Moderate Response Research Articles

Fertilization for Growth or Feeding the Weeds? A Deep Dive into Nitrogen’s Role in Rice Dynamics in Ecuador

Rice (Oryza sativa L.) is a crucial crop for employment and agricultural output and heavily reliant on family labor. This study evaluated the effects of nitrogen levels (80, 120, and 160 kg·ha−1) on weed incidence and key agronomic variables, including vegetative growth, yield, and related traits, in Ecuador’s primary rice-growing regions, Guayas and Los Ríos. A split-plot randomized complete block design was implemented using two rice varieties (INIAP-FL-Elite and SFL-11) and three planting densities (20 × 30, 25 × 30, and 30 × 30 cm). Weed incidence was higher in Los Ríos, dominated by grasses (55.28%), while Cyperaceae (46.27%) prevailed in Guayas. The data analysis included non-parametric tests to identify significant treatment effects, debiased sparse partial correlations (DSPCs) to reveal key agronomic interactions, and principal component analysis (PCA) to identify influential traits, ensuring robust and normalized interpretations. Analysis of variance indicated significant effects for all variables, with vegetative growth (VG) most affected (p < 0.001). The number of panicles (NP) and days to flowering (DF) showed significant though less pronounced effects, while the panicle length (LP) and 1000-seed weight (TSB) exhibited moderate responses. The DSPCs highlighted the grains per panicle (GP) and total biomass (SB) as critical variables, with significant correlations between the days to flowering and the tiller count at 55 days (r = 0.750, p < 0.001) and between the vegetative growth and the total biomass (r = 0.678, p < 0.001). PCA explained 58.8% of the total variance, emphasizing the days to flowering, plant height, total biomass, and yield as the most influential traits. These findings underline the importance of integrated nutrient and weed management strategies tailored to Ecuador’s agroecological conditions.

How incentives affect commuter willingness for public transport: Analysis of travel mode shift across various cities

Incentive-based strategies tailored to individual preferences can motivate commuters to adopt public transit, potentially easing road congestion and fostering ecofriendly urban travel. However, understanding diverse responses to these incentives has been challenging due to low survey participation and certain homogeneity assumptions, limiting our knowledge of individuals’ preferences for using public transit in different cities. To address this, our study employs a latent class choice model and mixed logit model to analyze individual responses to incentives and identify key factors that influence the effectiveness of these incentives. Data for this analysis was sourced from a mobile navigation application, covering 34 cities within China, thereby enabling the analysis of individuals within each latent class to reveal their diverse preferences for using public transit within different cities. Our findings indicate significant individual differences in response to incentives, categorized into three main latent classes: Class 1 individuals exhibit minimal influence from incentives; those in Class 2 demonstrate moderate responsiveness, especially to food and shopping coupons; and Class 3 individuals, whose decision-making is significantly affected by education level, gender, and travel mode preference, show a high degree of responsiveness to incentives. These insights are invaluable for policymakers seeking to design more effective, tailored incentive schemes to encourage public transit adoption.

Functional Role of Odorant-Binding Proteins in Response to Sex Pheromone Component Z8-14:Ac in Grapholita molesta (Busck)

The plum fruit moth (PFM), Grapholita funebrana, and the oriental fruit moth (OFM), G. molesta, are closely related fruit moth species that severely damage fruit trees in Rosaceae. Both species share common primary sex pheromone components Z8-12:Ac and E8-12:Ac. The secondary sex pheromone components of PFMs consist of Z8-12:OH, Z8-14:Ac, and Z10-14:Ac, while those of OFMs include Z8-12:OH and 12:OH. Previous researchers have proved that the inclusion of Z8-14:Ac and Z10-14:Ac did not augment PFM catches but inhibited OFM catches in orchards in Europe, thereby maintaining the species-specificity of the PFM sex attractant. However, which of these components, Z8-14:Ac or Z10-14:Ac, plays the major role in inhibiting OFM attraction remains unclear. In the current study, electroantennogram (EAG) assays indicated that both OFM and PFM males exhibited a moderate EAG response to Z8-14:Ac and Z10-14:Ac. Rubber septa loaded with varying ratios of Z8-14:Ac (1% to 30%) or Z10-14:Ac (5% to 110%) combined with a constant dose of Z8-12:Ac and E8-12:Ac produced diverse trapping effects. Sex attractants containing Z8-14:Ac did not significantly affect the trapping of PFM males but drastically reduced the capture of OFM males, with the reduction reaching up to 96.54%. Attractants containing more than 10% of Z10-14:Ac simultaneously reduced the number of OFM and PFM males captured. Z8-14:Ac was indispensable for maintaining the specificity of sex pheromones. Fluorescence competitive binding assays of recombinant GmolPBP2 showed the lowest Ki value (0.66 ± 0.02 μM) among the PBPs/GOBPs from OFMs, suggesting that it is the most likely target for Z8-14:Ac. Molecular dynamic simulation and site-directed mutagenesis assays confirmed that the Phe12 residue, which forms a π–alkyl interaction with Z8-14:Ac, was crucial for GmolPBP2 binding to Z8-14:Ac. In conclusion, Z8-14:Ac is vital to the specificity of PFM sex pheromones inhibiting OFM attractants when added to Z8-12:Ac and E8-12:Ac. This could be potentially used to develop species-specific sex attractants for the PFM.

Pull-Out Suture in the Correction of Alar Rim Deformities.

Objectives: This study aimed to investigate the treatment methods used for alar rim problems during the last 5 years and the efficacy of pull-out sutures on the outcomes. Methods: A retrospective study was conducted on patients with alar contour grafting and pull-out suture procedures between 2018 and 2023. Patient records and images, such as retraction or collapse, were evaluated before surgery. The average duration of follow-up after surgery was 26 months, but it may be as long as 5 years. Results: The study enrolled 148 patients, 120 females and 28 males, between the ages of 20 and 44. The distance measured between the alar rim and the long axis of the nostril varied between 3 and 5 mm, with an average value of 3.5 mm. Postoperatively, the exact measurement was performed. However, subjective and objective observational evaluation was preferred for comparison instead of calculating the difference in millimeter due to the minimal change in dimension but significant effects on the outcome. According to patient survey responses, 83.8% of patients (124/148) were satisfied, and 9.5% (14/148) had a moderate response, but 10 cases (6.7%) were not happy with the result. The observational evaluation of the surgeon was very close to the patient's subjective evaluation. We did not have any complications or infections. Conclusion: Postoperative alar retraction may occur due to over-resection of the inner mucosa of the nose or the lower lateral cartilages. Cartilage and mucosal grafts are helpful tools to correct this deformity. Pulling the alar rim's caudal end with a suture prevents the alar mucosa's shrinkage and the alar rim from retracting. The same suture can also help correct retracted alas.

Clinical efficacy of washed microbiota transplantation on metabolic syndrome and metabolic profile of donor outer membrane vesicles.

To clarify the clinical efficacy of washed microbiota transplantation (WMT) for metabolic syndrome (MetS), and explore the differences in the metabolic profile of bacterial outer membrane vesicles (OMVs) in donor fecal bacteria suspension received by MetS patients with good and poor outcomes, and to construct a predictive model for the efficacy of WMT for MetS using differential metabolites. Medical data 65 MetS patients who had completed at least 2 courses of WMT from 2017.05 to 2023.07 were collected. Fecal bacteria suspension of WMT donors were collected, and the clinical data of MetS patients treated with WMT during this period were collected as well. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared. OMVs were isolated from donor fecal bacteria suspension and off-target metabolomic sequencing was performed by Liquid Chromatograph Mass Spectrometer (LC-MS). Compared with baseline, Body mass index (BMI), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) of MetS patients showed significant decreases after the 1st (short-term) and 2nd (medium-term) courses, and fasting blood glucose (FBG) also showed significant decreases after the 1st session. There was a significant difference between the Marked Response OMVs and the Moderate Response OMVs. It was showed that 960 metabolites were significantly up-regulated in Marked Response OMVs and 439 metabolites that were significantly down-regulated. The ROC model suggested that 9-carboxymethoxymethylguanine, AUC = 0.8127, 95% CI [0.6885, 0.9369], was the most potent metabolite predicting the most available metabolite for efficacy. WMT had significant short-term and medium-term clinical efficacy in MetS. There were differences in the structure of metabolites between Marked Response OMVs and Moderate Response OMVs. The level of 9-Carboxy methoxy methylguanine in Marked Response OMVs can be a good predictor of the efficacy of WMT in the treatment of MetS.

C3H7N6]3[B3O5(OH)2] and [C3H8N6]4[B12O19(OH)6]: Two Melamine Borates with Large Birefringence.

The π-conjugated [C3H6+xN6]x+ (x = 0-3) cations are good functional groups, which are widely employed in the preparations of nonlinear optical (NLO) and birefringent materials due to their high hyperpolarizability and optical anisotropy. In this paper, the first melamine hydroxyborate [C3H7N6]3[B3O5(OH)2] (MelBO-I) was synthesized by the boric acid melting method under the molar ratio of H3BO3:C3H6N6 = 1:1. MelBO-I (P21/c) exhibits a two-dimensional (2D) {[C3H7N6]3[B3O5(OH)2]}∞ layer composed of [C3H7N6]+ cations and [B3O5(OH)2]3- anions interconnected via hydrogen bonds. MelBO-I exhibits significant birefringence (Δn = 0.286@546 nm). Under the molar ratio of H3BO3/C3H6N6 = 3:1, [C3H8N6]4[B12O19(OH)6] (MelBO-II) was isolated. In MelBO-II (P21), highly polymerized [B12O19(OH)6]8- groups form a 3D network through hydrogen bonding, featuring 1D tunnels of 8-membered and 16-membered rings filled by [C3H8N6]2+ cations. MelBO-II is the first noncentrosymmetric (NCS) bifunctional melamine borate with a moderate SHG response (0.4 × KDP) and large birefringence (Δn = 0.285@546 nm). The results indicate that incorporating [C3H6+xN6]x+ (x = 0-3) cations into borate can effectively induce birefringence. A high concentration of boric acid promotes the formation of large boric acid cluster anions and facilitates the transformation from the CS to NCS structure.

TMOD-15. TOWARD BRAIN CANCER ORGANOID-INFORMED PRECISION MEDICINE FOR GLIOBLASTOMA

Abstract BACKGROUND Improved preclinical models for glioblastoma are urgently needed to enhance the translation of research to clinical applications. Patient-Derived Tumor Organoids (PDTOs) offer a promising model that can be generated quickly. Here we explored their feasibility. METHODS Primary (n=16) and recurrent (n=2) PDTOs were established using the method described in Jacob et al. Cell. 2020 by dissecting tumours into small fragments, preserving their cytoarchitecture. Histological features of the parent tumour were compared to the matched PDTOs by a neuropathologist. To assess the molecular fidelity, comprehensive whole genome sequencing compared matched tumor tissue, PDTOs, and corresponding normal blood samples (n=11), along with RNA sequencing of matched tumor tissue and PDTOs (n=10). We assessed PDTO responses to regorafenib (n=18) and conventional TMZ (n=9), lomustine (n=9) and 10 Gy of ionizing radiation (IR) (n=6) using the automated imaging system IncuCyte S3® to evaluate whole spheroid brightfield and invasion areas following drug/IR treatment and assess viability. RESULTS We achieved a 100% establishment rate of primary GBMs using same-day procedures and an 80% rate if held under 3 days. Histological features were retained in the PDTO. Molecular overlap was greater than 90%, along with a high concordance in gene expression. PDTOs exhibited notable resistance to temozolomide and lomustine, however, showed a very modest response to IR and a moderate response to regorafenib. IncuCyte S3® analysis revealed discernible changes in whole spheroid brightfield and invasion area for regorafenib-treated PDTOs. Clinically relevant concentrations of regorafenib reduced GBM cell proliferation (Ki67 staining). Beyond this concentration, regorafenib exhibited efficacy in eliminating GBM cells. CONCLUSION PDTOs recapitulate the molecular and histological features of the original tumor and may enable the prediction of individual patient responses to therapies and guide more effective treatment selection. We are now applying our established methodology to assess a new set of promising drug candidates.

Unraveling the landscape of non-melanoma skin cancer through single-cell RNA sequencing technology.

Non-melanoma skin cancer (NMSC) mainly includes basal cell carcinoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma, showing a low mortality rate but the highest incidence worldwide. In recent decades, research has focused on understanding the pathogenesis and clinical treatments of NMSC, leading to significant advances in our knowledge of these diseases and the development of novel therapies, including immunotherapy. Nevertheless, the low to moderate objective response rate, high recurrence, and therapeutic resistance remain persistent challenges, which are partly attributable to the intratumoral heterogeneity. This heterogeneity indicates that tumor cells, immune cells, and stromal cells in the tumor microenvironment can be reshaped to a series of phenotypic and transcriptional cell states that vary in invasiveness and treatment responsiveness. The advent of single-cell RNA sequencing (scRNA-seq) has enabled the comprehensive profiling of gene expression heterogeneity at the single-cell level, which has been applied to NMSC to quantify cell compositions, define states, understand tumor evolution, and discern drug resistance. In this review, we highlight the key findings, with a focus on intratumoral heterogeneity and the mechanism of drug resistance in NMSC, as revealed by scRNA-seq. Furthermore, we propose potential avenues for future research in NMSC using scRNA-seq.

Physiological effects of research handling on the northern elephant seal (Mirounga angustirostris)

Wildlife researchers must balance the need to safely capture and handle their study animals to sample tissues, collect morphological measurements, and attach dataloggers while ensuring their results are not confounded by stress artifacts caused by handling. To determine the physiological effects of research activities including chemical immobilization, transport, instrumentation with biologgers, and overnight holding on a model marine mammal species, we collected hormone, blood chemistry, hematology, and heart rate data from 19 juvenile northern elephant seals (Mirounga angustirostris) throughout a translocation experiment. Across our six sampling timepoints, cortisol and aldosterone data revealed a moderate hormonal stress response to handling accompanied by minor changes in hematocrit and blood glucose, but not ketone bodies or erythrocyte sedimentation rate. We also examined heart rate as a stress indicator and found that interval heart rate, standard deviation of heart rate, and apnea-eupnea cycles were influenced by handling. However, when seals were recaptured after several days at sea, all hormonal and hematological parameters had returned to baseline levels. Furthermore, 100 % of study animals were resighted in the wild post-translocation, with some individuals observed over four years later. Together, these findings suggest that while northern elephant seals exhibit measurable physiological stress in response to handling, they recover rapidly and show no observable long-term deleterious effects, making them a robust species for ecological and physiological research.

The role of leukocyte activation in suspected Non-IgE excipient-related COVID-19 vaccine reactions: An exploratory hypothesis-driven study of pathogenesis.

Background: Adverse allergic reactions due to the administration of vaccines developed for the protection of coronavirus disease 2019 (COVID-19) have been reported since the initiation of the vaccination campaigns in December 15, 2020. Current analyses provided by the Centers for Disease Control and Prevention and the U.S. Food and Drug Administration in the United States have estimated the rates of anaphylactic reactions in 2.5 and 11.1 per million of messenger RNA (mRNA) 1273 and BNT162b2 vaccines administered, respectively. The mechanisms by which these mRNA vaccines induce adverse vaccine reactions have been the subject of conflicting reports. Although skin testing with excipient components found in mRNA-1273 and BNT162b2 vaccines, such as polyethylene glycol (PEG) and related vaccine lipid products, were originally recommended to identify potential predictive biomarkers of adverse allergic reactions, more recent evidence has suggested that routine skin testing with these vaccine excipients have poor predictability and do not correlate with susceptibility to vaccine injury. Objective: The goal of this proof-of-concept (POC) exploratory study was to investigate the role of leukocyte activation (LA) induced by lipid excipients found in mRNA COVID-19 vaccines in the pathogenesis of COVID-19 mRNA vaccine-associated adverse reactions by using an LA assay developed in our laboratory. Results: An LA assay was performed on blood samples obtained from 30 study subjects who were assigned to three study groups: group 1 consisted of 10 subjects who had received an mRNA COVID-19 vaccine and developed a serious vaccine adverse reaction; group 2 consisted of 10 subjects who had received a COVID-19 vaccine and developed a mild adverse reaction; and group 3 consisted of 10 subjects who had not received a COVID-19 vaccine and were asymptomatic. Five excipients were tested in each of the 10 subjects; hence, a potential of 50 reactions could be expressed in each of the three groups. In the subjects in group 1 who had shown clinically severe vaccine effects, 8 of 50 (16%) had severe LA index (LAI) responses (>144.83), 12 of 50 (24%) had moderate LAI responses (87.62 -144.82), and 30 of 50 (60%) had no reaction (0 - 87.61). In the subjects in group 2 who had shown clinically mild vaccine effects, 4 of 50 (8%) had severe LAI responses (>144.83), 9 of 50 (18%) had moderate LAI responses (87.62 -144.82), and 37 of 50 (74%) had no reaction. In the subjects in group 3 who had not received the vaccine and, therefore, had no clinical vaccine effects, 2 of 50 (4%) had severe LAI responses (>144.83), 10 of 50 (20%) had moderate LAI responses (87.62 -144.82), and 38 of 50 (76%) had no reaction LA index (LAI) responses. Conclusion: The results of this exploratory POC study suggest that the measurement of LA induced by PEG and other vaccine-related lipid excipients found in mRNA COVID-19 vaccines may provide a novel and useful predictive biomarker associated with adverse non-immunoglobulin E (IgE) related allergic reactions to these vaccines. The study results also underscore growing concerns related to these non-IgE hypersensitivity reactions and their potential for pathogenesis of adverse vaccine reactions. This is particularly noteworthy because, with the continuing emergence of novel and evolving variants of severe acute respiratory syndrome corona-virus 2 mutants, yearly immunization with mRNA vaccines will most likely be recommended. Although the study was not sufficiently powered to draw definitive conclusions with regard to associations between vaccine-associated COVID-19 reactions and LA, the trends of a more severe set of clinical reactions seen associated with LAI reactivity scores, particularly with ALC-0159 (2-[{polyethylene glycol} 2000]-N,N-ditetradecylacetamide), suggest a potential benefit worthy of exploration in future randomized controlled trials.

Patient Perception of Prolapse Condition Questionnaire: A Validated Patient-Reported Outcome Measure.

Identifying patient-reported outcome measures allows management of urogenital prolapse to be tailored to reflect symptom bother and expectations of treatment. We devised a new single-item questionnaire, the Patient Perception of Prolapse Condition (PPPC), based on the Patient Perception of Bladder Condition (PPBC). The aim was to evaluate the criterion validity, test/re-test reliability and responsiveness of the PPPC. Women attending a tertiary urogynaecology clinic were recruited. At visit 1, patients completed the Prolapse Quality of Life (P-QOL) and PPPC questionnaires, and underwent a Pelvic Organ Prolapse Quantification (POP-Q) examination. This allowed assessment of criterion validity using Spearman's rank correlation (rho) of the PPPC against validated subjective and objective outcomes. At visit 2, within the next 6weeks, PPPC was repeated to assess test/re-test reliability using Cronbach's alpha (α). In those undergoing pelvic floor surgery, responsiveness of the PPPC was assessed at visit 3 by correlating PPPC and P-QOL scores 6weeks post-operatively. A total of 178 patients attended visit 1, 60 attended visit 2 and 58 attended visit 3. At visit 1, there were moderate correlations between the PPPC and both objective (POP-Q: rho = 0.385, p < 0.01, CI 0.192-0.549) and subjective (P-QOL: rho = 0.635, p < 0.01, CI 0.493-0.744) measures confirming criterion validity. Test/re-test reliability was high (α = 0.89). Correlation with post-operative PPPC and P-QOL confirmed moderate responsiveness (rho = 0.54, p < 0.01). The PPPC, a novel single-item patient-reported measure of prolapse condition, demonstrated good criterion validity, test/re-test reliability and responsiveness. These findings support the use of the PPPC as a global assessment of prolapse condition.

Measurement properties of the Brazilian-Portuguese version of the PROMIS-29 questionnaire and the Impact Score in patients with chronic low back pain

BackgroundA task force from the US National Institute of Health aimed to establish parameters for surveys with patients with chronic low back pain (LBP) by recommending the use of the Patient-Reported Outcome Measurement Information System 29-item (PROMIS-29) questionnaire and the stratification according to the Impact Score. We aimed to assess the internal consistency, reliability, measurement error, construct validity and responsiveness of the Brazilian-Portuguese version of the PROMIS-29 questionnaire (version 2.1) and the Impact Score in patients with chronic LBP.MethodsA prospective cohort study was carried out with patients with chronic LBP who were receiving physiotherapy treatment in clinics in São Paulo and Vitória cities, Brazil. The sample included 102 patients with chronic LBP, aged between 18 and 80 years, and with the ability to read and write in the Brazilian-Portuguese language. Exclusion criteria were patients with serious spinal conditions, cognitive impairment, pregnant women, and patients who had undergone lumbar surgery within the past six months. The PROMIS-29 questionnaire, the 12-item Short-Form Health Survey and the Roland-Morris Disability Questionnaire were applied. The PROMIS-29 questionnaire was reapplied after 24 hours and 4 weeks.ResultsThe PROMIS-29 questionnaire showed Cronbach’s Alpha values between 0.81 (anxiety) and 0.91 (depression). The ICC2.1 ranged from 0.85 (95% CI: 0.77 to 0.89) to 0,97 (CI 95%: 0.95 to 0.98). The SEM values ranged between 0.85 (physical function) and 2.62 (ability to participate in social roles and activities). The Impact Score showed Cronbach’s Alpha, ICC2.1 and SEM values of 0.91, 0.97 (95% CI: 0.95 to 0.98) and 0.56, respectively. The PROMIS-29 questionnaire and the Impact Score showed sufficient construct validity. The PROMIS-29 questionnaire showed moderate responsiveness, while the Impact Score showed sufficient responsiveness.ConclusionsBoth the Brazilian-Portuguese version of the PROMIS-29 questionnaire and the Impact Score showed sufficient internal consistency, reliability, construct validity and responsiveness in Brazilian patients with chronic LBP. The results support the US National Institutes of Health’s recommendation to use the PROMIS-29 questionnaire and the Impact Score in patients with chronic LBP. We suggest that future studies evaluate the structural validity of the Brazilian-Portuguese version of the PROMIS-29 questionnaire.Clinical trial numberNot applicable.

Responsiveness of the P4, Patient Specific Functional Scale 2.0, Satisfaction and Recovery Index, and SF-12 in Patients With Musculoskeletal Disorders.

Background Recently, estimation of intervention effects has been recommended using minimum important change (MIC). This study aimed to investigate the responsiveness of the four-item pain intensity measure (P4), Patient Specific Functional Scale 2.0 (PSFS 2.0), Satisfaction and Recovery Index (SRI), and physical (PCS) and mental component summary (MCS) scores of the SF-12v2® Health Survey Acute (QualityMetric Inc. & Fukuhara S, Kyoto) in patients with musculoskeletal disorders and to estimate their MICs. Methodology Data of outpatients receiving musculoskeletal physical therapy were collected using a survey in multi-center cohorts. The participants completed the first survey before their first physical therapy session and the second survey after the third to seventh sessions. Responsiveness was assessed by investigating the area under the receiver operating characteristic curve (AUC) and by investigating prior hypotheses with correlations between change scores. In the former method, the AUCs of the measures were calculated for discriminating improved cases (i.e., 11-point Global Rating of Change Scale (GRCS) ≥ 2) and non-improved cases (i.e., GRCS < 2). The MIC scores were estimated with GRCS using the predictive modeling method. Results Data from 100 participants were analyzed. The PSFS 2.0 satisfied both acceptable responsiveness criteria, the P4 and SRI satisfied the moderate responsiveness criterion of the construct approach only, and the PCS and MCS satisfied both poor responsiveness criteria. The MICs were 1.64, 2.92, 6.16, 4.49, and 1.67 for the P4, PSFS 2.0, SRI, and PCS and MCS scores, respectively. Conclusion The PSFS 2.0 has acceptable responsiveness and can be used to determine treatment effects in clinical practice, while the P4 and SRI can also be used in some cases.

Long-term outcomes of intravenous corticosteroid pulse therapy for rapidly progressive alopecia areata: A single-center retrospective analysis of 106 cases and usefulness evaluation of a scoring system originally designed for half-year efficacy prediction for extended periods.

Intravenous corticosteroid pulse therapy (IVPT) has been preferentially conducted for rapidly progressive alopecia areata (RP-AA); however, the evaluation of long-term outcomes has been insufficient. In this study, 106 IVPT-treated RP-AA patients (36 males and 70 females) who were followed up for more than 1 year and up to 6.8 years were retrospectively analyzed. The mean observation period was 1137.8 ± 587.9 days (range 380-2490). The mean severity of alopecia tool (SALT) score before IVPT was 21.3 ± 23.4 but whole-scalp hair loss was observed in all cases after the intervention, suggesting that IVPT was performed soon after the onset. With additional interventions represented by intralesional triamcinolone acetonide injection with or without topical potent corticosteroid for those who insufficiently responded at 6 months after IVPT, 64.2%, 14.2%, and 21.7% of the patients respectively achieved good response (GR; SALT score ≤25), moderate response (MR; 25 < SALT score <75), and poor response (PR; 75 ≤ SALT score) 1 year after IVPT. On the final evaluation, the proportions of patients with GR, MR, and PR were 79 (74.5%), 7 (6.6%), and 20 (18.9%). Sixteen patients achieved and maintained full hair regrowth with IVPT alone until the end of observation. A previously reported scoring system for the short-term outcome prediction was shown to be useful for distinguishing the final-point GR responders from PR responders (P = 0.003). Of note, 21 patients were found to have some symptoms suggestive of the existence of preceding infectious diseases and tended to relapse. The revised scoring system adding the absence of preceding infectious diseases as one factor successfully predicted the occurrence of the relapse in our cohort (P = 0.002). Taken together, previously unreported real-world efficacy of IVPT to RP-AA was elucidated with the invention of a tool putatively enabling optimal long-term management.

A-270 Evaluation of a multiplex panel to determine antibody profile to monkeypox virus in vaccinated, exposed, and naïve individuals

Abstract Background Monkeypox Virus (MPXV) is a double-stranded DNA virus of the Orthopoxvirus genus that causes Mpox disease with symptoms such as swollen lymph nodes, chills, exhaustion, and blisters that appear on the face, inside the mouth, hands, feet etc. The genus orthopoxvirus (OPXV) has four species, namely, MPXV, smallpox-causing variola major virus (VARV), variola minor virus, and cowpox virus (CPXV), that cause disease in humans. In 1980, the World Health Assembly declared that smallpox had been eradicated due to a successful global vaccination program. This vaccine also provided cross-protection against other OPXV. Historically, the pox disease was rarely seen outside West and Central Africa. The first case of Mpox was identified in 1970 in a 9-year-old boy from the Democratic Republic of Congo (DRC), two years after the smallpox vaccination was discontinued. Since then, it has been reported in 11 African countries. In 2003, the first Mpox outbreak outside of Africa was in the USA and was linked to contact with infected pet prairie dogs. The recent 2022-2023 Mpox outbreak has generated renewed interest in the scientific community to understand the level of OPXV-specific immunity in the various geographic regions, among different age groups, and especially in the risk groups and its impact on future outbreaks by using integrated serosurveillance. To meet the need of the hour, we developed a novel multiplex assay for the detection of human IgG antibodies using Luminex® xMAP® technology for the detection of the human IgG profiles. Methods We have evaluated 11 different recombinant antigens from VARV, Vaccinia virus (VACV), and MPXV in a multiplex assay for detecting human IgG antibodies to OPXV using Luminex® xMAP® technology. We have covalently coupled magnetic fluorescent microspheres to three recombinant proteins from VARV, three from VACV, and five from MPXV to interrogate IgG responses. This 15-plex assay also includes four internal controls that assure the assay and reagent performance. In this preliminary evaluation, we have tested 84 de-identified serum and plasma from healthy subjects. We evaluated 24 serum samples of MPXV-exposed individuals procured commercially. We performed principal component analysis to determine which of these 11 antigens contributed the maximum differential and a result analysis algorithm was developed to predict these individuals' positive and negative antibody outcomes. Results The healthy subjects that were assumed to have been vaccinated showed positive response to A35R of MPXV; A36R of VARV, A33R of VACV, the homologous proteins in the three species and were distinct from unvaccinated younger individuals. There was some reactivity with B6R of MPXV protein. In MPXV-exposed subjects, we observed strong positive antibody responses to A35R of MPXV, A36R of VARV, A33R of VACV, and B6R of MPXV proteins in 19 out of 24 individuals. Fifteen individuals showed a moderate positive response to the A27L protein of VACV, and 8 out of 24 showed a weak positive response to the A29 protein of MPXV. Conclusions This panel is a useful tool to understand the level of OPXV-specific immunity by measuring IgG profiles for successful serosurveillance programs for public health.

Unlocking The Potential Of Natural Polymers: A Comparative Study For Innovative Drug Delivery Systems

This study aims to characterize and compare four biopolymers - pectin, guar gum, xanthan gum, and sodium alginate - for their potential use in drug delivery systems by evaluating their hydrophilicity, pH sensitivity, and thermosensitivity. Biopolymer films were prepared and subjected to water absorption tests for hydrophilicity, gravimetric analysis in varying pH conditions for pH sensitivity, and weight change measurements after heat exposure for thermosensitivity. Each test was conducted in five trials to ensure reliability. Pectin demonstrated the highest responsiveness across all tests, showing rapid water absorption (6.46 seconds), significant pH sensitivity (0.53g weight change in acidic conditions), and high thermosensitivity (0.378g weight change). Guar gum showed moderate responsiveness, while xanthan gum and sodium alginate exhibited the most stability across varying conditions. Pectin's high responsiveness suggests suitability for smart, multi-stimuli-responsive systems. Guar gum's moderate responsiveness indicates potential for controlled release formulations. The stability of xanthan gum and sodium alginate makes them ideal for applications requiring consistent drug release in diverse physiological environments. This study offers a comprehensive, comparative analysis of four widely used biopolymers, filling a gap in the existing literature. The results provide a foundation for developing tailored, sustainable drug delivery systems, contributing to the advancement of personalized medicine and environmentally friendly pharmaceutical practices

Sleeve-gastrectomy results in improved metabolism and a massive stress response of the liver proteome in a mouse model of metabolic dysfunction-associated steatohepatitis

BackgroundBariatric surgery has been shown to improve the histopathological findings in patients with obesity and metabolic dysfunction-associated steatohepatitis, but there are also reports about non-responders or progressive disease after bariatric interventions. Therefore, it is of utmost importance to understand the pathophysiological processes in the liver after bariatric surgery. Materials and methodsIn the present study, 4 weeks old male C57/Bl6 mice were fed a Western Diet to induce metabolic dysfunction-associated steatohepatitis and sleeve-gastrectomy (SG), or sham operation in the pair-fed and ad libitum control group were performed. Mice were observed for two or eight weeks after surgery and metabolic assessment was performed throughout the experiment. Histopathology, flow cytometry and proteomic analyses were conducted to evaluate hepatic inflammation, liver metabolism and affected signaling pathways. ResultsWeight loss was higher, and metabolism significantly improved after SG. Two weeks after SG major inflammatory and regulatory disturbances in the liver were observed. The proportion of hepatic CD3+NK1.1+ cells were decreased, and proteins involved in apoptosis like Fas, Casp1 and Casp9 or in the acute phase response were upregulated in SG mice. These disturbances decreased in the long-term and we observed an increase of many proteins involved in lipid metabolism eight weeks following SG. ConclusionsThe rapid weight loss and decrease of hepatic fat after SG lead to a proinflammatory response in the liver in the early phase after surgery, which changes to a more moderate immune response in the long-term. We suggest a preoperative risk stratification and postoperative surveillance depending on the histopathological findings.

Muscarinic receptor drug trihexyphenidyl can alter growth of mesenchymal glioblastoma in vivo.

Glioblastoma (GBM) is the most commonly occurring and most aggressive primary brain tumor. Transcriptomics-based tumor subtype classification has established the mesenchymal lineage of GBM (MES-GBM) as cancers with particular aggressive behavior and high levels of therapy resistance. Previously it was show that Trihexyphenidyl (THP), a market approved M1 muscarinic receptor-targeting oral drug can suppress proliferation and survival of GBM stem cells from the classical transcriptomic subtype. In a series of in vitro experiments, this study confirms the therapeutic potential of THP, by effectively suppressing the growth, proliferation and survival of MES-GBM cells with limited effects on non-tumor cells. Transcriptomic profiling of treated cancer cells identified genes and associated metabolic signaling pathways as possible underlying molecular mechanisms responsible for THP-induced effects. In vivo trials of THP in immunocompromised mice carry orthotopic MES-GBMs showed moderate response to the drug. This study further highlights the potential of THP repurposing as an anti-cancer treatment regimen but mode of action and d optimal treatment procedures for in vivo regimens need to be investigated further.

Neurophysiological response to social feedback in stressful situations.

The relationship between external feedback and cognitive and neurophysiological performance has been extensively investigated in social neuroscience. However, few studies have considered the role of positive and negative external social feedback on electroencephalographic (EEG) and moderate stress response. Twenty-six healthy adults underwent a moderately stressful job interview consisting of a modified version of the Trier Social Stress Test. After each preparation, feedback was provided by an external committee, ranging from positive to negative with increasing impact on subjects. Stress response was measured by analysing response times (RTs) during the speech phase, while cognitive performance was assessed using a Stroop-like task before and after the test. Results indicate that RTs used to deliver the final speeches with negative feedback were significantly lower compared with those used for the initial speech with positive feedback. Moreover, a generalized improvement in Stroop-like task performance was observed in the post-SST compared with the pre-SST. Consistent with behavioural results, EEG data indicated greater delta, theta, and alpha band responses in right prefrontal and left central areas, and for delta and theta bands, also in parietal areas in response to positive feedback compared with aversive-neutral feedback, highlighting greater cognitive effort required by the former. Conversely, an increase in these bands in right and left temporal and left occipital areas was observed following negative and aversive feedback, indicative of an adaptive response to stress and emotion-regulatory processes. These findings suggest that negative social feedback in moderately stressful and noncritical conditions could contribute to improving individual cognitive performance.

Consequences of the perivascular niche remodeling for tumoricidal T-cell trafficking into metastasis of ovarian cancer.

The treatment-induced activation level within the perivascular tumor microenvironment (TME) that supports T-cell trafficking and optimal T-cell differentiation is unknown. We investigated the mechanisms by which inflammatory responses generated by tumor-specific T cells delivered to ovarian tumor-bearing mice alone or after oncolytic vaccinia virus-driven immunogenic cancer cell death affect antitumor efficacy. Analyses of the perivascular TME by spatially resolved omics technologies revealed reduced immunosuppression and increased tumoricidal T-cell trafficking and function after moderate inflammatory responses driven by a CXCR4 antagonist-armed oncolytic virus. Neither weak nor high inflammation created a permissive TME for T-cell trafficking. Notably, treatment-mediated differences in T-cell effector programs acquired within the perivascular TME contrasted with comparable antigenic priming in the tumor-draining lymph nodes regardless of the activation mode of antigen-presenting cells. These findings provide new insights into combinatorial treatment strategies that enable tumor-specific T cells to overcome multiple barriers for enhanced trafficking and control of tumor growth. .