Enabling real-time monitoring and control of the biomanufacturing processes through product quality insights continues to be an area of focus in the biopharmaceutical industry. The goal is to manufacture products with the desired quality attributes. To realize this rigorous attribute-focused Quality by Design (QbD) approach, it’s critical to support the development of processes that consistently deliver high-quality products and facilitate product commercialization. Time delays associated with off-line analytical testing can limit the speed of process development. Thus, developing and deploying analytical technology is necessary to accelerate process development. In this study, we have developed the Micro Sequential Injection (µSI) process analyzer and the Automatic Assay Preparation Platform (A2P2) system. These innovations address the unmet need for an automatic, online, real-time sample acquisition and preparation platform system for in-process monitoring, control, and release of biopharmaceuticals. These systems can also be deployed in laboratory areas as an off-line analytical system and on the manufacturing floor to enable rapid testing and release of products manufactured in a GMP environment.

Agitated saline microbubbles (MBs) is a common contrast agent for determining right-to-left shunt (RLS) by the contrast Transcranial Doppler (c-TCD). The size of the generated bubbles is not standardized in clinical practice. The microbubbles were generated using the recommended manual method by reciprocating motion through two syringes. The bubble size distributions (BSD) were measured using the microscopic shadow imaging technique. The results show that the diameter of MBs is mainly distributed between 10-100 µm, the mean bubble size is between 21-34 μm, the Sauter mean diameter (D 32) is mainly between 50-300 μm, and the standard deviation (SD) is between 6-17 μm in 60 experiments. It provides a more accurate basis for the recommended manual method instability. The high variance values of the BSD indicate that the manual method has low stability and repeatability. The results of this study can be useful for further improvement of the reliability of c-TCD in detecting RLS. Research Highlights This study provided the first detailed descriptions of the size distribution of microbubbles in a flowing contrast agent by the microscopic shadow imaging technique. It reveals significant differences in the bubble size of manual foaming during repeated manipulations for each individual and between individuals.

Title of manuscript : Forme fruste of scleroderma and autoimmune hearing loss in a young adult with X linked agammaglobulinemia Authors-Munish Arora, Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and research, Chandigarh, IndiaPallavi Nadig, Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and research, Chandigarh, IndiaSanchi Chawla, Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and research, Chandigarh, IndiaSaniya Sharma, Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and research, Chandigarh, IndiaAmit Rawat, Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and research, Chandigarh, IndiaRamandeep S. Virk, Department of Otorhinolaryngology, Post Graduate Institute of Medical Education and research, Chandigarh, IndiaAnkur Kumar Jindal, Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and research, Chandigarh, India.

Objectives To determine fertility outcomes after diagnosing genital tuberculosis followed by anti-tubercular therapy (ATT) and response to different subfertility treatment modalities. Hysteroscopy and laparoscopy data were also analysed to determine whether or not starting ATT early on in the course of tuberculosis treatment was more effective. Study design Among the infertile women, presented in department Reproductive Medicine in Bansal Hospital, Bhopal from Feb 2014 to June 2022, who underwent diagnostic hysteroscopy and laparoscopy, 1083 women having positive finding(s) suggestive of tuberculosis were received anti-tubercular therapy for at least six months. Retrospectively, we analysed the pregnancy outcome of these women after receiving anti-tubercular therapy followed by different subfertility treatments. Results In vitro fertilization (IVF) was a primary modality of treatment. 551(55.88%) women undergoing IVF with their oocytes resulted in 348(63.15%) clinical pregnancies, 264(47.91%) ongoing pregnancies, 84(15.24%) first-trimester miscarriages, and live birth in 246(44.64%) women. Clinical pregnancy rate, ongoing pregnancy rate, and live birth rate all show a statistically significant (P = 0.039) improvement when illness is diagnosed early through hystero-laparoscopy and treated with ATT, followed by fertility therapy. Conclusions Diagnostic hysteroscopy and laparoscopy may be performed to examine high-risk infertile individuals by analysing the reproductive system, including tubal factor. This helps choose a treatment strategy and forecast its success. This study shows that if ATT initiated at early stage as suggested by endoscopy findings IVF reproductive outcomes equivalent to the background population. Late-stage ATT results are often quite dismal, despite the fact that IVF and other adjuvant therapy may improve fertility.

An unusual case of eccrine porocarcinoma on the axilla with nodal involvementSabita Maharjan1, Oshan Shrestha1, Reetu Baral1, Amit Bhattarai21Department of Pathology, Nobel Medical College Teaching Hospital, Biratnagar, Nepal2Department of General Surgery, Nobel Medical College Teaching Hospital, Biratnagar, NepalCorrespondence:Sabita Maharjan, Department of Pathology, Nobel Medical College Teaching Hospital, Biratnagar, 56700, Nepal, Tel: +9779841034653; Email: sabimaharzan@gmail.comKey words: Dermatology, General surgery, Oncology

Early fatigue failure would happen occasionally even in a well-designed crankshaft. The nonuniformity of microstructure (including micro-defects) plays an important role in crankshaft’s early fatigue, which can induce the scatter of strength properties and even relatively large micro-defects. Characterizing the microstructural nonuniformity through statistical distribution of initial damage, scatter of strength and fatigue life can be described in a unified form. To determine the statistical distribution of initial damage, relationships between the initial damage dispersion and the scatter of tensile/fatigue strength or impact energy sampling test data have been systematically investigated. Based on the statistical distribution of initial damage and fatigue limit, the reliability and early fatigue probability of crankshaft’s fatigue strength design can be analyzed. To ensure sufficient reliability against early fatigue failure, it is found that the safety factor in design should be determined based on the actual strength dispersion rather than a predetermined empirical value.

Contact among animals is crucial for various ecological processes, including social behaviors, disease transmission, and predator-prey interactions. However, the distribution of contact events across time and space is heterogeneous, influenced by environmental factors and biological purposes. Previous studies have assumed that areas with abundant resources and preferred habitats attract more individuals and, therefore, lead to more contact. To examine the accuracy of this assumption, we used a use-available framework to identify landscape factors influencing contact locations. Our study focused on two wild pig populations in Florida and Texas, USA. We employed a contact-resource selection function (RSF) model, where contact locations were defined as used points and locations without contact as available points. By comparing the contact RSF with a population-level RSF, we assessed the factors driving both habitat selection and contact. We found that the landscape predictors (e.g., wetland, linear features, and food resources) played different roles in habitat selection and contact processes for wild pigs in both study areas. This indicates that pigs interacted with their landscapes differently when choosing habitats compared to when they encountered other individuals. Consequently, relying solely on the spatial overlap of individual or population-level RSF models may lead to a misleading understanding of contact-related ecology. Our findings challenge prevailing assumptions about contact and introduce innovative approaches to better understand the ecological drivers of spatially explicit contact. By accurately predicting the spatial distribution of contact events, we can enhance our understanding of ecological processes and their spatial dynamics.

Heparin-induced Thrombocytopenia with Normal Platelet Count: A Cautionary Tale of Delayed DiagnosisAhmed Elkheshen MD1, Marawan Elmassry MD1*, Sierra Sullivan MD1, Ricardo Franco MD1, Abbie Evans MD1, Kavya Bharathidasan MD1, Arunee Motes MD1, Sameer Islam PhD3, Ebtisam Attaya Islam PhD21-Department of Internal Medicine, Texas Tech university Health Sciences Centre, Lubbock, TX, USA.2- Department of Pulmonology and Critical Care Medicine, Texas Tech university Health Sciences Centre, Lubbock, TX, USA.3- Department of Gastroenterology and Hepatology, Texas Tech university Health Sciences Centre, Lubbock, TX, USA.*Corresponding Author: Marawan Elmassry MDTexas Tech University Health Sciences Centre at Lubbock, Texas, USA.3601 4th street, Lubbock, TX 79430.Telephone/ Fax: +1-806-773-2831E-mail: Marawan.elmassry@ttuhsc.eduConflict of interest: The authors have no financial conflicts to disclose.Patient’s consent: Written informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policy.Keywords :HIT, Heparin, Thrombocytopenia, Heparin Induced Thrombocytopenia, Platelet Count.

In this paper a distributed event-triggered control of an islanded network of microgrids is proposed. Microgrids are connected to their neighbors from the point of view of energy exchange and data communication level. The control objective consists of driving the state of charge of batteries to a desired attractor, managing the connections, and disconnections of energy transfer. The control design and asymptotic convergence analysis is based on hybrid dynamical system theory, considering the state of charge of batteries and powers as continuous-time variables and the connections and disconnections among microgrids as discrete-time variables. The stability properties of a given attractor are guaranteed even when an unintentional connection/disconnection of any microgrid element occurs or when any battery is saturated in any of its bounds. This attractor is selected as a trade-off between reaching a small size of a consensus neighbourhood among the state of charge of the batteries and reducing the energy losses associated with the interconnections between microgrids.

Ferroptosis is a new non-apoptotic form of regulatory cell death, which is characterized by intracellular iron overload and excessive accumulation of lipid peroxides and reactive oxygen species (ROS). Ferroptosis is closely related to intracellular iron, amino acid, and lipid metabolism disorders. Ferroptosis is increasingly recognized as an important process mediating the pathogenesis and progression of acute ischemic stroke, and it can be involved in influencing acute ischemic stroke and acute ischemic stroke risk factors atherosclerosis, atrial fibrillation, hypertension, diabetes mellitus, and obstructive sleep apnea. Therefore, understanding the mechanisms of ferroptosis regulation in different diseases may have significant implications for the preventive treatment and improvement of prognosis in patients with acute ischemic stroke and patients with risk factors for acute ischemic stroke. This article reviews not only the specific important mechanisms of ferroptosis in the development of acute ischemic stroke, but also the relevant associations between risk factors for acute ischemic stroke and ferroptosis, and describes the current limitations and future directions of ferroptosis in the pathogenesis of acute ischemic stroke and its risk factors.

Abstract There is increasing interest in employing Single-Cell Analysis (SCA) technologies to improve the efficiency of renal disease diagnosis and treatment. Nevertheless, comprehensive studies summarizing and analyzing research trends in the field are lacking. There is increasing interest in employing Single-Cell Analysis (SCA) technologies to improve the efficiency of renal disease diagnosis and treatment. Nevertheless, comprehensive studies summarizing and analyzing research trends in the field are lacking. This article discusses the use of bibliometric analysis to evaluate the progress and potential of Single-Cell Analysis (SCA) technologies in the field of kidney disease. The study identified 1,606 articles and reviews published between 1999 and 2023, involving 11,737 authors from 2,317 institutions across 67 countries or regions. The major contributors to SCA in kidney disease were highlighted, including top authors, institutes, countries, and journals. Research hotspots included molecular and pathological aspects, with disease-, molecular-, and pathological-related keywords such as expression, EGFR, gene-expression, activation, gene, cell, protein, mechanism, mutation, inflammation, resistance, apoptosis, and T-cell. Key kidney-related disease keywords included SLE, AKI, CKD, renal fibrosis, diabetic kidney disease, nephrotic syndrome, IgA nephropathy, and kidney transplantation. The authors note that the field of SCA in kidney-related disease research is rapidly growing, with the potential for further expansion. SCA technologies could provide novel diagnostic, therapeutic, and prognostic approaches and support routine clinical diagnosis and individualized treatment.

The coronavirus disease 2019 (COVID-19) has shown unexpected viral infection traits. Initially thought to affect respiratory health primarily, it also involves the gastrointestinal system. However, many complications during the pandemic were caused by the virus, including neurological, cardiovascular, dermatological, and metabolic issues. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has also been linked to cardiac complications, such as myocardial infarction, in individuals without cardiovascular risk factors. SARS-CoV-2 vaccines exacerbated the situation with possible adverse events (AEs). Vaccine side effects, like thromboembolic events, can be life-threatening or simply bothersome. Postural orthostatic tachycardia syndrome (POTS) is a nonlethal cardiac complication seen with COVID-19 and its vaccines. In this review, we summarized the POTS-COVID-19 relationship comprehensively.

A document by Ali Pourshaban-Shahrestani. Click on the document to view its contents.

Interleukin-12 (IL-12) is known to exert anti-tumor immune effects by promoting the activation and proliferation of T cells and NK cells within the immune system. However, clinical trials have observed systemic toxicity associated with the administration of IL-12. This has shelved development plans for its use as a cancer therapeutic drug. Therefore, it is critical that we perform a systematic evaluation of the toxicity and safety of repeated IL-12 administration. In this study, we conducted a comprehensive evaluation of the toxicity and safety of repeated IL-12 administration in rhesus monkeys by assessing its effects on the immune system, organ function, and vital signs. Our findings provide accurate dosage selection and administration plans that minimize the risk of adverse reactions in patients while ensuring therapeutic efficacy.

Objective: To evaluate both short and mid-term effects of maternal COVID-19 on cardiac functions of fetuses and children. Methods: The present case-control study was conducted on 36 pregnant women who had COVID-19 infection in the second trimester of pregnancy and 30 pregnant women as healthy controls. Fetal, neonatal and infant cardiac functions were compared between the groups. Assessment of fetal cardiac functions were performed in the last trimester of the pregnancy at least 6 weeks after the recovery of infection. The first postnatal echo was performed within the first two weeks and the follow-up (second) echo was performed in the 6-8 weeks of life. Results: The demografic data were similar between groups. Interventricular septum and left ventricular posterior wall end-diastolic dimensions were significantly higher in the study group in both fetal, neonatal and infant periods. Impaired diastolic functions of right and left ventricles were detected and myocardial performance indexes with tissue doppler imaging of both lateral walls and septum were significantly higher than controls at all periods. Conclusion: Maternal COVID-19 seems to have a global impact on cardiac functions of babies in the short and mid-term periods after maternal recovery.

BACKGROUND: Colour M–mode propagation velocity (Vp) is an echocardiographic parameter that represents relaxation of the left ventricular (LV) and the ratio of peak E-wave velocity and flow propagation velocity (E/Vp) can be used to measure pulmonary capillary wedge pressure (PCWP) estimation which is almost equivalent to invasively measured PCWP. The correlation between propagation velocity (Vp) with standard left ventricular diastolic function parameters and E/Vp with PCWP in patients with acute heart failure with preserved ejection fraction (HFpEF) has not been widely studied. This study aimed to determine the correlation of Vp in the assessment of left ventricular diastolic function in acute heart failure patients with HFpEF. METHODS: This research is an observational analytical study using a cross–sectional study design conducted from April to June 2022. The subjects of this study were patients diagnosed with acute HFpEF and treated at Dr. Soetomo General Academic Hospital, Surabaya. Patients with heart rhythm disturbances, moderate to severe valvular heart disease, and congenital heart defects were excluded from this study. Patients were measured for diastolic function including mitral valve early mitral inflow velocity (MV E Velocity), mitral peak velocity of early filling (E’) (E’ Septal and E’ Lateral), left atrial volume index (LAVI), The maximal tricuspid regurgitation velocity (TR V Max), Vp, the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/E’), the ratio between early and late ventricular filling velocity (E/A) and E/Vp Ratio. N-terminal-pro hormone B-type natriuretic peptide (NT–ProBNP) examination was also performed on study subjects as an additional diagnosis of acute heart failure. RESULTS: There were 33 patients who met the inclusion and exclusion criteria and were included in our study. There were 26 patients (78.8%) with grade I diastolic dysfunction, 4 patients (12.1%) with grade II diastolic dysfunction, and 3 patients (9.1%) with grade III diastolic dysfunction. There is a strong positive correlation between Vp with parameters E’ Septal (p = < 0.001; r = 0.636) and E’ Lateral (p = < 0.001; r = 0.650). Vp is negatively correlated with the ratio E/E’ (p = 0.029; r = –0.37). The PCWP estimate with E/Vp ratio had a strong correlation with the NT–Pro BNP value > 300 pg/ml in acute HFpEF patients (p = < 0.001; r = 0.726) compared to the PCWP estimate with E/E’ (p = < 0.001; r = 0.549). There is no correlation between Vp value and degree of diastolic dysfunction in patients with acute HFpEF. CONCLUSION: Vp has a strong correlation in the assessment of left ventricular diastolic function parameters with acute HFpEF. PCWP estimation using E/Vp ratio has a strong correlation with NT–ProBNP > 300 pg/ml. Measurement of Vp value and E/Vp ratio can be used to assess diastolic function and estimate PCWP in patients with acute HFpEF.

The brain-network correlates of personality traits in major depressive disorder (MDD) have not yet been investigated. Furthermore, it is still unclear whether personality traits relate to the depressive episode. This study assessed network properties, depression severity, and personality traits in patients with MDD (n=25) compared with age- and sex-matched healthy controls (n=22). MDD patients with different character traits exhibited significant differences in terms of depression diagnosis and severity of Hamilton Depression Rating Scale scores compared to the controls. The MDD patients also exhibited reduced resting state network activity between the posterior default mode network, right putamen, and right frontal pole, while self-directness (SD) was significantly less frequently diagnosed in MDD patients. In evaluating the network correlates, differences in the SD traits were significantly associated with critical brain network alterations that were not evident in other traits. To the best of our knowledge, this is the first study to provide preliminary evidence of an anomalous connectome in the SD trait in MDD, thus providing strong evidence for personalized antidepressant treatment strategies in MDD.

Cursive text detection is essential in various fields, includ- ing document analysis, scene character and optical charac- ter recognition (OCR). Despite technological advancements, accurate detection and recognition of cursive text in natu- ral scene images continued to be difficult because of differ- ences in font sizes, styles, orientations, alignments, resolu- tions, blurriness, complex backgrounds and appearance of multilingual text. Urdu is a cursive language widely spoken in many South-Asian countries. There has been a persistent need for Urdu text recognition because of its appearance in natural scenes such as signboards, car number plates, news- papers, magazines, etc. Moreover, Urdu text detection is challenging due to its complex writing style, which includes joined writing, variations in the same characters, numerous ligatures, multiple baselines, and other factors. This paper proposes two hybrid models for resolution-free cursive text detection and recognition. Firstly, a convolutional neural net- work (CNN) is used for text detection, which is repeated with the Visual Geometry Group (VGG-16). Secondly, for text recognition, Long Short-Term Memory (LSTM) model is used on the extracted features from CNN and VGG-16 separately. The proposed hybrid models CNN in combination with LSTM and VGG-16 in combination with LSTM outperform the ex- isting ones by achieving 91% and 96% accuracy, respectively.

Understanding wildlife behavior is crucial for effective conservation and management. However, studying the behavior of diverse species presents challenges due to their complexity and the availability of data. To address this, we present a universal indicator for assessing the ease of humans learning wildlife behavior. This indicator incorporates species familiarity, behavioral complexity, and data availability, providing a standardized framework for evaluating learnability. Applying the indicator to a diverse range of species reveals insights into research priorities and knowledge gaps. The indicator enables researchers, educators, and policymakers to prioritize efforts, enhance conservation strategies, and facilitate effective wildlife management and education initiatives. Its application has the potential to contribute to a more comprehensive understanding of wildlife behavior on a global scale. While the indicator is a valuable tool, its limitations necessitate ongoing data collection and refinement. The universal indicator advances our understanding of wildlife behavior and informs evidence-based conservation and management strategies.

Active suspension plays a pivotal role in modern vehicles. In this paper, an adaptive PID controller of active suspension systems based on RBF neural network (RBF-NN) is developed. A quarter-car suspension system with two degrees of freedom is demonstrated. The values of proportional, integral, and derivate components are obtained by using Ziegler-Nichols(Z-N) tuning method and RBF-NN methods. The suspension system is perturbed using the sine function. Simulated in the Simulink environment is the quarter-car model. Passive suspension systems, adaptive PID controller utilizing the Z-N tuning approach, and adaptive PID based on the RBF-NN method for active suspension systems are compared. The active suspension with PID control based on the RBF-NN outperformed the active suspension with PID control utilizing the Z-N tuning approach and passive suspension, according to simulation data. The comparison demonstrates the proposed control method’s superior features

Exponential model for population growth (exponential model) is a cornerstone to evaluate population dynamics in Population Ecology field. Here, we used a didactic experiment to teach exponential model for an undergraduate course of Population Ecology. We built nine populations of weevils with three different initial sizes: eight, 16, and 32 individuals with three replicates each. We furnish them equal food resource availability, and count their sizes weekly across 12 weeks. We estimated the intrinsic and population growth rates (i.e., r and dN/dt parameters) by trials and errors with an exponential model build in an Excel spreadsheet. Replicates with eight and 16 individuals reached the highest values of r and dN/dt, while replicates with 32 individuals reached the lowest values. Beyond of exponential model, we observed two density dependency issues acting in populations. First, in the lowest initial population sizes we observed the effect of demographic stochasticity acting in diminishing the number of individuals in one population. Second, we observed the intraspecific competition reducing r values in largest initial populations. Therefore, we highlight the importance of didactic experiment into learning exponential model in Population Ecology course.

Phenols are ubiquitous substructures in natural products and bioactive compounds. However, practical methods for the direct construction of phenols under mild conditions remains challenging. Herein, a photocatalytic acceptorless dehydrogenative aro-matization of cyclohexanones or cyclohexenones at room temperature has been developed. The reaction features the visible-light and cobalt co-catalyzed sequential dehydrogenation of in-situ formed enol silyl ethers, which are regarded as a challenging process. This operationally simple method enables the synthesis of a series of phenols with diverse substitution patterns from cyclohexanones or cyclohexenones. Moreover, diverse substituted 1,2-, 1,3-, and 1,4-benzenediols were obtained from cyclo-hexanediones, providing a general and straightforward method for the synthesis of phenols from simple starting materials un-der mild conditions

Background: Food-induced immediate response of the esophagus (FIRE) is a new phenomenon that has been described in eosinophilic esophagitis (EoE) patients. It is suspected when unpleasant symptoms occur suddenly on contact of the triggering food with the esophageal surface and recur with repeated exposures. It can often be mistaken for pollen-food allergy syndrome (PFAS) and solid food dysphagia. Data on FIRE is limited to one survey study and case reports, and there are no screening studies conducted on either adults or children with EoE. In this study, we aimed to screen children aged ≥7 years old with EoE for FIRE. Methods: Demographic data were collected from medical records. A questionnaire about FIRE was applied to all participants. Skin prick tests (SPTs) were done on suspected patients to identify the triggering foods. FIRE is defined as suitable clinical symptoms with suspected food allergen exposure. Results: Seventy-eight patients (74.4% male, median age: 13.5 years) were included. Unpleasant and recurrent symptoms distinct from dysphagia with specific foods were reported in %16.7 of the patients, all of whom had concomitant allergic rhinitis (AR). The symptoms described by almost all patients were oropharyngeal itching and tingling (PFAS: 15.3%) excluding only one patient reporting retrosternal narrowing and pressure after specific food consumption (FIRE: 1.2%). Conclusions: Although definitive conclusions regarding the true prevalence of FIRE cannot be made, it does not seem to be common as PFAS. However, it deserves questioning particularly in the presence of concurrent AR and/or PFAS in children with EoE.

Tropical urban environments reveal a strong association of CD45RBloCD161+ Th2 subset to allergic rhinitis To the Editor:Allergic airway diseases such as allergic rhinitis (AR) affects more than 400 million individuals worldwide and afflicts substantial health and economic morbidity. [1] AR is strongly associated with a type 2 response, characterized by the cytokines IL-5, IL-4 and IL-13. However, the key drivers behind AR immunopathogenesis remained to be elucidated. This study aims to identify critical pathogenic cell populations associated with AR using the Singapore System Immunology Cohort (SSIC) [2] and a clinician-diagnosed paediatric cohort with active AR manifestation (Supplementary Table 1 ). In both cohorts, the eosinophilic nature of AR was confirmed by higher blood eosinophil numbers (Supplementary Figure 1 ).Whole blood gene expression analysis revealed a total of 23 probes representing 20 unique genes were associated with AR in the SSIC (Table 1A ). To account for ethnicity and environmental influences we validated our findings in BAMSE population-based cohort comprising of Swedish adolescents. Table 1B shows 11 DEGs which was also associated with AR, confirming the transferability of our findings to other populations. For the top DEGs that reached nominal significance in the SSIC we performed an Ingenuity Pathway Analysis (IPA). Supplementary Table 2 revealed important pathways related to hypersensitivity and inflammation and also functional enrichment for eosinophils, basophils and mast cells. In particular, functional activation of Th2 was highlighted as a key pathway for AR pathogenesis. As CRTH2 was reported to be expressed by cell types involved in the eosinophilic response, [3] an unsupervised cluster analysis was performed on the CRTH2+ subset in PBMC of individuals from SSIC (Figure 1 A and B ) to determine CRTH2+ subsets associated with AR. We found that CD161+Th2 subsets in particularly to be strongly associated with AR (Figure 1C and D ) (Supplementary Figure 2 ). Further characterization found that the marker CD45RB to be significantly downregulated on CD161+Th2 cells of AR individuals (Figure 1E ). Low CD45RB expression on T cells is indicative of a mature phenotype. Interestingly, significantly higher circulatory plasma IL-5 levels (Figure 1F) . Furthermore we could also demonstrate AR individuals produced significantly higher IL-5 in an in vitro PMA-stimulation assay (Figure 1G ).While we noted a small population of IL-5 secreting conventional CD161-Th2 (cTh2), IL-5 secretion was significantly elevated in CD161+Th2 cells (Figure 1H ). Strikingly, IL-5 was found to be predominantly secreted by CD45RBlo subset in both cTh2 and CD161+Th2 (Figure 1H and I ). There was also a significant increase in the IL-5 producing CD45RBloCD161+Th2 population from the AR individuals (Figure 1I ). These findings confirm CD45RBloCD161+Th2 as the main producers of IL-5.We further validated our findings in a second paediatric cohort with clinically diagnosed active AR manifestations. To further refine CD161+Th2 subset that is associated with AR, we performed unsupervised PhenoGraph and UMAP clustering on CD161+Th2 (Supplementary Figure 3A and B ). Amongst the UMAP clusters, “cluster 3” was found to be significantly associated with active AR (Supplementary Figure 3C and D ). Deep characterization reveals “cluster 3” to be an IL-5 secreting CD45RBlopopulation, confirming our earlier observation (Supplementary Figure 3E ). Furthermore, this cluster appeared to be a highly differentiated population of mature CD161+Th2 cells with an activated phenotype secreting IL-2, IL-3, IL-4, IL-9 and IL-13 concomitantly (Supplementary Figure 3E and F ). Thus, the severity of eosinophilic airway allergies such as AR seems to be driven by an activated terminally differentiated CD161+Th2 subset that is able to secrete a complex set of inflammatory cytokines.The presence of CD45RBloCD161+Th2 population in both cohorts shows the persistence and pertinence of this population in the pathogenesis of AR. Both cohorts described in this study were collected in Singapore, whereby majority of the individuals are sensitized against HDM. HDM is a perennial allergen in tropical nations such as Singapore, thus T cells in atopic individuals undergo constant stimulation. This could explain the strong association observed between CD45RB expression on CD161+Th2 cells and atopy markers despite the fact that not all subjects demonstrated active AR symptoms during the collection of SSIC cohort. Taken together, our current study unifies the markers previously reported for allergic-specific Th2 subsets and provides clarity for the pathogenic Th2 subset previously reported in different allergic diseases.[4-6] Neutralizing the CD45RBloCD161+Th2 subset should disrupt the allergic response pathway, thus providing a target for lasting therapeutic interventions. Moreover, these cells may also be leveraged as a biomarker for the effectiveness of immunotherapy as well as a potential biomarker of public health surveillance of allergic individuals.