Long-term Response Research Articles

Long-term responses of phytoplankton biomass to the ocean surface variables in the central parts of the Arabian Sea and the Bay of Bengal

The northern Indian Ocean has been warming steadily for over a half-century, especially the north-western Indian Ocean. It is widely reported that the increasing sea surface temperature in the global oceans decreases phytoplankton biomass and productivity. The impacts of long-term variations in the sea surface properties on the phytoplankton biomass (chlorophyll a) are least studied in the northern Indian Ocean. In this study, we have retrieved satellite, model, and ARGO float data sets to investigate the long-term variations in the distributions and trends of major oceanic variables for a better understanding of the respective changes that occurred in chlorophyll a concentration in the central regions of the Arabian Sea (AS) and the Bay of Bengal (BB). We have selected variables such as sea surface temperature (SST), sea surface salinity (SSS), photosynthetically available radiation (PAR), euphotic depth (ZEU), mixed layer depth (MLD), wind speed, mean sea level anomaly (MSLA), surface currents, etc., to relate with chlorophyll a. We found significant increasing trends in SST and positive-MSLA in both basins, and the chlorophyll a was decreased in the AS but contrastingly increased in the BB. Further data analysis revealed the possible reasons, such as seasonal changes in mean sea level anomaly and meridional currents, for the increasing trend of chlorophyll a in the central Bay of Bengal. The northward flow of the meridional currents during the southwest monsoon (SWM), transports the nutrient-rich water from the coastal upwelling zone of the southwest coast of India to the southern and central BB, and enhances chlorophyll a. Contrastingly, the southward flow of low-saline and nutrient-depleted Bay of Bengal water reduces the chlorophyll a. In addition, the large area of cold-core eddies found during the NEM enhanced the chlorophyll a in the central BB. Though contrasting trends between both basins in chlorophyll a distribution were found, the mean concentration of chlorophyll a in the northern Indian Ocean decreases. The present study signifies the importance of monsoon currents and eddies in regulating the chlorophyll a biomass and primary productivity in the AS and BB.

1326P Clinical and genomic characteristics of advanced non-small cell lung cancer (aNSCLC) patients (pts) with long-term response to first-line (1L) immunotherapy: A real-world study

1326P Clinical and genomic characteristics of advanced non-small cell lung cancer (aNSCLC) patients (pts) with long-term response to first-line (1L) immunotherapy: A real-world study

134 Serial 4DPET/4DCT Imaging to Predict Long-Term Response After Chemo-Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer

134 Serial 4DPET/4DCT Imaging to Predict Long-Term Response After Chemo-Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer

101P Circulating tumor DNA minimal residual disease predicts the risk of progression after long-term response to first-line immunotherapy in advanced NSCLC

101P Circulating tumor DNA minimal residual disease predicts the risk of progression after long-term response to first-line immunotherapy in advanced NSCLC

Real-world evidence of allergen immunotherapy.

The full understanding of the long-term effectiveness and safety of allergen immunotherapy (AIT) for allergic respiratory diseases cannot be achieved through randomized controlled trials (RCTs) alone. However, real-world studies designed as registries can complement RCTs. The significance of registries is highlighted by their potential to reassess contraindications and collect data on adult and pediatric patients with multiple comorbidities who are often excluded from RCTs. AIT is the sole disease-modifying therapeutic approach capable of inducing tolerance and offering a long-term response to allergens. AIT has been shown to play a role in arresting the 'allergic march' in young people, which reduces the risk of developing asthmatic clinical manifestations. Although RCTs are considered the gold standard for evaluating the efficacy and safety of AIT, their duration is usually too short (seldom lasting more than 1 year) to assess the long-term effects of AIT. Several long-term studies show that AIT's effect depends strongly on its use duration.

Severe Acute Respiratory Syndrome and COVID-19 Under the Urban Hierarchy of Municipalities in the State of Rondônia (Western Amazon)

Analyzing the SARS data can provide insights into the severe form of COVID-19, contributing to short, medium, and long-term pandemic response planning. The virus entered Brazilian through air travel, spreading via airport connections. The spatial diffusion of COVID-19 transmission is linked to the territorial division of labor (referring to characteristic daily activities), as reflected in the urban hierarchical network, which serves as a framework for analyzing COVID-19 transmission. This analysis covers mobility aspects such as density, connectivity and the movement of people at different scales. The objective is to evaluate the transmission of SARS and COVID-19 in the state of Rondônia, Western Amazon, between 2020 and 2021, using geoprocessing techniques for spatiotemporal analysis. Maps depicting the urban hierarchy (understood as cities organized by size, from smallest to largest) of the municipalities of Rondônia, along with SARS incidence rates and their standard deviation, were created using QGIS program, version 2.18.20. Spatiotemporal analysis was conducted using Kulldorff statistics to identify clusters of SARS cases in each municipality. A higher concentration of SARS rates ​​was observed in municipalities in the northwestern part of the state. Six spatiotemporal clusters were identified, but no clear pattern of spatial distribution was observed. The spatial diffusion of COVID-19 transmission is linked to the territorial division of labor (i.e., the spatial classification based on the predominant economic activity in each area), as evidenced by the urban hierarchical network, which serves as a reference for analyzing COVID-19 transmission.

Long-term hypoxia-induced physiological response in turbot Scophthalmus maximus L.

Hypoxia affects fish's survival, growth, and physiological metabolism processes. In this study, turbot plasma glucose and cortisol contents, hepatic glycolysis (hexokinase [HK], phosphofructokinase [PFK], pyruvate kinase [PK]) and lipolysis (fatty acid synthetase [FAS], lipoprotein lipase [LPL]) enzyme activities, anti-oxidant enzyme (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px]) activities, malondialdehyde (MDA), lactate and glycogen contents, gill histological parameters (lamellar length [SLL], width [SLW], interlamellar distance [ID]), respiratory frequency (RF), the proportion of the secondary lamellae available for gas exchange (PAGE), and hifs (hif-1α, hif-2α, hif-3α) expression were determined during long-term hypoxia and reoxygenation. Results showed that long-term hypoxia (3.34 ± 0.17mg L-1) significantly elevated plasma cortisol and glucose contents; increased hepatic HK, PK, PFK, FAS, and LPL activity; decreased hepatic glycogen, lactate contents, and lipid drop numbers; and caused changes of hepatocyte (vacuolation, pyknotic, and lytic nucleus) after treatment for 4weeks. Hepatic SOD, CAT, GSH-Px activity, and MDA contents; lamellar perimeter, SLL, ID, RF, and PAGE; and hepatic hif-1α, hif-2α, and hif-3α manifested similar results. Meanwhile, hif-1α is significantly higher than hif-2α, and hif-3α. Interestingly, females and males demonstrated no sex dimorphism significantly different from the above parameters (except hepatic FAS, LPL activity, and lipid drop number) under hypoxia. The above parameters recovered to normal levels after reoxygenation treatment for 4weeks. Thus, long-term hypoxia promotes turbot hepatic glycogenolysis and lipolysis, induces oxidative damage and stimulates hepatic antioxidant capacity, and alters gill morphology to satisfy insufficient energy demand and alleviate potential damage, while hif-1α plays critical roles in the above physiological process.

Long-term cytokine profile in multisystem inflammatory disease among children

BackgroundMultisystem inflammatory disease in children (MIS-C) is a post-infectious condition following coronavirus disease-19 infection. Long-term follow-up data suggests that initial clinical severity does not necessarily correlate with long-term outcomes. The long-term immunological response in children with MIS-C remains poorly understood. We analyzed cytokine profiles at diagnosis and during follow-up, in pediatric patients with MIS-C, exploring correlations among cytokine expressions and standard biochemical and hormonal test results. MethodsTwenty-five MIS-C patients (mean 9.4 ± 3.9) with complete test results at diagnosis and at 6- and 12-months follow-up were included in the study. Selected cytokines, such as IL-9, eotaxin, IP-10, MIP-1β, RANTES, MCP-1(MCAF), TNF-α, PDGF-B, IL-4, and MIP-1α, were included in the analysis. ResultsIP-10, MCP-1 (MCAF), and MIP-1α levels normalized or nearly normalized at 6–12 months, the remaining cytokines, including IL-9, eotaxin, MIP-1β, RANTES, TNF-α, PDGF-B, IL-4, remained higher in MIS-C than in controls at our last follow-up time. At 6 months post-diagnosis, a mild negative correlation between triglycerides and HOMA-IR with MCP-1 (MCAF), IL-4, and Eotaxin was noted. At the 12-month follow-up we found a mild positive correlation of cortisol and ACTH levels with PDGF-B, MIP-1α, and TNF-α. Conversely, a negative correlation between these cytokines with fasting glucose and HOMA-IR was observed. ConclusionsOur study findings highlight a notable cytokine-mediated inflammatory response in pediatric patients with MIS-C, characterized by sustained elevated levels over a 12-month monitoring period compared to the control group. We have identified various interrelationships among different cytokines, as well as correlations between heightened cytokine levels and metabolic and hormonal patterns. The pronounced inflammatory response underscores its involvement in acute organ damage, while its persistence suggests potential implications for long-term metabolic disorders.

MPN-652 Long-Term Response to Selinexor in Patients With Myelofibrosis and Refractory or Intolerant to JAK Inhibitors: Follow-Up Results of a Single-Center, Phase II, Investigator-Initiated Trial (IIT)

MPN-652 Long-Term Response to Selinexor in Patients With Myelofibrosis and Refractory or Intolerant to JAK Inhibitors: Follow-Up Results of a Single-Center, Phase II, Investigator-Initiated Trial (IIT)

Long-Term Response to Selinexor in Patients With Myelofibrosis and Refractory or Intolerant to JAK Inhibitors: Follow-Up Results of a Single-Center, Phase II, Investigator-Initiated Trial (IIT)

Long-Term Response to Selinexor in Patients With Myelofibrosis and Refractory or Intolerant to JAK Inhibitors: Follow-Up Results of a Single-Center, Phase II, Investigator-Initiated Trial (IIT)

Thermo-hydro-mechanical viscoplastic constitutive model for polyester strap reinforcement long-term response

Polymeric materials have been shown to be rate-dependent materials, that is, their response will vary depending on the conditions to which they are subjected. The present work details the formulation, validation and implementation of a viscoplastic constitutive model with stress, strain, temperature, and relative humidity dependencies aimed to simulate the long-term response of polymeric materials, particularly that of polyester. The model is capable of predicting primary and secondary creep, often observed in geosynthetic materials. Both creep mechanisms can be modelled independently if needed. For calibration, a wide data-set of polyester strap reinforcement creep measurements was used. The validation process was done using parameters for load-, product-, and material-specific scenarios. Load- and product-specific scenarios showed suitable agreement between simulated and measured data. The coupled capabilities of the model are shown via variable temperature and relative humidity boundary conditions. Due to lack of data, temperature and relative humidity dependencies represent idealized scenarios. Simulations of stress-relaxation response for constant rate of strain scenarios are also provided. The proposed formulation is aimed at modelling the mechanical response of reinforced soil structures while accounting for the effect of in-air or in-soil conditions to which reinforcement materials can be exposed to throughout the structure’s life-cycle.

Dynamic management of ground thermal response uncertainty through temporal analysis of parameter sensitivity

Accurately estimating the dimensionless ground thermal response factor (g-function) is critical for the design and operation of geothermal energy systems. This process, however, is fraught with uncertainties stemming from the difficulty in controlling on-site geometric parameters and estimating thermal properties through field experiments. The relative contributions of these parameters to response uncertainty change temporally as the response progresses. Thus, understanding this temporal sensitivity variation is crucial for effective response uncertainty management. To address this, we conducted transient global sensitivity analyses. Regardless of borefield setups, ground thermal properties were key factors in thermal response uncertainty. However, their influence decreased from the late-mid term as borehole radius and borehole distance became more significant in single-borehole and multi-borehole setups, respectively. This time-varying relative sensitivity suggests that prioritizing parameters to reduce response uncertainty depends on the temporal characteristics of the ground load. To demonstrate this, we systematically halved the uncertainty for each parameter and examined the resultant change in the fluid temperature uncertainty for a dynamic ground load scenario. Notably, prioritizing parameters with high early-response sensitivity significantly reduced fluid temperature uncertainty. These findings highlight the need for dynamic uncertainty management strategies in geothermal system design and operation. For dynamic load profiles utilizing the ground as a heat source or sink, prioritizing parameters with high sensitivity in the early- to mid-term is crucial. Conversely, for long-term storage applications, focusing on parameters with high sensitivity in the mid- to long-term response becomes essential.

Patient selection, ventricular tachycardia substrate delineation and data transfer for stereotactic arrhythmia radioablation. A Clinical Consensus Statement of the European Heart Rhythm Association (EHRA) of the ESC and the Heart Rhythm Society (HRS).

Stereotactic arrythmia radioablation (STAR) is a novel, non-invasive and promising treatment option for ventricular arrythmias (VA). It has been applied in highly selected patients mainly as bail-out procedure, when (multiple) catheter-ablations, together with anti-arrhythmic drugs, were unable to control the VAs. Despite the increasing clinical use there is still limited knowledge of the acute and long-term response of normal and diseased myocardium to STAR. Acute toxicity appeared to be reasonably low but potential late adverse effects may be underreported. Among published studies, the provided methodological information is often limited, and patient selection, target volume definition, methods for determination and transfer of target volume, and techniques for treatment planning and execution differ across studies, hampering pooling of data and comparison across studies. In addition, STAR requires close and new collaboration between clinical electrophysiologists and radiation oncologists, which is facilitated by shared knowledge in each collaborator's area of expertise and a common language. This clinical consensus statement provides uniform definition of cardiac target volumes. It aims to provide advice in patient selection for STAR including etiology specific aspects, and advice in optimal cardiac target volume identification based on available evidence. Safety concerns and the advice for acute and long-term monitoring including the importance of standardized reporting and follow-up are covered by this document. Areas of uncertainty are listed, which require high-quality, reliable pre-clinical and clinical evidence before expansion of STAR beyond clinical scenarios in which proven therapies are ineffective or unavailable.

Overcoming Resistance to Checkpoint Inhibitors with Combination Strategies in the Treatment of Non-Small Cell Lung Cancer.

Lung cancer continues to contribute to the highest percentage of cancer-related deaths worldwide. Advancements in the treatment of non-small cell lung cancer like immune checkpoint inhibitors have dramatically improved survival and long-term disease response, even in curative and perioperative settings. Unfortunately, resistance develops either as an initial response to treatment or more commonly as a progression after the initial response. Several modalities have been utilized to combat this. This review will focus on the various combination treatments with immune checkpoint inhibitors including the addition of chemotherapy, various immunotherapies, radiation, antibody-drug conjugates, bispecific antibodies, neoantigen vaccines, and tumor-infiltrating lymphocytes. We discuss the status of these agents when used in combination with immune checkpoint inhibitors with an emphasis on lung cancer. The early toxicity signals, tolerability, and feasibility of implementation are also reviewed. We conclude with a discussion of the next steps in treatment.

Region-Specific Gene Expression Changes Associated with Oleoylethanolamide-Induced Attenuation of Alcohol Self-Administration.

Oleoylethanolamide (OEA) is a lipid with anti-inflammatory activity that modulates multiple reward-related behaviors. Previous studies have shown that OEA treatment reduces alcohol self-administration (SA) while inhibiting alcohol-induced inflammatory signaling. Nevertheless, the specific mechanisms that OEA targets to achieve these effects have not been widely explored. Here, we tested the effects of OEA treatment during alcohol SA, extinction or previous to cue-induced reinstatement of alcohol seeking. In addition, we measured gene expression changes in the striatum and hippocampus of relevant receptors for alcohol consumption (Drd1, Drd2, Cnr1, Oprm) as well as immune-related proteins (Il-6, Il-1β, Tlr4) and the brain-derived neurotrophic factor (Bdnf). Our results confirmed that when administered contingently, systemic OEA administration reduced alcohol SA and attenuated cue-induced reinstatement. Interestingly, we also observed that OEA treatment reduced the number of sessions needed for the extinction of alcohol seeking. Biochemical analyses showed that OEA induced gene expression changes in dopamine and cannabinoid receptors in the striatum and hippocampus. In addition, OEA treatment modulated the long-term immune response and increased Bdnf expression. These results suggest that boosting OEA levels may be an effective strategy for reducing alcohol SA and preventing relapse.

Modulation of the Hyperglycemia Condition in Diabetic Lab Rats with Extracts of the Creole Jamaica Flower (Hibiscus sabdariffa L.) from the Morelia Region (Mexico).

Extracts from Jamaica flowers (Hibiscus sabdariffa) from Morelia (Mexico) were evaluated as antidiabetic ingredients in a diabetic rat lab model for 80 days at doses of 200, 400, and 600 mg extract/kg rat weight. The hydroalcoholic extract (water:ethanol 80:20 (v/v) at 50 °C) showed a TPC value of 403.28 ± 7.71 mg GAE/g extract, and an antioxidant activity of 0.219 ± 0.00003 mmol Trolox/g (ABTS) and 0.134 ± 0.00001 mmol Trolox/g (DPPH). The extract allowed reducing the diabetic glucose plasma levels under fasting conditions in a dose-dependent manner by 35.2%, 41.63%, and 50.1%. Additionally, the highest dose of the extract (600 mg/kg) slightly reduced the short-term postprandial glucose response while improving the long-term response, reducing hyperglycemia by 45.1%. The same dose also improved lipid metabolism by reducing total cholesterol, triglycerides, VLDL, and LDL, while the HDL level increased. The improvement in glucose and lipid management in the treated groups also led to reduced levels of glycosylated hemoglobin, as well as lower insulin resistance (TyG index), compared to the diabetic control group. The results of this study suggest that extracts from Hibiscus sabdariffa (Morelia) can be used as potential functional ingredients or nutraceuticals for managing the diabetic condition.

Long-term exposure and response to azacitidine for post-hematopoietic stem cell transplantation relapse of early T-cell precursor acute lymphoblastic leukemia: a case report and review of the literature

Adult T-cell acute lymphoblastic leukemia has a poor outcome after relapse. Because the subtype of early T-cell precursor displays characteristics close of those of acute myeloid leukemia, such as epigenetic dysregulation, hypomethylating agents might prove of interest. We describe the case of a patient relapsing 3 months only after allogeneic stem cell transplantation who achieved complete remission on azacitidine, and is still on therapy 9 years later. We discuss the biological background of this very long-term response, underlining the immunological effects of hypomethylating agents, and the perspectives opened by combination of hypomethylating agents with other drugs such as venetoclax.

Baseline Gut Microbiota Was Associated with Long-Term Immune Response at One Year Following Three Doses of BNT162b2.

This study explored neutralizing IgG antibody levels against COVID-19 decline over time post-vaccination. We conducted this prospective cohort study to investigate the function of gut microbiota in the host immune response following three doses of BNT162b2. Subjects who received three doses of BNT162b2 were recruited from three centers in Hong Kong. Blood samples were obtained before the first dose and at the one-year timepoint for IgG ELISA to determine the level of neutralizing antibody (NAb). The primary outcome was a high immune response (NAb > 600 AU/mL). We performed shotgun DNA metagenomic sequencing on baseline fecal samples to identify bacterial species and metabolic pathways associated with high immune response using linear discriminant analysis effect size analysis. A total of 125 subjects were recruited (median age: 52 years [IQR: 46.2-59.0]; male: 43 [34.4%]), and 20 were regarded as low responders at the one-year timepoint. Streptococcus parasanguinis (log10LDA score = 2.38, p = 0.003; relative abundance of 2.97 × 10-5 vs. 0.03%, p = 0.001), Bacteroides stercoris (log10LDA score = 4.29, p = 0.024; relative abundance of 0.14% vs. 2.40%, p = 0.014) and Haemophilus parainfluenzae (log10LDA score = 2.15, p = 0.022; relative abundance of 0.01% vs. 0, p = 0.010) were enriched in low responders. Bifidobacterium pseudocatenulatum (log10LDA score = 2.99, p = 0.048; relative abundance of 0.09% vs. 0.36%, p = 0.049) and Clostridium leptum (log10LDA score = 2.38, p = 0.014; relative abundance of 1.2 × 10-5% vs. 0, p = 0.044) were enriched in high responders. S. parasanguinis was negatively correlated with the superpathway of pyrimidine ribonucleotides de novo biosynthesis (log10LDA score = 2.63), which contributes to inflammation and antibody production. H. parainfluenzae was positively correlated with pathways related to anti-inflammatory processes, including the superpathway of histidine, purine, and pyrimidine biosynthesis (log10LDA score = 2.14). Among three-dose BNT162b2 recipients, S. parasanguinis, B. stercoris and H. parainfluenzae were associated with poorer immunogenicity at one year, while B. pseudocatenulatum and C. leptum was associated with a better response.

Simulating within-field spatial and temporal corn yield response to nitrogen with APSIM model

ContextProcess-based crop growth models can explain soil and crop dynamics that influence the optimal N rate for crop production. Currently, there is a lack of understanding regarding the accuracy of process-based models for site-specific zones within fields, as well as the key factors that need to be considered when calibrating these models for zone-specific economic optimum N rate (EONR).ObjectiveWe calibrated the Agricultural Production Systems sIMulator (APSIM) model in contrasting zones within fields, quantified the model performance, and used the calibrated model to develop long-term corn yield response to N to assess the temporal variability between zones and sites to assist decision making.MethodsWe conducted four N rate experiments (2 fields × 2 zones within a field) over two years in southeast Nebraska. Experimental data were used to calibrate and test the APSIM model. APSIM simulated corn yield response to N for each zone and site was obtained by running numerous iterations of the calibrated model at different N rates. Observed and simulated corn yield response to N rate were analyzed with statistical models to estimate the EONR.Results and conclusionsThe APSIM model predicted corn yield over 11 historical years with a relative root mean square error (RRMSE) of 12% and yield at EONR in the N studies with RRMSE of 8.8%. The simulated EONR was lower than the observed EONR across sites, years, and zones with greater error than yield. The simulated yield increase with N fertilization was under-estimated in fine textured soils and over-estimated in medium textured soils. Long-term corn yield response to N showed that temporal variation in simulated EONR was greater than spatial variation. Long-term EONR and yield at EONR increased with increasing rainfall, while yield at zero N was greatest in normal years. Temporal variation was driven primarily by year-to-year variation in N loss (CV of 67% ± 9.5). Soil texture, hydrological properties, water table, and tile drainage were key variables for accurate site-specific model calibration. Improvements in simulating site-specific EONR may be realized by including in-situ or remotely sensed data for better estimation of N dynamics. We concluded that APSIM can provide valuable insights into systems dynamics in this region, but it can’t provide precise N-rate estimates. Our study contributes to understanding of the within-field variability using simulation modeling.

Cross-cultural differences and acculturation in affective response and sensory perception: a case study across Chinese immigrants and local consumers in New Zealand

Understanding cross-cultural variation in perception is essential for identifying culture-specific factors impacting product acceptability. While immigrants may initially maintain their preferences, acculturation levels vary. To understand to what extent immigrants can be used as a proxy to model overseas markets, this study investigated short (CHS) and long-term (CHL) Chinese immigrant responses to plain yoghurts compared to New Zealand (NZ) Europeans (E). Three groups (CHS, CHL and NZE, n = 222) evaluated liking of, emotional response to, and sensory perception of 10 plain yoghurts. Groups liked yoghurts similarly. Notably, NZE rated emotions lower than both immigrant groups, with a few exceptions. Both Chinese groups rated most emotions similarly, but CHL rated some closer to NZE. Positive emotions correlated with higher liking scores. However, cross-cultural differences existed for ‘guilty’ which was associated with yoghurts liked by NZE; and for ‘wild’ and ‘mild’ associated with yoghurts disliked by both immigrant groups. Citation proportions for some sensory attributes differed among all groups, dependent on the sample. But level of acculturation between immigrant groups was limited. Sweetness, vanilla, stone fruit and cream flavours, smoothness, and creaminess drove liking across all groups, whereas only the Chinese valued umami, undoubtedly due to positive associations with it. Some effects of acculturation for long-term immigrants were evident, but responses were often closer to their short-term counterparts. Therefore, immigrants in general provide a useful proxy for measuring consumer responses in early stages of product development for this overseas market, but with consideration of their residence time in the host culture.