the upper half-circle, which can be approximately represented using a sine function see . As the R is the radius of the steel bars (mm), and l is the maximum radius of the ring (mm).In the elastic mechanics theory, the stress component can be represented by the radial normal, circumferential normal, and shear stresses in the plane, respectively, given byA and B are obtained as follows:When substituting the boundary condition into Equation (35), the coefficients From Equations (35) and (36), the hoop stress at When the maximum tensile stress at the interface of the reinforced concrete When substituting Equation (38) into Equation (37), the maximum rust expansion force is given byA and B at the critical cracking state are obtained as:By substituting Equation (39) into Equation (36), the coefficients The radial strain is obtained using the following physical equation:The radial strain is related to the radial displacement by the geometric equationWhen substituting Equation (41) into Equation (42), the radial displacement is given as:Finally, when substituting Equation (40) into Equation (43), the maximum radial displacement of concrete at the critical state of interface cracking  and (44), the limit state equation of concrete cracking is expressed as:In the limit state equation proposed in rmaxR = u and d(θ)S = u, the performance function of concrete cracking described using Equation (45) is newly defined asSetting R and S, respectively (in mm).If different nonuniformity coefficients have different effects on corrosion cracking, the corresponding reliability index can be expressed as follows:fc, cover thickness c, reinforcement diameter d, and corrosion rate ρ in the existing data [The averages and standard deviations of the concrete compressive strength ing data  are provβ for the different nonuniformity coefficients was calculated using the aforementioned formulas, and the results are plotted in K, the smaller the β. This trend is reasonable because K represents the filling degree of the rust products around the reinforcement; therefore, as K increases, the rust products become more concentrated. When 0 ≤ K ≤ 1, the rate of the reliability index was at the maximum, indicating a clear influence of the nonuniformity coefficient on the reliability index during the filling process. When K exceeded 1, the influence of the nonuniformity coefficient on the reliability index was reduced.From the statistical data in the relevant literature ,32,33, tTo improve the accuracy of the experimental results, no active agent, except the sodium chloride solution, was added when pouring the concrete. After trial-and-error and adjustments of the mix proportion following the relevant methods specified by the Regulation of Common Concrete Mix Design (JGJ55-2011), the final concrete mix for the test was determined see .After 28 days of moist curing, the specimens were exposed to an artificial environment to accelerate the steel corrosion. The artificial environment was introduced in two stages: corrosion initiation and corrosion propagation. Corrosion initiation involved exposing the specimens to a cyclic dry–wet environment for 1–3 months. Each dry–wet cycle included wetting in a 7% (by mass) NaCl solution and oven-drying at 65 °C . To ensure a similar amount of chloride around the surface of each cross-section, each specimen was placed vertically in a container. The details of the sample groups are provided in The cracking process of concrete through dry–wet cycling is a long-term process, requiring over 1–3 months. The cracking times of the samples are listed in Influence of the thickness of the concrete cover on the cracking timeIn the specimens with the same reinforcement diameter and concrete strength, the cracking time of the specimens increased with the increasing thickness of the concrete cover . As the Influence of the reinforcement diameter on the cracking timeAs illustrated in Effect of the ratio of dry–wet cycles on the cracking timeAs illustrated in The specimens were observed using optical microscopy (OM), environmental scanning electron microscopy (SEM), energy-dispersive spectrometry, and X-ray diffraction (XRD). SEM only observes the surface morphology of the rust layer and cannot depict the true color of the material. Therefore, the sections of reinforced concrete were observed using both the environmental SEM and OM. For convenience, we inserted the test block along the crack with a slotted screwdriver and then pried the test block to remove the inner rust layer. To avoid further oxidation in the air, the test block was quickly transferred to the X-ray diffractometer for observation.The distributions of the corrosion products in the cracks and interfaces were observed and analyzed using OM. The development mode of the rust pits on the reinforcement surface in the dry–wet cycle environment, inferred from the aforementioned analysis, is illustrated in The energy spectrum in As shown in The XRD patterns of eight samples in this experiment were compared with the standard XRD pattern of iron oxide. The results are displayed in The peaks attributable to the corrosion products appeared at the same positions in the diffraction patterns of each specimen, and the strongest peak appeared at approximately The reinforcement in concrete actually corrodes via an electrochemical process ,37,38,39Corrosion proceeds in four basic stages , as depi2O3, and Fe3O4. Among these products, γ-FeO(OH) is a transitional hydroxyl iron oxide that assists the formation of the most stable hydroxyl iron oxide, α-FeO(OH). When concrete exists in a long-term immersion state, its oxygen supply is limited. On the contrary, when the concrete dries over a long period of time, its interior is relatively dry and the oxygen supply is abundant. During the dry–wet cycles in the present experiment, the internal pores were never completely dry or wet; thus, the comprehensive ability of the oxygen supply and diffusion was better than that of those of the fully dry and fully moist states.From the XRD pattern, the major corrosion products in each specimen were discerned as α-FeO(OH), β-FeO(OH), γ-FeO(OH), FeWhen the rust expansion cracks penetrate the concrete cover, the steel bars inside the concrete become oxygen-enriched. In such an oxygen-enriched environment, the rebars produce more high-valence corrosion products, such as γ-FeO(OH) during the dry–wet cycle see .On the basis of the composition and contents of the eight samples and the transformation process of the iron oxidation products, it was concluded that when the dry-to-wet ratio was reduced, the γ-FeO(OH) and β-FeO(OH) contents increased and the α-FeO(OH) content decreased. When the other conditions were identical, reducing the dry-to-wet ratio lengthened the corrosion cracking time and facilitated the formation of β-FeO(OH) and its intermediate product γ-FeO(OH) through the large impact of chloride ions.The main conclusions of this paper are summarized as follows:(1) A theoretical model of nonuniform corrosion cracking of steel bars was proposed. In this model, when the maximum filling thickness of the corrosion products exceeds the radial displacement of concrete, the concrete cracks.K ≤ 1.(2) An analysis of the relationship between the nonuniformity coefficient and reliability index demonstrated that the larger the nonuniformity coefficient, the smaller the reliability index. The reliability index decreased most rapidly in the range of 0 ≤ (3) The development mode of the rust pits on the surfaces of the steel bars did not depend on the wet–dry cycling environment of the concrete.(4) The Fe and O distributions in the energy spectrum of the corroded reinforced concrete were divisible into five areas: reinforcement, rust layer, oxide skin, polluted concrete, and unpolluted concrete.2O3, and Fe3O4. The further comparative analysis indicated that a reduction in the dry–wet ratio of the dry–wet cycles increased the γ-FeO(OH) and β-FeO(OH) contents.(5) Based on the corrosion principle of reinforced concrete and the XRD results, the main corrosion products that were under the different dry and wet cycles were α-FeO(OH), β-FeO(OH), γ-FeO(OH), Fe


Home Hospital (HH) is a unique and rapidly expanding care model that allows patients to receive medical therapy and monitoring through telehealth communication and nursing visits, and there are currently no published studies evaluating antimicrobial stewardship interventions in the HH setting. The goal of this study is to evaluate the impact of a pharmacist-driven antimicrobial stewardship pilot for the HH program.This was a pre-post quasi-experimental study of adult patients enrolled in HH program between January through March in 2021 (control cohort) and in 2022 (intervention cohort), who received antibiotics  during their HH admission. Patients on long-term prophylactic antimicrobials, antifungals, external antimicrobials, or mycobacterial treatment were excluded. The antimicrobial stewardship pharmacist performed prospective audit and feedback and provided recommendations to clinicians through the electronic medical record. The primary endpoint was antibiotic use (days of therapy per 1000 patient-days). Secondary endpoints included broad-spectrum antibiotic usage; appropriateness of antibiotic indication, dosing, and duration; compliance with the institution’s outpatient antibiotic reference guide or outpatient intravenous antibiotic therapy (OPAT) monitoring; treatment failure; antibiotic-associated adverse effects; and cost of antibiotic therapy.The study included 73 and 127 patients in the control and intervention group, respectively . On average, the pharmacist reviewed 8 eligible patients/day. Interventions were generally well received by HH providers . There was no significant difference in the primary outcome. More inappropriate antibiotic indication was identified in the intervention group , associated with post-surgical infection prophylaxis after orthopedic procedures . Other secondary outcomes did not vary significantly between the groups.The pilot allows for better understanding of outpatient and HH antibiotic prescribing practices to provide targeted interventions, and suggests the need for additional antimicrobial stewardship involvement to optimize antibiotic therapy in this novel care setting.Elizabeth B. Hirsch, PharmD, FCCP, FIDSA, Melinta: Advisor/Consultant|MeMed: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support.


We find that respondents are 13% more likely to respond “Yes” and spend 2.1 min less in the binary setting. Additionally, the results suggest that the type of question matters.This paper conducts a pre-registered study aimed to compare binary and continuous set of responses in survey questionnaires. Binary responses consist of two possible opposing response options (Yes/No). Continuous responses are numerical, where respondents can indicate an option on a 0–10 horizontal blind line. We study whether feasible sets of binary and continuous responses yield the same outcome (distribution) and have the same cost (duration in minutes). We collect data from 360 households in Honduras that were randomly assigned to Yes/No questions or given a slider  to mark their responses, therefore, we provide  Agree-disagree scales are used to obtain the degree of agreement with an issue6. However, item-specific questions  are recommended when the scale options in the questionnaire refer directly to the issue under evaluation8. On the other hand, perception questions are used when the interviewer’s goal is to obtain information on how respondents perceive certain issues. This type of question can be less problematic when the response reveals personal information9. Perception questions may induce social desirability bias and can present a reliability problem with open questions, as the wording used might have a different meaning for respondents10. In this case, the use of closed-ended questions and also to know the realities that respondents have to report are recommended11.The literature on survey design, and more specifically the choice of response format, offers a wide typology of questions to evaluate the degree of agreement with an issue12 and they are easy for the respondents to understand. They also involve low costs and less time for both researchers and respondents13. In addition, it has been shown that people correctly answer factual questions (content-specific questions that require only one correct answer) more often when the correct answer is “Yes”3. This format also requires less interpretative efforts compared to longer questions12, although the lack of neutral response may alter the results. For example, it may lead to acquiescence bias, which refers to a respondent’s tendency to agree with a statement without considering the content of the item or to please the researcher16. Moreover, this format could be problematic for respondents with neutral attitudes due to the lack of accurate mapping between moderate responses and the dichotomous options offered. As a result, such a format would require a major cognitive effort18.In social sciences, one of the most widely used types of closed questions is dichotomous scales (binary responses) in which two opposing responses are provided . This typology is generally used when the goal is to evaluate the direction of the answer (agreeing or disagreeing with an issue). There is considerable consensus on the meanings of the options19. Nevertheless, point meanings may become less clear as the respondent cannot differentiate between one number and another12.Continuous rating scales enable researchers to obtain the exact degree of agreement with an issue. When continuous rating scales are numerical, respondents can indicate an option on a horizontal line by marking precise numbers that express the degree of agreement with an issue with respect to a maximum number, usually 10 or 100. The use of this metric scale allows subjects to easily transform their opinions, whether extreme or mild, into replies, thus reducing distortion20. Regarding response time and complexity, continuous scales require more time to explain the set of possible answers and to think about their conversion into numbers, which implies higher reasoning costs19. However, compared to binary responses, a continuous set of feasible answers provides better quality of information12. In binary scales, where respondents have to convert mild responses into Yes–No answers, respondents are forced to make computations to transform their opinion in the middle to an extreme answer, resulting in an inaccurate choice, which consequently may manifest a higher degree of agreement that would not be reached if middle responses were available . Moreover, binary scales do not allow for nuanced responses or permit studying respondents’ expectations at the individual level. Therefore, if respondents have problems computing their mild thoughts into extreme responses, biases arise.When choosing between binary and continuous rating scales, it is important to evaluate the advantages and disadvantages of each type of question. In terms of statistical evaluations, continuous scales allow for a wider range of proceduresThis study investigates the extent to which the use of binary and continuous scales yields different results. Specifically, we examine if the probability of agreeing with a statement is the same when binary and continuous sets of responses are used and subjects have strong opinions regarding the content of the survey, in our case: sexual and reproductive health see “”. To do 22, and increase the time and effort needed to provide an answer18. Sliders also allow respondents to communicate exact values and simultaneously convey to the respondent how precise the expected answer should be23. However, the use of sliders to collect responses can be time-consuming19. In addition to longer completion times, there are other challenges, such as how to handle the starting position of the marker24, or the inclusion or not of anchors and labels25. To overcome these difficulties, we used partially labeled sliders with a scale range of 0-to-10 points that only indicate the extreme points (0 and 10). Additionally, the experiment was conducted by enumerators who read out and explained the instructions to participants. For the continuous questions, they were also in charge of explaining their correct use to the respondents and avoiding issues with incomplete data or with the slider bar movement and interpretation24, therefore, removing all the above-mentioned difficulties.How continuous answers are captured is also important. In this study, we use sliders, a visual analog scale that allows respondents to mark their responses in an interval of 0–10. Sliders are more engaging than other visual scalesTo compare responses between treatments, we discretize the continuous answers. We assign the binary option “No” if the selected response is below 5. Respondents who indicate agreement of more than 5 points are assigned to the binary option “Yes”. When the indicated option is 5, the answer is randomly assigned to “Yes” or “No”. Additionally, we study whether the wording of the questions, such as the use of negative words  or prescriptive expressions  also affects the probability of agreement. We also analyze the differences in terms of the response time for both treatments.15. Negatively worded questions are usually included in surveys to avoid fatigue throughout the questionnaire, acquiescence27 and to prevent respondents from choosing the same answer28. Nevertheless, one of the issues that arises with negative questions is the additional processing effort they require, particularly in binary sets, where respondents have to decide to agree or disagree with a question that includes negation, which may generate confusion30 . In the same line, our data show that when negative wording is used in the questions, the probability of agreement jumps to 37% in binary sets compared to continuous ones.We find that respondents are more likely to respond “Yes” in the binary setting compared to the continuous setting. In particular, the probability of responding “Yes” is 2.3 times higher for the binary than the continuous questions. Regarding response time, binary questionnaires took 2.1 min less, which implies an average reduction of 42.5% with respect to the continuous questionnaires. Our results hold when excluding males from the sample and subjects with lower cognitive abilities. Given the content of the questionnaire we extend the analysis to the wording of the questions. The literature has shown that question-wording also plays an important role in obtaining accurate responses. Negatively worded questions have been defined as those in which disagreement would be a good answerIn certain contexts, asking people to reveal their opinion is challenging. For instance, voters might have concerns about revealing their (private) vote in pre-election polls. Similarly, citizens might also have concerns about sharing private information with the government when they are likely to be assigned to a public program. In both cases, participants might consider that their responses matter and therefore they might feel obliged to complete the survey consciously. To check whether there are differences between binary and continuous sets of questions, we select a topic on which subjects have very strong opinions: sexual and reproductive health.32. In fact, according to33, a Honduran adolescent who is completely “illiterate” about sexual and reproductive health is 44% more likely to become pregnant than a fully informed adolescent. Given the general sensitivity surrounding this topic particularly in this region, we decided that this sample would be ideal to test the impact of the question setting on responses. Considering that the onset of menarche occurs between the age of 9 and 16 years, the eligibility criterion to be part of the sample was having a child between 6 and 9 years old. This was motivated by the fact that children need to have access to information about the menstrual cycle and sexual and reproductive health before menarche, which is an essential part of menstrual health34. The experiment was conducted by a consultancy firm (PILARH) in four districts in which 360 households were randomly selected. Following local procedures, PILARH contacted the territorial Office of the Education Secretary which permitted us access to eleven schools representing different socioeconomic levels. The selected schools were: Divina Providencia, Jerónimo J. Reina, Jesús Banegas Membreño, Jorge Portillo, José Cecilio del Valle, José María Medina, Los Ángeles, Manuel Bonilla, San Antonio, San José and Santo Domingo Savio. School representatives talked to parents and asked them to participate in the study. Only one adult per household was asked to voluntarily complete the questionnaire. The entire experiment consisted of four experimental tasks and a questionnaire, which was completed following the tasks. This study is entirely based on the questionnaire.In May 2019, we ran the experiment in Santa Rosa de Copán (Honduras); an area characterized by high rates of teenage mothers, with a rate of 28.17% of teen pregnancy (mothers of 9–19 years old)The experiment was conducted by twelve enumerators. They were specifically trained for the field work and were in charge of reading and explaining the instructions to the participants. Each of the enumerators received a list of households to visit, which were randomly allocated to the treatments before the visit. The enumerators had no influence on the selection of households to ensure that none of them conducted all the questionnaires for households belonging to the same school. All the interviews were conducted face-to-face in the participants’ households. The questionnaire was paper-based and included 30 questions divided into 6 blocks (A–F) of 5 items each about menstruation and reproductive rights. The original questionnaire in Spanish and its translated version in English can be found in sections https://aspredicted.org/ps766.pdf.This study was approved by the Ethics Committee of Universidad Loyola Andalucía and was conducted according to the principles expressed in the Declaration of Helsinki. All participants signed informed consent before participating. The field study was pre-registered on April 15, 2019 and made public on April 25, 2019 at “Yes” or “No” . This information was provided to the respondents by the enumerators. In contrast, the continuous set of responses allowed subjects to indicate an option within a given interval. Specifically, the enumerators captured respondents’ answers using partially labeled sliders on a scale of 0–10 points that only indicated the extreme points (0 and 10). In this case, enumerators told the respondents to use the slider for each question  were presented. Specifically, 52% of the participants started with blocks A, B, and C  while the remaining 48% started with blocks D, E, and F, and then completed blocks A, B, and C. The order of the items within each block remained the same.To assess the effect of binary versus continuous sets of responses in a questionnaire, subjects were randomly allocated to The enumerators received instructions about the treatment and the order of the questions to be used for each household.35 developed by36. This test consisted of several questions that allowed us to determine whether the respondents were able to deal with probabilities  each participant took to complete the entire questionnaire . Finally, to account for respondents’ ability, we used an extension ofThe total sample consisted of 360 subjects. However, seven of them did not answer all the questions, resulting in a response rate of 98%. Supplementary Table All the subjects completed the same questionnaire with only one difference, the type of answer (binary vs continuous). Of the participants, 52% answered binary questions (Yes/No), and 48% answered continuous questions.Finally, we provide the balance of the randomization across treatments in our experiment  or continuous form , the responses to the two types of questionnaires (binary and continuous) need to be comparable. Following the existing literature38, we discretize the continuous responses and then compare them with the binary responses. Note that respondents have no information on the codification of their answers.To determine whether individuals respond differently to the same question depending on whether it is asked in binary form  responses greater than 5 indicate agreement with the survey question; (2) responses less than 5 indicate disagreement with the survey question; and (3) responses equal to 5 indicate neither agree nor disagree. Then, as a result, when the response is 5, we randomly assign the individual to “Yes” or “No”.We opted to split answers equal to 5 as this value represents the mean point in the continuous set. Using the slider, we can measure the intensity of an opinion. Similarly to our case, the well-known Likert scale questionsA, and 48% starting from block E). Figure “Yes” responses, along with the average time (in minutes) respondents spent on the entire questionnaire in both continuous and binary forms.We start by showing the results of the participants’ behavior along with the entire experiment. Recall that all participants replied to 30 questions in random order  and repeat the same exercise to check whether the results are driven by the very few men in the sample (13%). Second, we remove subjects facing problems with probabilities  and complete the survey much faster. These results are robust to excluding men and low-ability respondents. Supplementary Table In conclusion, the use of binary (instead of continuous) sets of responses causes subjects to respond “Yes” (and “No”) responses to each question. As can be seen, Result 1 (higher number of “Yes” responses to binary questions) does not hold for every single question. Indeed, we see that many items are almost identical in the binary or continuous setting. In particular, we find that 10 out of 30 questions are different and, most importantly, the direction of the difference is always the same  as in Result 1.Supplementary Fig. Figure For sake of completeness we repeat the analysis for women only and for the sub-sample of subjects who passed the cognitive test. Results remain in the same direction : negative, prescriptive, and other. Similar to the previous literature, Prescriptive refers to those questions that include wording like “have to” or “must be”, or refer to what one should do, what is right or wrong, or good or bad41. Other questions refer to questions that cannot be classified as either negative or prescriptive. SQ5 in Panel A; SQ5 in Panel B; SQ5 in Panel C; SQ1, SQ4 and SQ5 in Panel D; SQ5 in Panel E, and SQ5 in Panel F are negative questions. SQ2 to SQ4 in Panel B are prescriptive questions.First, we analyze differences at the aggregate level in the binary and continuous settings for each group of questions . That is, we compare the total number of “Yes” responses in binary and continuous forms. We start with the whole sample. Table Result 4:The probability of agreeing with the survey question is higher when a binary set of responses and negative wording are used (36.8%).We repeat our analysis for women and removing subjects with low-ability according to the results obtained from35 .Our first result shows that, on average, the probability of agreement is 13% higher in binary sets compared to continuous sets. The fact that the binary setting yields higher agreement rates is not new. Indeed, this type of survey question is affected by acquiescence, that is, the tendency to agree with the question without considering the content of the item  and, as expected, Result 2 shows that continuous settings require more time than binary settings. Specifically, opting for Yes-No responses reduced the average length of the survey by 2.1 min, which implies a reduction of 42%. This result is also expected given the wider range of options offered to the respondents, who may need more time to accurately map their opinion in an interval of 0–10.To check whether Results 1 and 2 are robust, we analyze the probability of agreement focusing on two particular sub-samples: women and respondents’ ability. When we consider only women in the sample, which account for 87% of the sample, we find similar results: the probability of agreement is 2.25 times higher in the binary than in the continuous sets. The length of the questionnaire is also 1.9 min shorter when using binary questions for this sub-sample. Hence, the differences in the probability of agreement and time to complete the questionnaire between binary and continuous sets of responses are not driven by men.35 . We find that 71% of the sample responded correctly to these questions. Using this sub-sample, we test our data and find similar results: high-ability respondents require on average 2.49 min less when using a binary rather than a continuous questionnaire, which implies a reduction of 48%. We also find that the probability of agreement is higher in binary sets compared to continuous sets. Specifically, respondents answer “Yes” 2.5 times more (or 14.4%) in binary sets16.Additionally, we consider respondents’ ability using an extension ofThird, we also estimate the differences in the responses for each question. Result 3 shows that 33% of all questions present significant differences between the binary and the continuous sets, with a higher agreement in the binary setting in all cases. These results hold when we only consider women and when we take the high-ability sub-sample of respondents.negatively worded questions, that include negative adverbs in the sentence. Specifically, 8 out of 30 questions include negative words, of which 7 show significant differences when we compare the binary and the continuous treatment. This specific group of questions shows 37% more agreement in the binary than in the continuous sets. The group of questions classified as “other” also shows 9.5% more agreement in the binary than in the continuous sets. However, the group of questions with prescriptive words shows no differences. The use of negatively worded questions is recommended to avoid acquiescence and inattention. However, we obtain the opposite result. Therefore, we advise the survey researcher to use negatively worded questions with caution as its use might cause reliability and validity problems, overall in binary sets and with individuals with lower general education .To go a step further, we analyze whether the wording of the questions matters. In particular, we distinguish between 42.Although the results indicate that binary questions can be responded more quickly and are thus more efficient in terms of time and cost, one of the limitations of this research is that we do not know the true answers: the information we obtained from the questionnaire does not allow us to assess whether binary or continuous settings reflect true answers44 as respondents may have problems in disentangling perception versus preferences. An interesting line of further research would be to compare both settings when the social norm is clearly defined.In short, in the absence of true values we cannot prove which setting is more accurate. Furthermore, it is also important to remark that the sensitivity of the topic and the use of perception questions to avoid possible situations of social desirability bias might have an impact on subjects’ responsesWhile our results are remarkable, it should also be noted that our study has two major limitations that preclude us from generalizing the results. First, our sample is very specific: inhabitants of semi-rural areas of Honduras (mostly women). Second, the topic—sexual and reproductive health—is fairly sensitive. Further research with a more general population and less sensitive questions would be necessary.This paper aimed to test whether using binary or continuous sets of questions leads to different responses. To this end, we designed a quasi-experimental survey where subjects were randomly assigned to the binary or continuous treatment, hence we have provided causal evidence. The experiment was conducted in Honduras with 360 randomly selected participants. At the aggregate level, we found that subjects are more likely to respond “Yes” in the binary setting (Result 1). We also found that subjects in the binary treatment spent 42% less time responding to the entire questionnaire (Result 2). Thus, using a continuous set of responses comes at a higher cost. We also tested whether both results still hold when the sample is composed only of women (87% of the sample) and the results are similar. We also tested whether the results remain constant when controlling for cognitive abilities. The proportion of subjects classified as having low-ability is 29%. The results obtained when removing this subgroup of participants are similar to those using the whole sample. We then estimated the difference between the binary and the continuous treatment question by question and found two relevant results. First, the differences between binary and continuous sets do not occur in every single question but only in 33% of them. However, the difference between a binary and continuous sets always goes in the same direction. That is, the probability of agreeing with the survey question is higher when using a binary instead of a continuous set of responses. Finally, we analyzed the role of question-wording. To that end, we differentiated between questions with negative, prescriptive, and other wording. We found that negative wording increases the probability of subjects responding “Yes” by 37%. No differences were found between binary and continuous questions when using prescriptive wording; in sum, our paper provides causal evidence of the difference between binary and continuous set of responses. We found that the type of answer is important and could yield different results. In addition, how the question is worded could play an important role in explaining its results.Supplementary Information.


Randomised trials provide high-quality evidence on the effects of prescribing antibiotics for urinary tract infection (UTI) but may not reflect the effects in those who consume antibiotics. Moreover, they mostly compare different antibiotic types or regimens but rarely include a ‘no antibiotic’ group.To estimate the effect of antibiotic consumption, rather than prescription, on time to recovery in females with uncomplicated UTI.Secondary analysis of 14-day observational data from a point-of-care test trial for UTI in primary care in England, the Netherlands, Spain, and Wales, which ran from 2012 to 2014. Clinicians treated patients using their own judgement, providing immediate, delayed, or no antibiotic.UTI-symptomatic females who either consumed or did not consume antibiotics during a 14-day follow-up were included. Antibiotic consumption was standardised across participants and grouped into either ≤3 or >3 standardised antibiotic days. To account for confounders, a robust propensity score matching analysis was conducted. Adjusted Kaplan–Meier and Cox proportional hazard models were employed to estimate time to recovery and hazard ratios, respectively.n = 333 females who consumed antibiotics and n = 80 females who did not consume antibiotics were identified and included in the study. The adjusted median time to recovery was 2 days longer among patients who did not consume antibiotics  compared with those who did . No difference was found between those who consumed ≤3  compared with >3 standardised antibiotic days .A total of Consuming antibiotics was associated with a reduction in self-reported time to recovery, but more antibiotics exposure was not associated with faster recovery in this study. Non-pregnant, adult female participants who had at least one of the main uncomplicated UTI symptoms — dysuria, frequency, or urgency — were recruited during routine consultation. Patients with pyelonephritis, other severe systemic symptoms, or who received antibiotics 4 weeks before recruitment, were on long-term antibiotics, or had genitourinary tract abnormalities were not recruited.15 Clinicians treated patients  using their own judgement or with the aid of the Flexicult™, which provided results on pathogen and antibiotic strength, mg × total number of consumed doses published defined daily dose (DDD)19 antibiotics sensitivity 24 hours after recruitment, and, if necessary, treatment was changed accordingly.15Data from the Point of care testing for urinary tract infection in primary care (POETIC) trial were analysed.urgency;burning or pain when passing urine (dysuria);daytime frequency;night-time frequency;smelly urine;pain in the side;abdominal pain;fever;blood in urine;restricted activity; andgeneral unwell feeling on a scale of 0 to 6 (0 = ‘not affected’ and 6 = ‘as bad as can be’).Clinicians completed a baseline questionnaire detailing the severity of symptoms, history of previous UTI treatments, and management chosen. Patients then completed a 14-day diary in which they rated the severity of 11 symptoms:Daily consumption of medication and day of recovery (patient answered a direct question on when they have felt completely recovered) were also documented.Data from patients who were either prescribed an antibiotic immediately, or not at all, were included. Patients with delayed or changed antibiotic because of resistant infection were excluded to create a clear definition of both exposure and outcome. Patients with missing data for the type, strength, and dose of antibiotic used were excluded.17–19 Consumption ranged from 0.17 to 14 standardised antibiotic days and patients who consumed antibiotics were categorised into two categories: ≤3 and >3 standardised antibiotic days:Patients were categorised into two groups: whether they consumed any antibiotic during follow-up or not. A standardised antibiotic consumption unit (standardised antibiotic days) was implemented to allow comparison between different antibiotic strengths and dosing regimens.20 and Cox proportional hazard models double robust method21,22 were used to compare median time with recovery and hazard ratio (HR), respectively, between patients who consumed antibiotics and those who did not, and between those who consumed >3 and ≤3 standardised antibiotic days.Kaplan–Meier survival analysisPropensity score matching models were used to adjust for confounding factors including the severity scores for baseline symptoms (listed above), analgesic use , antifungal use , antimuscarinic use , age, and country. For the analyses where standardised antibiotic days were compared, day-3 symptom scores were added as confounding factors, as this might have also affected patients’ decisions to continue taking their antibiotics and it did improve the propensity score balance between the groups (data not shown).23 yielded a good balance using the R package ‘MatchIT’.24 In this method, propensity score was estimated using a logistic regression of the antibiotic consumption on the confounding factors listed above. The researchers used all observations from groups and no units were discarded during matching.Among many attempted propensity score matching methods, marginal mean weighting through stratificationSensitivity analysis was conducted to include UTI treatment history in the calculation of the propensity score. Data analysis was conducted in R (version 4.0.5).N = 413 (64.2%) patients after exclusion of patients with missing follow-up data , changed antibiotics , delayed antibiotics , and missing data required to calculate the standardised antibiotic consumption   .n = 80 (19.4%) patients consumed no antibiotics, of whom n = 75 were not prescribed antibiotics and n = 5 were prescribed antibiotics but did not consume any. Among those who consumed antibiotics , nine antibiotics were used: trimethoprim , nitrofurantoin , fosfomycin , ciprofloxacin , norfloxacin , amoxicillin clavulanic , amoxicillin , cephalexin , and cefuroxime . Among those who consumed ≤3 standardised antibiotic days (n = 201), n = 181 (90.0%) patients were prescribed a course of 1 to 3 days, n = 17 (8.5%) patients were prescribed a 5- or 7-day course, and n = 3 (1.5%) patients had missing data for prescription duration. Among those who consumed >3 standardised antibiotic days (n = 132), there were n = 11 (8.3%) patients with 1 to 3-day prescription and n = 121 (91.7%) with 4 to 8 or a 10-day prescription.Of the final cohort, The mean age of patients was 48.4  years for the entire cohort, and similarly distributed across the antibiotic consumption groups . PatientAt baseline, mean symptom severity scores were generally slightly higher among those who consumed antibiotics compared to those who did not , but theUTI treatment within the past year was received by 181/274 (66.1%) and 39/55 (70.9%) patients among those who did and did not consume antibiotics, respectively . There wOnly small proportions of the study cohort consumed over-the-counter analgesics, antifungals, and antimuscarinics at some point in the follow-up. However, there was a lower proportion of females taking antifungals (1.8% versus 2.5%), antimuscarinics (0.9% versus 1.3%), or analgesics (4.5% versus 10.0%) among those who consumed antibiotics compared with those who did not. These proportions were similar across the standardised antibiotic days groups .UTI microbiological culture results were known to clinicians after the initial management decision was made, thus it was not included as a confounder. However, the researchers have summarised its proportions among antibiotic consumption groups in n = 331 (80.1%), reported complete symptom recovery during the follow-up. Only two (0.5%) reported not having recovered by day 14, but n = 80 (19.4%) had missing recovery data, therefore their recovery time was censored. Among those who consumed no antibiotics, n = 50 (62.5%) patients reported recovery during the follow-up, while n = 281 (84.4%) reported recovery among those who consumed antibiotics.Most participants, P<0.001)  days. Following adequate propensity score balancing , the adjP<0.001) . Those wP<0.001) .P = 0.026) (P = 0.086), nor a significant HR  for those who consumed >3 compared to those who consumed ≤3 standardised antibiotic days (The adjusted median time to recovery among those who consumed ≤3 and >3 standardised antibiotic days was similar (7 days for both) with a wider 95% CI among the latter (95% CI = 6 to 9) compared with the former group  . This antic days .n = 220) or not (n = 109) were included in a sensitivity analysis where this important confounding factor was adjusted for. Both the estimated median time to recovery  compared with not taking antibiotics, after matching by baseline characteristics and use of other medication. However, when considering history of UTI treatment as a confounder, recovery could be as much as 7 days longer in those who consumed no antibiotics. No substantial difference was found in time to recovery among those who consumed more antibiotics, which was supported by the Cox model HR and target trial analysis.25,26 which weakens conclusions from prescription data. To the authors’ knowledge, only one other study12 explicitly explored recovery from UTI using antibiotic consumption rather than prescription data. The present study included most of the antibiotics used to treat uncomplicated UTI, and variable antibiotic exposure  was standardised by calculating a standardised antibiotic consumption. A further strength of this study is the use of propensity score matching based on the initial symptoms to estimate effects on time to recovery. This approach helps correct for indication bias, where those with more severe symptoms are more likely to be prescribed and consume antibiotics. Further, sensitivity analyses using UTI treatment history as a potential confounder were conducted. UTI history is an important factor that affects clinicians’ decisions to prescribe and patients’ decisions to consume antibiotics. However, this information was missing from 84 patients, hence the use of sensitivity analysis. The results highlighted the importance of this confounder and suggest that it should be included in future studies.Non-adherence is a recognised issue in community infection management,15 However, the POETIC study did not include patients with UTI symptoms lasting >2 weeks. Moreover, the authors recognise that the 2 days longer time to recovery among those who consumed no antibiotic might be so if longer follow-up was considered; however, the survival analysis median time to recovery as opposed to the mean would not be affected by extremely longer recovery durations. The POETIC trial included a follow-up at 3 months on UTI recurrence, but this was not considered for this study as the researchers were interested in the immediate recovery from uncomplicated UTI infection. Though antimuscarinic, antifungal, and analgesic use was adjusted for, binary indicators were used and did not consider the amount, duration, or time point these were consumed, as this information was not collected. Data from a randomised trial of a point-of-care test were used that could potentially affect antibiotic prescribing. However, the test results were not available to clinicians until approximately 24 hours after the initial consultation, the intervention had little overall effect on antibiotic use,16 and patients who were prescribed a new or different antibiotic after the initial consultation were excluded in the current analysis. Therefore, the authors think the trial intervention is unlikely to have biased the present findings. The exclusion of patients who changed antibiotics was also to clarify the definition of both exposure and recovery time, for example, antibiotics might be changed because of evidence of resistance, which could affect outcomes. A relatively small number of patients fell into this category, and the researchers feel that their exclusion is unlikely to have biased the findings. Finally, data on antibiotic consumption provided by patients were used, which may not be as accurate as medication adherence monitoring containers or measurement of antibiotic levels in blood or urine.27The main limitation of this study is the risk of residual confounding from unmeasured confounders such as comorbidities and the current UTI symptom duration, which might affect antibiotic-prescribing decisions but were not recorded in the POETIC study.28 In addition, the evidence from placebo-controlled trials is scarce. Only three such trials reported symptom duration in a review on the natural course of uncomplicated UTI in females up to November 2019.29 Their results showed that complete symptom recovery could occur in 18% (up to 3 days) to 54% (up to 6 weeks) of the placebo arm, with most improvement occurring in the first 9 days. This is consistent with the present finding, estimating that 50% of those who did not consume antibiotics would recover completely by day 9.A recent Cochrane review on antibiotics efficacy for UTI commented on the lack of data to evaluate time to symptomatic recovery.30 With a higher dose of ibuprofen ∼70% of females recovered by day 7 compared with 82% for fosfomycin.12 In addition, recovery time prolonged with diclofenac (4 days) compared with norfloxacin (2 days).31 No-antibiotic management may be suitable for females with mild to moderate symptoms, with caution about potential risk of pyelonephritis.12,30,31Moreover, antibiotics were found to be superior to no-antibiotic management strategies, such as painkillers, for uncomplicated UTI in females. While ∼40% of females recovered by day 4 with ibuprofen, ∼70% recovered with pivmecillinam.14 However, many females with UTI symptoms make a good recovery without antibiotic treatment and only mild symptoms remain . They may choose to delay antibiotic treatment and/or consider alternative treatments for their symptoms.10,32 The present results may help informing such a shared decision-making approach if patients were aware of the likelihood of recovering within 14 days without antibiotics. These strategies are particularly useful in younger patients and in those with lower risk for pyelonephritis10,31,33 and could lead to a reduction in antibiotic use and risk of resistance.26 Attention should focus on trying to identify these females, particularly as it is possible that some of them do not have bacterial infections , or that their immunity are able to self-limit the infection.The present study found an association between antibiotic consumption and shorter time to recovery in females with uncomplicated UTI in primary care, which is consistent with evidence from trials suggesting net overall benefit from antibiotics.There is also a need for further studies quantifying the risk and predictors of complications associated with UTI managed with and without antibiotics.


It is an outstanding solution for protecting the environment using manufactured sand instead of natural river sand in concrete. In this paper, tunnel granite muck was processed into low carbon, coarse and fine aggregates, and low carbon aggregates were used to prepare bridge concrete. Meanwhile, the mechanical properties, anti-permeability, and frost resistance of concrete were investigated. The results demonstrated that the concrete prepared using low carbon aggregate had higher mechanical properties than concrete prepared using river sand. The chloride ion penetration resistance of concrete using low carbon aggregate is better than that of concrete using river sand, and frost resistance has been improved. With the rapid decline of natural sand resources in the main rivers and lakes, the enhancement of ecological protection, and the restriction of mining through prohibitive mining policies, some highway and railway infrastructure have processed tunnel muck according to local conditions into mechanical sand aggregate, which is used to formulate concrete for tunnels and bridges ,2,3. It The utilization of tunnel muck could reduce the disposal of solid waste, reduce the effect of muck on farmland and river courses, alleviate the destruction of mountains and vegetation caused by stone material collection, and maintain the integrity of the ecological landscape. At the same time, it is an effective measure when using electric dust collection or washing methods to reduce environmental pollution. Bellopede et al.  thought As one of the important components of concrete, the quality of fine aggregate has an important influence on the working properties of a concrete mixture and the mechanical properties of hardened concrete. Natural river sand as a high-quality concrete fine aggregate has been nearly exhausted, and its exploitation destroys the ecological balance. In this situation, concrete producers began to use manufactured sand to gradually replace natural river sand to solve the problem of building sand. In recent years, many scholars have learned about the physical properties of manufactured sand ,7,8, theAt present, more and more road and bridge engineering projects are using manufactured sand to make concrete structures or concrete cement pavements. This study uses manufactured sand instead of river sand to prepare concrete and explores the difference between the concrete’s mechanical properties and durability properties through testing the concrete’s mobility energy, compressive strength, flexural strength, tensile strength, elastic modulus, and chlorine ion permeability. This study effectively solves the shortage of aggregate and has an important guiding significance for the utilization of tunnel muck.Cement: the cement was ordinary Portland cement P·O 42.5 from Shandong Shanshui Cement Group Co., Ltd. , and its basic properties are shown in Fly ash: grade II fly ash was purchased from Chiping Xinyuan environmental protection building materials Co., Ltd. , with a burning loss of 3.4% and water requirement ratio of 103%.Fine aggregate: Granite manufactured sand and river sand were used as the coarse aggregate in the experiment. The basic properties of the fine aggregate are shown in Coarse aggregate: Granite and limestone manufactured stone were used as the coarse aggregate in the experiment. The crushed stone was composed of 5–10 and 10–20 grades and the mixing ratio was 3:7. Among them, the granite gravel water absorption was 0.8%, mud content was 1.0%, and the crushing value was 12.5%. Crushed limestone water absorption was 0.6%, mud content was 0.6%, and the crushing value was 10.5%.The concrete mix proportions are illustrated in The workability of the concrete was measured according to GB/T 50080-2016 (standard for test methods of performance on ordinary fresh concrete).The compressive strength , flexural strength , splitting tensile strength , and elastic modulus  of concrete were measured according to GB/T 50081-2019 . All specimens were cured for 24 h. After curing for 24 h, the molds of the specimens were removed, and the specimens were kept in a concrete curing room (temperature 20 °C ± 2 °C and relative humidity greater than 95%). After curing the specimens for 5 d, 7 d, 28 d, and 90 d, compressive strength, flexural strength, splitting tensile strength, and elastic modulus were tested, respectively.The electric flux and RCM method were recorded in accordance with GB/T 50082-2009 (standard for test methods of long-term performance and durability of ordinary concrete). The cylinder specimens (100 mm diameter × 50 mm length) were prepared, with 3 specimens for each age. In total, 6 specimens were needed for the electric flux and 6 specimens were needed for the RCM method. After being cured for 28 d and 180 d, the chloride ion permeability resistance of the concrete specimens was tested using the electric flux and RCM method.The ability of the concrete samples to resist chloride ion penetration was evaluated using the RCM method of JGJ/T 193-2009 (standard for inspection and assessment of concrete durability) and the NEL method of CCES01-2004 (guide to durability design and construction of concrete structures).The freeze–thaw resistance of concrete was investigated according to GB/T 50082-2009 (standard for test methods of long-term performance and durability of ordinary concrete). After being cured for 28 days, three concrete specimens (100 × 100 × 400 mm) were frozen for 4 h and thawed in water for 4 h. After 25 freeze–thaw cycles, the relative dynamic modulus of elasticity of the concrete specimens was tested. After 300 freeze–thaw cycles, the experiment was stopped. Concrete is frost-resistant when its relative dynamic modulus of elasticity decrease is lower than 60% after n cycles.− Spacing factor L (mm).−1).− Specific surface α (mm− Air content A (%).The air bubble characteristic parameters in hardened concrete were tested according to JTJ 270-98 (water transport engineering concrete test code). Tests were performed using three polished concrete specimens 100 × 100 × 20 mm cut from cube specimens. Results of measurements were available as a set of standard parameters for air void microstructure characterization:The working performance of the concrete prepared for the tests is shown in It is very clear that the use of manufactured sand reduces the slump of the concrete mixture, which can be attributed to the physical properties of manufactured sand. Visually, the particle shape of manufactured sand is more angular than natural sand. There is a higher friction force among the particles, weakening the lubrication effect of mortar and thus lowering the flowability of the fresh concrete. The lithology of virgin rock, the surface texture of particles, and defects caused by mechanical crushing of manufactured sand determine the adsorption capacity of the particle surface on the adsorption water reducer and affect the fluidity of concrete . FurtherIn addition, the use of manufactured sand reduces the air content of concrete because it is difficult for air bubbles to remain in the manufactured sand mortar. The workability of the concrete was further reduced by decreasing the air content. Thus, manufactured sand affects the workability of fresh concrete through its characteristics and the changes of the air content in fresh concrete.3, which can react with Ca(OH)2 generated by cement hydration, resulting in an increase in the cohesive force of the mixture [The strength of concrete prepared using low carbon aggregate is thought to be largely correlated with the bond of manufactured sand and cementing materials. Compared with natural sand, manufactured sand is more firmly embedded in pastes, mainly because the surface of manufactured sand has a crushed, fractured surface, which is beneficial to the contact between manufactured sand and pastes. The stone powder with a particle size less than 75 um that comes from the mechanical crushing of virgin rock contributes to filling the voids in concrete. Furthermore, the main component of rock is CaCO mixture ,19.Comparing the experimental results between the GM and GR groups shows that the compressive strength of concrete prepared with granite aggregate is higher than that with limestone aggregate, and the compressive strength of GM is 9%~14% higher than LM at each age. Compared with limestone, the granite aggregate used has higher water absorption, which reduces the water–binder ratio in the interface transition zone, improves the cohesiveness between the slurry and the aggregate, and improves the compressive strength of the granite concrete. In addition, under the same stress level, granite has greater deformation, which can alleviate the effect of stress concentration, thereby improving the compressive strength of concrete.The flexural strength of concrete increases with age; however, the flexural strength of concrete prepared with manufactured sand is basically equivalent to that with natural sand. Comparing the experimental results of the GM and GR group, the manufactured sand has no significant effect on the flexural strength. The experimental results of the GM and LM group show that the flexural strength of the concrete made of granite aggregate is higher than that of the limestone aggregate. As the age increases, the difference of strength between the two tends to decrease.The splitting tensile strength of concrete prepared using low carbon aggregate is shown in The elastic modulus of concrete prepared with manufactured sand and with natural sand is shown in −12 m2/s.As shown in The frost resistance of concrete with different aggregates is shown in Air-void structure is the key parameter that affects the frost resistance of concrete using research results of the publication ,21. The (1)Low carbon aggregates from tunnel muck affects the workability of fresh concrete through its characteristics and the changes in air content in fresh concrete. Therefore, the mix ratio should be optimized to obtain concrete prepared using low carbon aggregate with a better working performance in actual engineering applications.(2)The GM specimens show higher compressive strength. At 90 d, the compressive strength of GM was 14.6% higher than that of GR. The flexural strength of concrete prepared with manufactured sand is basically equivalent to that with natural sand. Compared to the GR specimens, the splitting tensile strength of GM decreased by 15%~20%. In addition, low carbon aggregates from tunnel muck reduces concrete’s elastic modulus because of the low elastic modulus of coarse granite aggregate; the elastic modulus of the GM specimens is 26.3% lower than those of LM at 5 d.(3)The ability to resist chloride ion penetration in concrete prepared using manufactured sand is better. Compared with river sand (GR), the electric flux and chloride ion diffusion coefficient of the specimens with granite manufactured sand (GM) decreased by 30% and 24.6%, respectively.(4)Concrete specimens with low carbon aggregates show better frost resistance properties. The concrete with the limestone aggregate (LM) could withstand the freeze–thaw cycle 150 times; however, the concrete samples with low carbon aggregates (GM or GR) could withstand the freeze–thaw cycle 300 times, indicating that low carbon aggregates can be used in special service environments.(5)In actual projects, low carbon aggregates prepared from tunnel muck can be used to prepare high-strength, high-performance, and durable concrete that meets the requirements of the project by controlling the quality of the granite manufactured sand and selecting a reasonable mix ratio.


Immunoglobulin G4 (IgG4)-positive plasma cells play a pivotal role in the pathogenesis of IgG4-related diseases, in which fibrosis is observed in various organs. Lesions often develop in the lacrimal gland and orbit; however, uveitis and scleritis are also noticed. We present the case of a 55-year-old woman who was diagnosed with eosinophilic pneumonia in November 2021 at the Department of Collagen Disease of another hospital. She was treated with 25 mg of oral prednisolone. On January 11, 2022, when the dose of prednisolone was reduced to 7.5 mg, she began complaining of conjunctival hyperemia in the left eye, and a few days later, eye pain was also reported. On January 17, she visited an ophthalmology clinic and was prescribed betamethasone and tacrolimus eye drops, and was subsequently admitted to our hospital. The blood test results showed a high IgG4 level. We consulted the collagen disease physician to evaluate her previous data. The serum IgG4 level collected on December 6, 2021, was 608 mg/dL, and a re-examination of the bronchial biopsy tissues on December 2, 2021, confirmed 48% of IgG4-positive cells. Thus, pulmonary lesions appeared to be IgG4-related pathologies. Increasing the oral prednisolone dose to 30 mg improved the scleritis. As seen in this case, the possibility of an IgG4-related disease should be considered when scleritis is observed in a patient diagnosed with eosinophilic pneumonia. Immunoglobulin G4 (IgG4)-related diseases involve the infiltration of IgG4-positive plasma cells into various organs, including the pancreas causing organ damage due to fibrosis . LesionsIncreased peripheral blood eosinophils and eosinophil infiltration in diseased tissues have been reported to be frequently observed in IgG4-related diseases . AlthougA 55-year-old woman was diagnosed with asthma and sinusitis in 2015. Further examination led to the diagnosis of eosinophilic pneumonia and she was treated with systemic administration of 25 mg of prednisolone since November 2021. On January 11, 2022, she started to complain of conjunctival hyperemia in her left eye, and a few days later, eye pain was noted. on January 17, she visited a nearby ophthalmology clinic and was prescribed 0.1% tacrolimus eye drops twice a day and 0.1% betamethasone eye drops four times a day for the left eye; however, no improvement or changes were observed. Therefore, she was referred to our hospital on March 2. At the first visit to our hospital, the dose of systemic prednisolone was reduced to 7.5 mg because her eosinophilic pneumonia was well controlled. Visual acuity was 0.8 (0.9) and 0.6 (1.2) in the right and left eyes, respectively, and the intraocular pressure was 8 mmHg in both eyes. There were no intraocular inflammatory findings; however, nodular scleritis was observed on the left temporal side , and she was referred to the Department of Collagen Disease of another hospital where she was treated for eosinophilic pneumonia. When retested using the previously collected samples in the Department of Collagen Disease, the serum IgG4 level assessed on December 6, 2021, was 608 mg/dL, and the bronchial biopsy tissue on December 2, 2021, showed 48% IgG4-positive cells. Based on these findings, the collagen disease physician diagnosed the patient with IgG4-related lung disease instead of eosinophilic pneumonia . A 30 mg of prednisolone dosage was started orally on the same day. On May 15, 2022, computed tomography of the neck, chest, and abdomen was performed, which showed no abnormal findings, except for the remission of pulmonary lesions. Systemic administration of prednisolone improved conjunctival hyperemia and eye pain in the left eye (Figure She was given 0.1% tacrolimus eye drops twice a day, and 0.1% betamethasone four times a day was continuously administered. Her oral prednisolone dosage was reduced to 17.5 mg, and checkups were continued Figure .IgG4-related diseases are typically characterized by fibrotic and sclerotic changes observed in multiple organs due to the infiltration of lymphocytes and plasma cells . In the In the present case, a patient who was treated for eosinophilic pneumonia developed scleritis, and during follow-up, the pulmonary lesions were found to be an IgG4-related disease. Similarly, we reported a case of a conjunctival mass in a patient who was treated for eosinophilic pneumonia and eosinophilic sinusitis and was finally diagnosed to be an IgG4-related disease [Based on the results of previous prospective studies, the percentage of peripheral blood eosinophils increases by 9% and 38% in healthy subjects and in those with IgG4-related diseases, respectively . MoreoveWhen scleritis is present in patients who were diagnosed with eosinophilic pneumonia, IgG4-related disease should be considered because of the increased number of eosinophils in peripheral blood in patients with IgG4-related diseases.