Shift In Proportion Research Articles

P-697. Increases in Ages and Bacterial Coinfection in Hospitalized Children with Respiratory Syncytial Virus Infection in Taiwan:2019- 2023

Abstract Background Efforts to expand RSV epidemiological data are crucial, especially considering upcoming interventions such as long-acting monoclonal RSV-neutralizing antibodies and maternal vaccines for RSV prevention, which have the potential to alter the landscape. Methods A retrospective study was conducted at Chang Gung Memorial Hospital, analyzing children hospitalized with RSV infection before, during and after the COVID-19 pandemics from 2019 to 2023. Clinical data were collected and stratified by year for analysis. Plasma microbial free-DNA sequencing (mcfDNA) was performed on selected cases with C-reactive protein > 100 mg/L to enhance diagnostic yields. Results A total of 997 children hospitalized for RSV infection was enrolled. In 2019, 2022, and 2023, the incidence of RSV-related hospitalization among children aged 0-4 years remained relatively stable, ranging between 600-700 per 100,000. However, in 2020 during a strict national nonpharmaceutical intervention, there was a notable spike, doubling to reach a peak, followed by an 80% decrease in 2021. In age subgroup analyses comparing 2022 and 2023 to 2019, the incidence of RSV-related hospitalization among children aged < 2 years gradually decreased from 1576 per 100,000 in 2019 to 1212 per 100,000 in 2022 (P=0.03) and 1262 per 100,000 (P=0.07) in 2023. Conversely, the incidence of RSV-related hospitalization among children aged 2-4 years significantly increased from 124 per 100,000 in 2019 to 347 per 100,000 in 2022 (P< 0.001) and 419 per 100,000 in 2023 (P< 0.001). Independent risk factors for CRP >100 mg/L in RSV cases were year 2023 (aOR:4.03, P=0.008) and age 2-4 years (aOR:3.33, P< 0.001). In 2023, among 23 children with CRP >100 mg/L, Hemophilus influenzae was identified in two children receiving bronchoalveolar lavage, and in 73% (11/15) of samples underwent plasma mcfDNA. Conclusion Following the COVID-19 pandemic, there was a proportional shift in RSV cases towards children over 2 years of age. Increase in age exhibited a higher rate of bacterial infections, particularly with Haemophilus influenzae. These findings offer critical implication for RSV prevention strategies and treatment of community-acquired pneumonia. Disclosures All Authors: No reported disclosures

Oxygenation and intestinal perfusion and its association with perturbations of the early life gut microbiota composition of children with congenital heart disease.

Early life gut microbiota is known to shape the immune system and has a crucial role in immune homeostasis. Only little is known about composition and dynamics of the intestinal microbiota in infants with congenital heart disease (CHD) and potential influencing factors. We evaluated the intestinal microbial composition of neonates with CHD (n = 13) compared to healthy controls (HC, n = 30). Fecal samples were analyzed by shotgun metagenomics. Different approaches of statistical modeling were applied to assess the impact of influencing factors on variation in species composition. Unsupervised hierarchical clustering of the microbial composition of neonates with CHD was used to detect associations of distinct clusters with intestinal tissue oxygenation and perfusion parameters, obtained by the "oxygen to see" (O2C) method. Overall, neonates with CHD showed an intestinal core microbiota dominated by the genera Enterococcus (27%) and Staphylococcus (20%). Furthermore, a lower abundance of the genera Bacteroides (8% vs. 14%), Parabacteroides (1% vs. 3%), Bifidobacterium (4% vs. 12%), and Escherichia (8% vs. 23%) was observed in CHD compared to HCs. CHD patients that were born by vaginal delivery showed a lower fraction of the genera Bacteroides (15% vs. 21%) and Bifidobacterium (7% vs. 22%) compared to HCs and in those born by cesarean section, these genera were not found at all. In infants with CHD, we found a significant impact of oxygen saturation (SpO2) on relative abundances of the intestinal core microbiota by multivariate analysis of variance (F[8,2] = 24.9, p = 0.04). Statistical modeling suggested a large proportional shift from a microbiota dominated by the genus Streptococcus (50%) in conditions with low SpO2 towards the genus Enterococcus (61%) in conditions with high SpO2. We identified three distinct compositional microbial clusters, corresponding neonates differed significantly in intestinal blood flow and global gut perfusion. Early life differences in gut microbiota of CHD neonates versus HCs are possibly linked to oxygen levels. Delivery method may affect microbiota stability. However, further studies are needed to assess the effect of potential interventions including probiotics or fecal transplants on early life microbiota perturbations in neonates with CHD.

Unique lymphocyte transcriptomic profiles in septic patients with chronic critical illness.

Despite continued improvement in post-sepsis survival, long term morbidity and mortality remain high. Chronic critical illness (CCI), defined as persistent inflammation and organ injury requiring prolonged intensive care, is a harbinger of poor long-term outcomes in sepsis survivors. Current dogma states that sepsis survivors are immunosuppressed, particularly in CCI. Investigation of this immune suppression in heterogeneous immune populations across distinct clinical trajectories and outcomes, along with limited sampling access, is accessible via single-cell RNA sequencing (scRNA-seq). scRNA-seq analysis was performed on healthy subjects (n=12), acutely septic patients at day 4 ± 1 (n=4), and those defined as rapid recovery (n=4) or CCI (n=5) at day 14-21. Differential gene expression and pathway analyses were performed on peripheral blood lymphocytes at both a population and annotated cell subset level. Cellular function was assessed via enzyme-linked immunosorbent spot (ELISpot), cytokine production analysis, and T-cell proliferation assays on an additional cohort of septic patients (19 healthy, 68 acutely septic, 27 rapid recovery and 20 classified as CCI 14-21 days after sepsis onset). Sepsis survivors that developed CCI exhibited proportional shifts within lymphoid cell populations, with expanded frequency of CD8+ and NK cells. Differential expression and pathway analyses revealed continued activation in T cells and NK cells, with generalized suppression of B-cell function. Both T and NK cell subsets displayed transcriptomic profiles of exhaustion and immunosuppression in CCI, particularly in CD8+ T effector memory (TEM) cells and NK cells. Functional validation of T-cell behavior in an independent cohort demonstrated T cells maintained proliferative responses in vitro yet exhibited a marked loss of cytokine production. IFN-γ production at the acute phase (day 4 ± 1) was significantly reduced in subjects later classified as CCI. Sepsis patients exhibit unique T-, B-, and NK-cell transcriptional patterns that are both time- and clinical trajectory-dependent. These transcriptomic and pathway differences in sepsis patients that develop CCI are associated with exhaustion in CD8+ TEM cells and NK cells. Understanding the specific immune system patterns of different cell subsets after sepsis at a molecular level will be key to the development of personalized immunotherapy and drug-targeting intervention. https://clinicaltrials.gov/, identifier NCT02276417.

Prognostic value of residual disease (RD) biology and gene expression changes during the neoadjuvant treatment in patients with HER2-positive early breast cancer (EBC).

In human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), we investigated tumor and immune changes during neoadjuvant treatment and their impact on residual disease (RD) biology and prognostic implications across four neoadjuvant studies of trastuzumab with or without lapatinib, and with or without chemotherapy: CALGB 40601, PAMELA, NeoALTTO, and NSABP B-41. We compared tumor and immune gene expression changes during neoadjuvant treatment and their association with event-free survival (EFS) by uni- and multivariable Cox regression models in different cohorts and timepoints: 452 RD samples at baseline including 169 with a paired RD, and biomarker changes during neoadjuvant therapy, evaluating model performance via the c-index. Analysis of 169 paired tumor samples revealed a shift in intrinsic subtype proportions from HER2-enriched at baseline (50.3%) to normal-like (49.1%) followed by luminal A (18.9%) in RD. This luminal phenotypic change was supported by decreased correlation to the HER2-enriched centroid, ERBB2, and HER2 amplicon genes and increased correlation to the luminal A centroid (Wilcoxon test P < 0.001). Additionally, RD showed relative immune activation marked by significant increases in B-cell, CD8 T-cell, and natural killer cell signatures (Wilcoxon test P < 0.05). In multivariable Cox models, intrinsic subtypes at baseline provided more prognostic information, while immune gene expression signatures provided more prognostic information in RD. Notably, the best multivariable EFS model (c-index= 0.77) integrated the immunoglobulin G signature from RD samples (adjusted hazard ratio 0.45, 95% confidence interval 0.30-0.67, adjusted P= 0.002). In patients with HER2-positive EBC and RD, tumor biomarkers provide more prognostic information at baseline. In contrast, immune biomarkers perform better for EFS prognosis in RD.

Comprehensive single-cell aging atlas of healthy mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer

Aging is the greatest risk factor for breast cancer; however, how age-related cellular and molecular events impact cancer initiation is unknown. In this study, we investigated how aging rewires transcriptomic and epigenomic programs of mouse mammary glands at single-cell resolution, yielding a comprehensive resource for aging and cancer biology. Aged epithelial cells exhibit epigenetic and transcriptional changes in metabolic, pro-inflammatory and cancer-associated genes. Aged stromal cells downregulate fibroblast marker genes and upregulate markers of senescence and cancer-associated fibroblasts. Among immune cells, distinct T cell subsets (Gzmk+, memory CD4+, γδ) and M2-like macrophages expand with age. Spatial transcriptomics reveals co-localization of aged immune and epithelial cells in situ. Lastly, we found transcriptional signatures of aging mammary cells in human breast tumors, suggesting possible links between aging and cancer. Together, these data uncover that epithelial, immune and stromal cells shift in proportions and cell identity, potentially impacting cell plasticity, aged microenvironment and neoplasia risk.

Longitudinal analyses of infants’ microbiome and metabolome reveal microbes and metabolites with seemingly coordinated dynamics

Population studies have shown that the infant’s microbiome and metabolome undergo significant changes in early childhood. However, no previous study has investigated how diverse these changes are across subjects and whether the subject-specific dynamics of some microbes correlate with the over-time dynamics of specific metabolites. Using mixed-effects models, and data from the ABC study, we investigated the early childhood dynamics of fecal microbiome and metabolome and identified 83 amplicon sequence variants (ASVs) and 753 metabolites with seemingly coordinated trajectories. Enrichment analysis of these microbes and molecules revealed eight ASV families and 23 metabolite groups involving 1032 ASV-metabolite pairs with their presence-absence changing in a coordinated fashion. Members of the Lachnospiraceae (464/1032) and metabolites related to cholestane steroids (309/1032) dominated proportional shifts within the fecal microbiome and metabolome as infants aged.

Spatiotemporally weighted regression (STWR) for assessing Lyme disease and landscape fragmentation dynamics in Connecticut towns

Understanding the landscape determinants that escalate Lyme disease (LD) risk through various times and regions is vital for appraising disease susceptibility and shaping precise intervention and prevention strategies. This research introduces a novel data-driven framework to identify potential indicators from an extensive array of potential variables. We then deployed an advanced spatiotemporal weighted regression (STWR) model to investigate how landscape fragmentation metrics correlate with the spatiotemporal variability of LD incidence rate in Connecticut towns. We proposed a data-driven filtering framework to select five variables from a large data pool. The analysis unveils that LD incidence rates exhibit heightened sensitivity to proportional or exponential shifts in landscape fragmentation; logarithmic and squared transformations of landscape metrics shed light on lesser effects and venue for potential parabolic relationships. Observations also disclose significant spatial trends, showing elevated LD incidence rates in locales with vast, uninterrupted deciduous forests, alongside contributions from wetland ecosystem-related variables to the rise in disease occurrence. Compared with Geographically Weighted Regression (GWR), the STWR model proved more potent and reliable with higher R2 and lower estimated standard errors (SE). The STWR model is highly flexible in terms of spatiotemporal variations in data. The STWR results further reversely indicate the changes made by the Center for Disease and Prevention (CDC) in the case classification of LD in 2008. The integration of data-driven and model-driven approaches in this study delivers a robust framework that combines empirical pattern detection with theoretical insight, enhancing the robustness and predictive power of ecological studies.

Pemetaan Potensi Ekonomi dalam Upaya Meningkatkan Penyerapan Tenaga Kerja di Kota Surabaya

The purpose of this study is to analyze the economic potential in order to increase employment in the city of Surabaya. Compilation of mapping analysis of economic potential in employment in Surabaya will use two basic research designs, namely Exploratory and Descriptive Research which is carried out in stages. From the results of the calculation of the Location Quotient index (base and non basis), the Differential Shift component (internal growth component), and the Proportional Shift component (external growth component) as well as the sectoral typology of economic sectors explains that there are three potential sectors in the Surabaya City area namely: Transportation Sector, Accommodation Provision Sector, and Information Sector. While the economic sector according to the business field, the highest economic growth was achieved by the business of the Provision of Accommodation and Food and Drink followed by the growing Information and Communication business field and finally the Construction business field

A New Technology for Industrial Strain Mapping Using Single-Wall Carbon Nanotube Sensors

Measurements of mechanical strain are widely used in heavy industry to design and test new structures and to ensure the safety of installed infrastructure. However, the few practical methods for strain measurement all have serious limitations. To complement these methods, we have developed a new strain technology, called S4 for “strain-sensing smart skin,” which uses single-wall carbon nanotubes (SWCNTs) as microscopic sensors. Nanotubes dilutely embedded in a polymer are applied as a thin film to specimen surfaces of interest. Subsequent strains in the specimen are transmitted by load transfer through the film to the nanotubes, inducing axial compression or extension. Those small structural deformations of the SWCNTs alter the semiconducting band gaps in predictable ways, causing proportional shifts in the peak wavelengths of their near-infrared fluorescence emission. Shifts are quantified by optically exciting the specimen surface and spectrally analyzing the resulting fluorescence to deduce strain values at the probed locations. The S4 method has recently been implemented using hyperspectral imaging. We demonstrate measurements in less than one minute of strain maps containing hundreds of thousands of pixels with 50 microstrain noise levels and 0.2 mm spatial resolution. This technology has promising potential to become a large-scale commercialized application of carbon nanotechnology.

Outcome of Midwife-Led Debriefing on Postpartum Depression in Western Region, Kenya

ABSTRACT Context: Giving birth is a traumatic experience for women, and if unresolved, the emotions it causes can have a lasting negative impact on mental health, including depression in the postpartum period. Depression is a prevalent mental illness that can have major repercussions, particularly after giving birth. There is evidence of postpartum depression. However, many studies have concentrated on the prevalence of postpartum depression. In middle-income countries, including Kenya, very few studies have assessed the outcome of midwife-led debriefing for the prevention of postpartum depression. Aim: The study aimed to assess the outcome of a midwife-led debriefing on postpartum depression in the Western region of Kenya. Methods: The study was a quasi-experimental design with pre and post-test assessments. The study used the postnatal register as the sampling frame. Systematic random sampling was used to identify and allocate participants to the study's intervention and control groups. The target population was women of childbearing age. The study participants were women who gave birth during the study period, of which a sample of 212 participated in the study. The 165 participants were allocated to the intervention group, while 47 participants were in the control group, based on the 22% Prevalence of Postpartum Depression (PPD). Data was collected using a structured questionnaire on demographic characteristics and the Edinburg Postpartum Depression Scale (EPDS) for assessment of postpartum depression level. Results: The study results show that midwife-led debriefing significantly reduced the symptoms of postpartum depression (t=14.672, p-value=0.003). The Odds ratio (OR= 5.41) indicated an association between the intervention of midwife-led debriefing and the outcome (Reduced symptoms of depression) as compared with the standard care. The coefficient of β=0.871 shows a proportional shift in postpartum depression prevention of 0.871 units for every unit increase in midwife-led debriefing. At the 5% significance level, the null hypothesis was rejected (p=0.003), suggesting that postpartum depression could potentially be prevented using midwife-led debriefing. Conclusion: Midwife-led debriefing reduces postpartum depression symptoms. The study recommends that the national and county government health systems integrate midwife-led debriefing into the standard practice for postpartum care.

Baking quality of wheat variety mixtures: Describing the mechanisms for mixture effects

The use of intra-crop diversity (e.g.: variety mixtures) in bread wheat cropping is getting popular in Europe, mostly for agronomic purposes. However, much less is known about the implications on baking quality.In this paper, we formalized and tested a framework based on two hypothetical mechanisms for mixture effects as a result of plant interactions within mixtures: (i) proportion shifts, relating to changes in grain weight proportion of the varieties at harvest and (ii) component alteration, relating to changes in the baking quality of the component varieties. To test this framework, we measured several baking quality indicators on twelve variety mixtures and their component varieties in pure stands. By recording varietal proportions at harvest, we could measure the relative importance of both mechanisms in explaining observed mixture effects.Our results showed that proportion shifts explained a large share of mixture effects on protein baking quality (Zélény sedimentation index and W baking strength) but failed to explain mixture effects on protein content in one year and Hagberg's falling number in both years. Our results also suggest component alteration on protein content resulting from altered nitrogen uptake in mixtures, and possibly on Hagberg's falling number resulting from lodging reduction in mixtures.

High throughput Targeted Transcriptome Sequencing of Bone Marrow Mononuclear Cells identifies a Rare Leukemia-Specific T Cell Subset.

Abstract Many applications of scRNA-seq are focused on cell type identification, gene regulatory networks, or biomarker discovery. These applications often do not require surveying the whole transcriptome (WT), but rather require the interrogation of specific sets of well-characterized genes. In these cases, sequencing the entire transcriptome may be adding unnecessary costs. To increase throughput and minimize sequencing costs, the development of a targeted gene enrichment method is required. Here, we demonstrate an approach to combine split-pool combinatorial barcoding with enrichment of 1000 genes (Immune1000 panel) representing immune cell markers and pathways. We use this gene panel to characterize 730,000 human bone marrow mononuclear cells (BMMCs) from four leukemia and four healthy donors. We found that enrichment with the Immune1000 Panel enabled the characterization of all major immune cell types at low sequencing depth and allowed for the detection of known leukemia-associated shifts in cell type proportions. Moreover, our targeted sequencing method enabled the detection of a rare (~0.35%), leukemia-specific T cell population that showed highly proliferative and cytotoxic potential. Overall, we demonstrate our modular enrichment strategy preserves biological structure and allows for deep characterization of rare disease-relevant cell types and gene signatures with less sequencing.

Changes in Cellular Morphology in Bronchoalveolar Lavage Fluid of Children with Mycoplasma Pneumoniae Pneumonia

Objective To study changes of cell morphology in BALF in children with Mycoplasma pneumoniae pneumonia (MPP). Methods From December 2021 to May 2022, a group of 32 children diagnosed with Acute MPP and admitted for treatment in the Pediatrics Department and PICU of the First Affiliated Hospital of Xinxiang Medical University were selected for our study. These patients underwent bronchoalveolar lavage as part of their clinical assessment. For comparison, we included a control group comprising 10 children who were not infected but had bronchial foreign bodies. We investigated the cellular composition in the bronchoalveolar lavage fluid (BALF) using Wright-Giemsa staining and microscopic evaluation, aiming to understand the relationship between shifts in cell proportions and extra-pulmonary symptoms associated with MPP. Results In this study, a total of 42 cases were enrolled, with 32 cases in the study group and 10 cases in the control group. There were no statistically significant differences in gender, age, height, weight, and BMI between the two groups (p &gt; 0.05). The study group exhibited significantly higher levels of neutrophil percentage (GRA%), CRP, D-dimer, and LDH in blood routine tests compared to the control group (p &lt; 0.05). Furthermore, the proportions of neutrophils (%) and macrophages (%) in BALF were significantly higher in the study group compared to the control group (p&lt; 0.05), while the proportion of lymphocytes (%) in BALF showed no statistically significant difference between the two groups (p&gt; 0.05). Conclusion In the acute phase of MPP in children, BALF is predominantly composed of neutrophils. A lower proportion of lymphocytes in BALF is associated with a higher incidence of extra-pulmonary manifestations and longer hospitalization duration.

Abstract SY38-02: Clinical investigations of obesity in cancer: BMI and other confounders

Abstract SY38-02: Clinical investigations of obesity in cancer: BMI and other confounders

Analisis Potensi Perikanan Tangkap di Kabupaten Ngada dalam Meningkatkan Kesejahteraan Masyarakat

This study aims to find out how the potential for capture fisheries in Ngada Regency. This research uses quantitative research methods. Data collection through written information about an object, subject or event in the form of archives or documents at the Ngada District Fisheries Service. With the Shift Share analysis technique which is a technique for analyzing changes in the structure of the regional economy with the national (Provincial) economy.&#x0D; The results of this study indicate that the capture fisheries potential in Ngada Regency in 2016-2022 which is calculated using Shift Share analysis, shows: the National Share component, the regional capture fisheries potential of Ngada Regency is positive; the Proportional Shift component, the shift in regional economic growth in Ngada Regency to the economy at the NTT Province level is positive; and the Differential Shift component, the economy of Ngada Regency to the economy at the NTT Province level is negative, meaning that all capture fisheries potential in Ngada Regency has poor competitiveness with other regions/districts in NTT Province.

91 Mealworm and black soldier fly larvae as protein supplements for beef steers consuming forage

Abstract The global population is projected to increase, indicating there will be greater demand for animal protein to meet the associated food needs. This demand will place additional pressure on livestock systems to increase output while also minimizing natural resource inputs. Insect protein has emerged as a potential environmentally sustainable alternative to conventional protein feeds, such as soybean meal. Further, insect protein does not compete in the human food market as the products of conventional oil crops often do. Mealworm larvae (MWL) has been studied in poultry and swine as an alternative protein feed; however, there is not currently research evaluating MWL for cattle. Black soldier fly larvae (BSFL) has also received attention for its potential use in livestock feed due to its scalability and nutritional value, but research in cattle is limited. The objective of this study was to evaluate the effects of whole dried MWL and defatted BSFL as protein supplements for cattle consuming forage. These procedures were approved by IACUC at Texas State University (#7726). Five ruminally cannulated steers were utilized in a 5×5 Latin square experiment to determine how MWL and BSFL supplementation affect forage utilization. Steers consuming low-quality forage (4.2% crude protein) were provided one of five treatments each period: 1) control with no supplement (CON), 2) soybean meal (CONV), 3) BSFL, 4) MWL, and a 5) 50% BSFL and 50% MWL by-weight (MIX). Supplements were provided at 100 mg N/kg BW. Periods included 8-d for treatment adaptation, 5-d for intake and digestion measurements, and 1-d for ruminal fermentation measures. Dry matter (DM), organic matter (OM), CP, neutral detergent fiber (NDF), and acid detergent fiber (ADF) were determined for diet, ort, and feces. Protein supplementation stimulated forage OM intake (P ≤ 0.01) relative to CON. There was a significant difference in FOMI (P ≤ 0.01) between BSFL and CONV. Steers receiving CONV treatment consumed 4.71 kg FOMI/d, which was significantly greater (P ≤ 0.01) than those receiving BSFL (4.30 kg/d). There were not differences in FOMI between other treatment groups. Total digestible OM intake (TDOMI) was stimulated by protein supplementation (P ≤ 0.01) from 1.94 kg/d for CON to an average of 3.24 kg/d across protein supplements. Organic matter digestibility (OMD) and neutral detergent fiber digestibility (NDFD) were not affected by treatment (P ≥ 0.37), for an average OMD of 66.5% and NDFD of 62.7%. There was also not a treatment effect (P = 0.96) on total volatile fatty acid (VFA) concentrations, although there were some shifts in molar proportions of individual VFAs across treatments. These data indicate that MWL may be more efficacious than BSFL in stimulating forage utilization in beef cattle, but both are viable protein supplements.

Impact of the Madden–Julian oscillation and equatorial waves on tracked mesoscale convective systems over southeast Asia

AbstractSoutheast Asia is a region dominated by high‐impact weather, but numerical weather prediction here is a challenge owing to the complex orography and interactions between small‐ and large‐scale phenomena. Localised mesoscale convective systems (MCSs) can produce intense precipitation. Here, we track MCSs over a 5‐year period in Himawari satellite data, characterise the distribution of MCSs in the region, and investigate how they are modulated by the Madden–Julian oscillation (MJO) and equatorial waves. Between 10°S and 10°N in southeast Asia, MCSs account for 45–70% of the precipitation during boreal extended winter (November–April). Over most of the region, the fractional MCS contribution to rainfall is higher than average on days with extreme rainfall (&gt;55%). Long‐lived (&gt;12 hr) MCSs contribute disproportionately, providing 85% of the rainfall despite comprising only 34% of all MCSs. Variability in MCS rainfall accounts for &gt;50% of the total rainfall variability during an MJO cycle, mostly due to larger numbers of MCSs in convectively active MJO phases. Variations in MCS size and mean rain rate due to shifts in the stratiform proportion provide compensating effects. In the west of the region, a shift to faster moving MCSs in active MJO phases and slower moving MCSs in inactive phases resulted in fast‐moving MCSs having the greatest impact on the MJO‐associated variability. Variability is larger in the west than in the east. Equatorial Kelvin waves modulate MCS rainfall, with MCSs accounting for 20–50% of local rainfall anomalies. This variability is again enhanced in the west. By contrast, rainfall anomalies due to westward‐propagating mixed Rossby–gravity waves and Rossby‐1 waves are dominated by tropical‐cyclone‐related rainfall. Skill at local scales may be extracted from forecasts of subseasonal drivers such as the MJO and Kelvin waves, by understanding how these modulate the number and characteristics of MCSs.

P078 Inflammatory transcriptomic signatures and cell type compositions in colonic mucosa of ulcerative colitis

Abstract Background Previous studies have explored transcriptomic profiles associated with active inflammation in patients with IBD patients, but consistent characteristics of gene expression and enriched pathways, particularly in Asian patients with UC, remain unconfirmed. Here, we aimed to assess distinctive transcriptomic changes associated with persistent active mucosal inflammation in Asian patients with UC despite of medical treatment. Methods We obtained colonic mucosa biopsies of inflamed and noninflamed tissue from 15 patients with UC and 15 healthy controls and performed RNA sequencing analysis. Utilizing publicly available single cell RNA sequencing (scRNAseq) data, we also identified cell types expressing differentially expressed genes from RNAseq data and performed data deconvolution using CIBERSORTx. Results Transcriptomics profiling revealed that the inflammatory transcriptomic signature was highly enriched in the colonic mucosa of UC-active compared to UC-inactive and controls. By incorporating scRNAseq data, the genes upregulated in UC-active were highly expressed in M cells, inflammatory monocytes, and inflammatory fibroblasts, while downregulated genes were prominent in BEST4+ enterocytes and WNT5B+ fibroblasts. Notably, a sub-cluster of enterocytes associated with SAA1, SLC6A14, and DUOXA2 genes exhibited high expression in UC-active. Deconvolution analysis using CIBERSORTx identified significant enrichment of natural killer cells, inflammatory monocytes, Tuft cells, inflammatory fibroblast, WNT2B+Fos-lo1, and pericytes in UC-active. Conclusion Our RNAseq analysis not only identified significant gene expression changes but also revealed shifts in cell type proportions associated with persistent inflammation. These findings offer valuable insights for developing novel treatment strategies for UC.

Pemetaan Potensi Sektor Ekonomi di Kota Kediri Jawa Timur

The purpose of this study is to analyze the potential of each economic sector in Kediri City by identifying which sectors are basic and which are growing relatively fast, because economic growth and community welfare are one of the factors. The data used consists of secondary data obtained from the Central Bureau of Statistics (BPS) of Kediri City and East Java from 2019 to 2021. In addition, the quantitative descriptive approach used in this research is also used. By using methods such as Location Quotient (LQ) analysis, Shift Share analysis, and Klassen Typology analysis. The results showed that based on LQ analysis Kediri City has 1 base sector which is the manufacturing sector, based on Proportional Shift Share analysis there are 7 sectors that grow relatively fast, based on Regional Potential Shift Share analysis there are 9 sectors that tend to encourage the growth of East Java GRDP, and based on Differential Shift Share analysis there are 5 sectors that have local advantages. Kediri City is also included in the category of "Advanced but Depressed Region" in Klassen's Typology.&#x0D; &#x0D; Keywords: Economic Sector, GRDP , Klassen Typology, Location Quotient, Shift Share

Alterations in Immune Cell Composition during First-Line Therapy with Mosunetuzumab for Follicular or Marginal Zone Lymphoma

Background: Bispecific CD20xCD3 antibodies (BiAbs) that engage T-cells to eliminate CD20+ B-cells have emerged as a potent immunotherapy for the treatment of follicular (FL) and marginal zone (MZL) lymphomas. BiAbs have primarily been studied in patients with extensive prior immunosuppressive and lymphodepleting therapies, so their effects on the immune system without such exposures are not well understood. Unlike cellular therapies, BiAbs are administered continuously over time, spanning from 6 months to an indefinite period, and recent studies have raised concerns about T-cell exhaustion due to continuous BiAb exposure in B-lymphoblastic leukemia (Philipp et al, Blood 2022). Mosunetuzumab is a BiAb approved for treatment of relapsed/refractory FL. The ongoing phase 2 BrUOG-401 trial (NCT04792502) is investigating mosunetuzumab as first-line therapy for FL or MZL. Here, we present preliminary results focusing on treatment-induced changes in circulating immune cells. Methods: Patients with previously untreated, high-burden or symptomatic FL or MZL received subcutaneous mosunetuzumab for 8 planned cycles (C) with step-up dosing in C1 (day 1: 5mg, day 8 &amp; 15: 45 mg; then 45mg on day 1 of C4-C8). Patients without a complete response (CR) at interim assessment after C4 also received lenalidomide augmentation (10mg daily) during C5-8. Immune cell subsets were examined using multicolor flow cytometry (BD LSRII Analyzer). Peripheral blood samples were collected longitudinally before C1, on day 1 of C2 and C5, and 4-6 weeks after the end of therapy (EOT). Median cell abundance and marker expression were compared using generalized linear mixed models with patient and sample-level random effects. Analysis was performed in R (v.4.3.1) using the flowCore, flowStats and diffcyt packages; uncorrected P&amp;lt;0.05 was considered statistically significant. Results: As of July 2023, 13 patients (median age 62, 77% women, 77% FL, 23% MZL) were accrued in the trial. At data cutoff, 7 have completed therapy, 11 were evaluable for response, and 8 attained CR ( Fig. A). So far, only 1 patient started lenalidomide; samples collected while on lenalidomide were excluded from analysis. No instances of cytokine release syndrome (CRS) or neurotoxicity were observed. CR's occurred early (by C5). Mosunetuzumab resulted in a rapid, deep, and sustained depletion of circulating CD19+ B-cells. A significant decrease in circulating CD8+ T-cells was noted at cycle 2 (from median 20% to 12%, P&amp;lt;0.001; Fig. B), followed by recovery (19% at C5). Among the CD8+ subsets, the naïve CD8+ T-cells (CD45RA+CCR7+CD27+) decreased relatively at C5 &amp; EOT, while effector memory T-cells (CD45RA-CD45RO+CD27-CD62L-) increased. Notably, we observed a significant early, temporary, increase in the expression of LAG3 at C2 on CD8+ T-cells ( P=0.033), and a more pronounced increase in PD1 expression ( P=0.001), which persisted through the EOT ( Fig. B). No significant changes were observed in total abundance of CD4+ T-cells. However, CD4+CD25+CD127- Tregs notably increased at C2 ( P=0.008). This increase specifically driven by CD45RA+ “naïve” Tregs ( P&amp;lt;0.001 at C2), which remained elevated relative to CD45RO+ Tregs at C5 and EOT. All Tregs showed a significant increase in LAG3 expression at C2 ( P&amp;lt;0.001), which then subsided. In contrast to CD8+ T-cells, there was no significant increase in PD1 expression on CD4+ T-cells ( P=0.20 at C2). Throughout the therapy, there was a progressive increase in NK cells ( P=0.001 at EOT), with no significant shift in the relative proportions of CD16high or CD161high NK cells. Conclusions: In this initial investigation of immune cell changes in patients who received mosunetuzumab without prior chemotherapy exposure, we observed B-cell depletion and a temporary decrease in CD8+ cytotoxic T-cells (implying their migration out of the bloodstream), aligning with mosunetuzumab's mechanism of action. Additional data from this trial will aid in understanding whether the persistent increase in PD1+CD8+ T-cells and expansion of Tregs are linked to a functionally exhausted phenotype and whether lenalidomide could potentially reverse it. Although our observation is limited by sample size, it can still provide insights into optimizing the administration schedules of BiAb therapy in future trials (e.g., intermittent vs. continuous) or determining the most suitable timing for checkpoint inhibitor combinations.