Individual Responses Research Articles

LAPTM4B-mediated hepatocellular carcinoma stem cell proliferation and MDSC migration: implications for HCC progression and sensitivity to PD-L1 monoclonal antibody therapy

In hepatocellular carcinoma (HCC), immunotherapy is vital for advanced-stage patients. However, diverse individual responses and tumor heterogeneity have resulted in heterogenous treatment outcomes. Our mechanistic investigations identified LAPTM4B as a crucial gene regulated by ETV1 (a transcription factor), especially in liver cancer stem cells (LCSCs). The influence of LAPTM4B on LCSCs is mediated via the Wnt1/c-Myc/β-catenin pathway. CXCL8 secretion by LAPTM4B drove myeloid-derived suppressor cell (MDSC) migration, inducing unfavorable patient prognosis. LAPTM4B affected PD-L1 receptor expression in tumor microenvironment and enhanced tumor suppression induced by PD-L1 monoclonal antibodies in HCC patients. LAPTM4B up-regulation is correlated with adverse outcomes in HCC patients, sensitizing them to PD-L1 monoclonal antibody therapy.

Extended incubation recesses in sanderlings are impacted by temperature and body condition.

Complex incubation strategies have evolved to solve the trade-off between parent survival and care for their eggs with often brief departures (recesses) that maximize egg survival, and infrequent extended recesses maximizing adult condition. Here we examined incubation behaviour of sanderlings (Calidris alba), a species that exhibits both biparental and uniparental incubation behaviour. During 11 breeding seasons in Greenland, we have quantified incubation variability with thermologgers placed in nests. We estimated the impact of environmental conditions and individual characteristics on the occurrence and the duration of recesses. We found that extended recesses are a unique feature of uniparentals, and their frequency and duration increased in colder temperatures. The relationship was mediated by body condition, with individuals in poor condition performing longer extended recesses in colder temperatures. This suggests that extended recesses may represent a shift towards self-maintenance at the expense of the egg care, allowing birds to continue incubating under unfavourable conditions. Our study illustrates how extended recesses may be a key breeding strategy to overcome high energetic costs associated with incubation. Quantifying such behavioural flexibility paves the way for tracking future behavioural responses of individuals in the face of changing environments.

The impact of using reinforcement learning to personalize communication on medication adherence: findings from the REINFORCE trial

Text messaging can promote healthy behaviors, like adherence to medication, yet its effectiveness remains modest, in part because message content is rarely personalized. Reinforcement learning has been used in consumer technology to personalize content but with limited application in healthcare. We tested a reinforcement learning program that identifies individual responsiveness (“adherence”) to text message content and personalizes messaging accordingly. We randomized 60 individuals with diabetes and glycated hemoglobin A1c [HbA1c] ≥ 7.5% to reinforcement learning intervention or control (no messages). Both arms received electronic pill bottles to measure adherence. The intervention improved absolute adjusted adherence by 13.6% (95%CI: 1.7%–27.1%) versus control and was more effective in patients with HbA1c 7.5- < 9.0% (36.6%, 95%CI: 25.1%–48.2%, interaction p < 0.001). We also explored whether individual patient characteristics were associated with differential response to tested behavioral factors and unique clusters of responsiveness. Reinforcement learning may be a promising approach to improve adherence and personalize communication at scale.

Examining surgeon stress in robotic and laparoscopic surgery.

Robotic surgery may decrease surgeon stress compared to laparoscopic. To evaluate intraoperative surgeon stress, we measured salivary alpha-amylase and cortisol. We hypothesized robotic elicited lower increases in surgeon salivary amylase and cortisol than laparoscopic. Surgical faculty (n = 7) performing laparoscopic and robotic operations participated. Demographics: age, years in practice, time using laparoscopic vs robotic, comfort level and enthusiasm for each. Operative data included operative time, WRVU (surgical "effort"), resident year. Saliva was collected using passive drool collection system at beginning, middle and end of each case; amylase and cortisol measured using ELISA. Standard values were created using 7-minute exercise (HIIT), collecting saliva pre- and post-workout. Linear regression and Student's t test used for statistical analysis; p values < 0.05 were significant. Ninety-four cases (56 robotic, 38 laparoscopic) were collected (April-October 2022). Standardized change in amylase was 8.4 ± 4.5 (p < 0.001). Among operations, raw maximum amylase change in laparoscopic and robotic was 23.4 ± 11.5 and 22.2 ± 13.4; raw maximum cortisol change was 44.21 ± 46.57 and 53.21 ± 50.36, respectively. Values normalized to individual surgeon HIIT response, WRVU, and operative time, showing 40% decrease in amylase in robotic: 0.095 ± 0.12, vs laparoscopic: 0.164 ± 0.16 (p < 0.02). Normalized change in cortisol was: laparoscopic 0.30 ± 0.44, robotic 0.22 ± 0.4 (p = NS). On linear regression (p < 0.001), surgeons comfortable with complex laparoscopic cases had lower change in normalized amylase (p < 0.01); comfort with complex robotic was not significant. Robotic may be less physiologically stressful, eliciting less increase in salivary amylase than laparoscopic. Comfort with complex laparoscopic decreased stress in robotic, suggesting laparoscopic experience is valuable prior to robotic.

Human emergency behaviour and psychological stress characteristic mining based on large-scale emergencies

AbstractHuman emergency behaviour and psychological stress response in emergencies are important scientific issues in basic emergency management research. The analysis of the dynamic characteristics of large-scale human behaviour based on electronic footprint data provides a new method for quantitative research on this problem. Previous studies usually assumed that human behaviors were randomly distributed in time, but few studies have studied the psychological stress response of human groups under the influence of emergencies and carried out prediction methods through social media data. Based on the data from five emergencies and daily events in the Qzone, this paper explores the statistical characteristics of human communication behaviors such as time, space and social interaction. The research results reveal the psychological evolution of human groups when they encounter public security emergencies by analysing the causes of individual psychological stress responses in the group. We find that the time interval between people’s posting behaviour and interactive comment behaviour in mobile QQ space before and after an emergency can be approximately described by a power-law distribution. The time interval distribution of Posting and reply is an obvious heavy-tailed distribution. These behavioural characteristics are consistent with people’s psychological stress characteristics. Individual psychological stress responses gradually evolve into social-psychological responses with changes in behavioural characteristics. The greater the social-psychological stress response is, the more panic the public will be, which will cause the outbreak of group irrational behaviour. The research results are theoretically helpful in understanding the impact of emergencies on human communication behaviour patterns and reveal the psychological stress process of mass panic in large-scale emergencies.

Electroencephalography oscillations can predict the cortical response following theta burst stimulation

BackgroundContinuous theta burst stimulation and intermittent theta burst stimulation are clinically popular models of repetitive transcranial magnetic stimulation. However, they are limited by high variability between individuals in cortical excitability changes following stimulation. Although electroencephalography oscillations have been reported to modulate the cortical response to transcranial magnetic stimulation, their association remains unclear. This study aims to explore whether machine learning models based on EEG oscillation features can predict the cortical response to transcranial magnetic stimulation. MethodTwenty-three young, healthy adults attended two randomly assigned sessions for continuous and intermittent theta burst stimulation. In each session, ten minutes of resting-state electroencephalography were recorded before delivering brain stimulation. Participants were classified as responders or non-responders based on changes in resting motor thresholds. Support vector machines and multi-layer perceptrons were used to establish predictive models of individual responses to transcranial magnetic stimulation. ResultAmong the evaluated algorithms, support vector machines achieved the best performance in discriminating responders from non-responders for intermittent theta burst stimulation (accuracy: 91.30%) and continuous theta burst stimulation (accuracy: 95.66%). The global clustering coefficient and global characteristic path length in the beta band had the greatest impact on model output. ConclusionThese findings suggest that EEG features can serve as markers of cortical response to transcranial magnetic stimulation. They offer insights into the association between neural oscillations and variability in individuals' responses to transcranial magnetic stimulation, aiding in the optimization of individualized protocols.

A Comparative Study of Doctors and Nurses Regarding the Knowledge, Attitude and Practice of Basic Life Support in Tertiary Care Hospitals of Peshawar

Background: Basic Life Support (BLS) is a critical skill set for healthcare providers, enabling them to offer immediate assistance in cardiac emergencies. In Peshawar, Pakistan, the knowledge, attitude, and practice of BLS among doctors and nurses in tertiary care hospitals have not been extensively studied, despite the region's significant healthcare demands. Understanding these aspects can inform targeted improvements in BLS training and preparedness. Objective: This study aimed to evaluate and compare the knowledge, attitudes, and practices regarding BLS among doctors and nurses working in tertiary care hospitals in Peshawar, identifying gaps and areas for enhancement. Methods: A comparative cross-sectional study was conducted from July to October 2023. The sample comprised 249 healthcare professionals (102 doctors and 147 nurses) selected through convenience sampling. Participants were assessed using a validated questionnaire adapted from previous research, covering demographics, knowledge, attitude, and practice related to BLS. Data analysis utilized SPSS version 27, with descriptive statistics summarizing demographics, and inferential statistics (independent samples T-test) examining associations between knowledge levels and demographic variables. Results: The majority of participants were aged 26 to 30 years (47.4%), with nurses representing 59% of the sample. Knowledge assessment showed that 86.3% correctly identified the BLS abbreviation, but only 10.8% knew the correct first response for an unresponsive individual on the road. About 33.3% of participants displayed poor knowledge, with 49.0% demonstrating average knowledge. In practice scenarios, 56.2% exhibited poor practice. No significant differences were found in knowledge and practice based on gender or experience. Conclusion: The study highlights significant gaps in BLS knowledge and practice among healthcare providers in Peshawar's tertiary care hospitals, despite generally positive attitudes towards BLS. The findings underscore the need for enhanced BLS training programs, emphasizing practical skills and regular updates to guidelines. Addressing these educational gaps is crucial for improving patient outcomes in cardiac emergencies.

End-to-end deep learning method for predicting hormonal treatment response in women with atypical endometrial hyperplasia or endometrial cancer.

Endometrial cancer (EC) is the most common gynecologic malignancy in the United States, and atypical endometrial hyperplasia (AEH) is considered a high-risk precursor to EC. Hormone therapies and hysterectomy are practical treatment options for AEH and early-stage EC. Some patients prefer hormone therapies for reasons such as fertility preservation or being poor surgical candidates. However, accurate prediction of an individual patient's response to hormonal treatment would allow for personalized and potentially improved recommendations for these conditions. This study aims to explore the feasibility of using deep learning models on whole slide images (WSI) of endometrial tissue samples to predict the patient's response to hormonal treatment. We curated a clinical WSI dataset of 112 patients from two clinical sites. An expert pathologist annotated these images by outlining AEH/EC regions. We developed an end-to-end machine learning model with mixed supervision. The model is based on image patches extracted from pathologist-annotated AEH/EC regions. Either an unsupervised deep learning architecture (Autoencoder or ResNet50), or non-deep learning (radiomics feature extraction) is used to embed the images into a low-dimensional space, followed by fully connected layers for binary prediction, which was trained with binary responder/non-responder labels established by pathologists. We used stratified sampling to partition the dataset into a development set and a test set for internal validation of the performance of our models. The autoencoder model yielded an AUROC of 0.80 with 95% CI [0.63, 0.95] on the independent test set for the task of predicting a patient with AEH/EC as a responder vs non-responder to hormonal treatment. These findings demonstrate the potential of using mixed supervised machine learning models on WSIs for predicting the response to hormonal treatment in AEH/EC patients.

SARS-CoV-2 spike-reactive naïve B cells and pre-existing memory B cells contribute to antibody responses in unexposed individuals after vaccination.

Since December 2019, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has presented considerable public health challenges. Multiple vaccines have been used to induce neutralizing antibodies (nAbs) and memory B-cell responses against the viral spike (S) glycoprotein, and many essential epitopes have been defined. Previous reports have identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-reactive naïve B cells and preexisting memory B cells in unexposed individuals. However, the role of these spike-reactive B cells in vaccine-induced immunity remains unknown. To elucidate the characteristics of preexisting SARS-CoV-2 S-reactive B cells as well as their maturation after antigen encounter, we assessed the relationship of spike-reactive B cells before and after vaccination in unexposed human individuals. We further characterized the sequence identity, targeting domain, broad-spectrum binding activity and neutralizing activity of these SARS-CoV-2 S-reactive B cells by isolating monoclonal antibodies (mAbs) from these B cells. The frequencies of both spike-reactive naïve B cells and preexisting memory B cells before vaccination correlated with the frequencies of spike-reactive memory B cells after vaccination. Isolated mAbs from spike-reactive naïve B cells before vaccination had fewer somatic hypermutations (SHMs) than mAbs isolated from spike-reactive memory B cells before and after vaccination, but bound SARS-CoV-2 spike in vitro. Intriguingly, these germline-like mAbs possessed broad binding profiles for SARS-CoV-2 and its variants, although with low or no neutralizing capacity. According to tracking of the evolution of IGHV4-4/IGKV3-20 lineage antibodies from a single donor, the lineage underwent SHMs and developed increased binding activity after vaccination. Our findings suggest that spike-reactive naïve B cells can be expanded and matured by vaccination and cocontribute to vaccine-elicited antibody responses with preexisting memory B cells. Selectively and precisely targeting spike-reactive B cells by rational antigen design may provide a novel strategy for next-generation SARS-CoV-2 vaccine development.

Influence of the European Portuguese phonological system on the perception of close-mid and open-mid vowels

This study’s purpose was to analyse the influence of neutralisation on the perception of European Portuguese (EP) close-mid and open-mid vowels, and the gradient between the /i/, /e/, /ε/ and /a/ phonological categories. A fuzzy boundary between mid-vowels has been described in the phonological systems of various languages including EP, a variety of Portuguese with complex phonological phenomena and exceptional realisations of vowels in different contexts. Fifteen listeners from Lisbon participated in two tasks: Identification and goodness rating of 20 random repetitions of 31 stimuli from a /i/-/e/-/ε/-/a/ continuum. The boundaries between categories in the identification task, the internal structures of each category and the gradient of each boundary in the goodness rating task were analysed. Logistic regression was used to analyse the individual responses of listeners and the internal structure of phonemic categories, and prototypes were determined using bubble charts of goodness scores. The gradient of boundaries was analysed using two sets of data: X responses and goodness ratings. Models of the gradients of transition were developed using a mixed effects regression approach. Results from the identification task showed four vowel categories marked by three distinct boundaries. The stimulus with the highest score was approximately in the centroid and the goodness score decreased as the stimulus moved away from the centroid, which constitutes new evidence of an internal structure of the phonemic categories in EP. The main implications of the results obtained are for the description and typology of phonological phenomena in EP, supporting the existence of a non-partial contrast (which does not neutralise in any context) between /ε/ and /a/, and revealing less robust /i/-/e/ and /e/-/ε/ phonemic oppositions.

The role of new hepatitis B vaccines in South Africa.

Vaccination is key to eliminating hepatitis B virus infection in South Africa (SA). Despite introducing immunisation in 1995, as part of the expanded programme of immunisation (EPI), hepatitis B virus infection remains endemic, and EPI vaccine coverage is incomplete. In addition to infants, non-immune adults at risk of infection through their occupation or with behavioural risk factors should receive vaccination. SA has many individuals with diabetes mellitus (a prevalence of almost 13%), obesity, HIV (8.45 million) or older age (5 million >60 years old), associated with a poorer vaccine response. Recently two new hepatitis B vaccines have been licensed: HEPLISAV-B includes an adjuvant that improves immunogenicity and has shown improved vaccine response in individuals with HIV, old age or diabetes mellitus. PreHevbrio, which includes three hepatitis B surface protein domains, instead of one, may also be more immunogenic, although clinical study data are still limited. These two novel vaccines have not yet been investigated in children and licensed in SA. Should HEPLISAV-B become available in SA, it may be particularly valuable to target high-risk groups in the country, such as people living with HIV, who show a poor response to the currently licensed vaccine.

Life-Stage and Contextual Factors of Advance Care Planning Among Older Adults With Limited Income.

Patient perspectives are essential to understand healthcare disparities such as low rates of advance care planning (ACP) among adults with limited income. We completed twenty semi-structured interviews using purposive and snowball sampling. Initial and final themes emerged from inductive inclusion of recurring codes and deductive application of the cumulative disadvantage theory. Four themes emerged: (1) structural, (2) life-stage, (3) social stressors and resources, and (4) individual stress responses and ACP readiness. ACP resources among participants included positive structural and social support and previous familial death experiences that were mitigated by stress avoidance and competing priorities. Structural resources and healthcare stressors should be addressed with policy and research to improve continuous healthcare participation and support early, comprehensive ACP.

The Oddy Test and the Photographic Activity Test (PAT): A Direct Comparison of Accelerated Aging Test Methods for Assessing Storage, Display, and Transport Materials

ABSTRACT Two accelerated aging tests, the Oddy test and the Photographic Activity Test (PAT), are used to predict the safety of storage, display, or transport materials used near cultural heritage objects. Despite being designed to predict possible chemical damage for metallic and photographic objects, respectively, results from both tests are often applied toward other collection types. A direct comparison between the two tests was completed by evaluating the same set of thirty-five materials. Results indicated very little correlation between the tests, both when comparing overall results as well as on the level of individual detector responses. An additional comparison with the lead acetate test (LAT), a selective test for reduced sulfur compounds, provided further evidence that while the Oddy and PAT are reliable at predicting the effect of volatile gases on metals or reactions with materials in direct contact with photographs, respectively, they are responding to reactive species differently. The Oddy test and PAT are selective and sensitive, but each to different species and concentrations of reactive chemicals. The tests are most effective when applied toward the object types each was intended to mimic, and results from the two tests should neither be equated nor applied globally toward all collection types.

Hospital-based antimicrobial stewardship in Denmark, Greenland and the Faroe Islands – current landscape and barriers

ObjectivesTo describe the current organization and implementation of formalized, multidisciplinary hospital-based antimicrobial stewardship (AMS) structures in Denmark, the Faroe Islands, and Greenland. MethodsA structured electronic questionnaire was sent to all trainees and specialists in clinical microbiology (n=207) and infectious diseases (n=260), as well as clinical pharmacists (n=20) and paediatricians (n=10) with expertise in infectious diseases.The survey had 30 multiple-choice, rating-scale, and open-ended questions based on an international consensus checklist for hospital AMS, adapted to a Danish context. ResultsOverall, 145 individual responses representing 20 hospitals were received. Nine hospitals (45%) reported a formal AMS-strategy, eight (40%) a formal organizational multidisciplinary structure and a multidisciplinary AMS-team, and six (30%) a designated professional as a leader of the AMS-team. A majority of hospitals reported access to updated guidelines (80%) and regularly monitored and reported the quantity of antibiotics prescribed (70% and 65%, respectively). Only one hospital (5%) reported a dedicated, sustainable, and sufficient AMS-budget, three hospitals (15%) audited courses of therapy for specific agents/clinical conditions and four hospitals (20%) had a document clearly defining roles, procedures of collaboration and responsibilities for AMS. A total of 42% of all individual respondents had received formal AMS-training. Main barriers were a lack of financial resources (52%), a lack of mandate from the hospital management (30%), and AMS not being a priority (18%). ConclusionsCore elements important for multidisciplinary hospital-based AMS can be strengthened in Danish hospitals. Funding, clear mandates, prioritization from the hospital management, and the implementation of multidisciplinary AMS-structures may help close the identified gaps.

StressME: Unified computing framework of Escherichia coli metabolism, gene expression, and stress responses.

Generalist microbes have adapted to a multitude of environmental stresses through their integrated stress response system. Individual stress responses have been quantified by E. coli metabolism and expression (ME) models under thermal, oxidative and acid stress, respectively. However, the systematic quantification of cross-stress & cross-talk among these stress responses remains lacking. Here, we present StressME: the unified stress response model of E. coli combining thermal (FoldME), oxidative (OxidizeME) and acid (AcidifyME) stress responses. StressME is the most up to date ME model for E. coli and it reproduces all published single-stress ME models. Additionally, it includes refined rate constants to improve prediction accuracy for wild-type and stress-evolved strains. StressME revealed certain optimal proteome allocation strategies associated with cross-stress and cross-talk responses. These stress-optimal proteomes were shaped by trade-offs between protective vs. metabolic enzymes; cytoplasmic vs. periplasmic chaperones; and expression of stress-specific proteins. As StressME is tuned to compute metabolic and gene expression responses under mild acid, oxidative, and thermal stresses, it is useful for engineering and health applications. The modular design of our open-source package also facilitates model expansion (e.g., to new stress mechanisms) by the computational biology community.

Infiltration of CD3+ and CD8+ lymphocytes in association with inflammation and survival in pancreatic cancer.

Pancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins. Tissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples. Our findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC. In this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.

TREG cells and CXCR3+ circulating TFH cells concordantly shape the neutralizing antibody responses in individuals who have recovered from mild COVID-19.

Regulatory T (TREG) cells are involved in the antiviral immune response in patients with COVID-19; however, whether TREG cells are involved in the neutralizing antibody (nAb) response remains unclear. Here, we found that individuals who recovered from mild but not severe COVID-19 had significantly greater frequencies of TREG cells and lower frequencies of CXCR3+ circulating TFH (cTFH) cells than healthy controls. Furthermore, TREG and CXCR3+ cTFH cells were negatively and positively correlated with the nAb responses, respectively, and TREG cells was inversely associated with CXCR3+ cTFH cells in individuals who recovered from mild COVID-19 but not in those with severe disease. Mechanistically, TREG cells inhibited memory B-cell differentiation and antibody production by limiting the activation and proliferation of cTFH cells, especially CXCR3+ cTFH cells, and functional molecule expression. This study provides novel insight showing that mild COVID-19 elicits a concerted nAb responses which are shaped by both TREG and TFH cells.

Functional brain responses to emotional faces after three to five weeks of intake of escitalopram in healthy individuals: a double-blind, placebo-controlled randomised study

Short-term intake of selective serotonin reuptake inhibitors (SSRIs) modulates threat-related amygdala responses in healthy individuals. However, how SSRI intake over a clinically relevant time period modulates threat-related amygdala responses is less clear. In a semi-randomised, double-blind, placebo-controlled study of 64 healthy individuals (SSRI n = 32, placebo n = 32), we examined the effect of 3–5 weeks of SSRI escitalopram (20 mg daily) on brain response to angry, fearful and neutral faces using BOLD fMRI. Data was analysed using a whole-brain region-wise approach extracting standardised effects (i.e., Cohen’s D). The study was conducted at the Copenhagen University Hospital. A priori, we hypothesised that SSRI would attenuate amygdala responses to angry and fearful faces but not to neutral ones. Whether SSRI modulates correlations between amygdala responses to emotional faces and negative mood states was also explored. Compared to placebo, 3–5 weeks of SSRI intake did not significantly affect the amygdala response to angry, fearful, or neutral faces (|Cohen’s D|< 0.2, PFWER = 1). Whole-brain, region-wise analyses revealed significant differences in frontal (|Cohen’s D|< 0.6, PFWER < .01) and occipital regions (|Cohen’s D|< 0.5, PFWER < .01). SSRI did not modulate correlations between amygdala responses to emotional faces and negative mood states. Our findings indicate that a 3–5 week SSRI intake impacts cortical responses to emotional stimuli, an effect possibly involved in SSRI’s therapeutic efficacy.Trial registration Clinical Trials NCT04239339.

503 - Visualizing 3-year treatment outcome trajectories of dupilumab in adults with moderate-to-severe atopic dermatitis in real world practice

Abstract Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with high global prevalence and profound negative impact on the quality of life of children and adults. RELIEVE-AD, a prospective, longitudinal cohort study, included adults with moderate-to-severe AD who initiated dupilumab in real-world clinical practice. Results from RELIEVE-AD showed significant improvements in patient-reported disease control, quality of life, and treatment satisfaction in the overall study population that were sustained through 3 years of dupilumab treatment. Objective To report on response to dupilumab treatment over time at the individual patient-level in adults with moderate-to-­severe AD, using 3-year data from RELIEVE-AD. Methods RELIEVE-AD is a single-arm, prospective, observational study of adults with moderate-to-severe AD prescribed dupilumab and enrolled in the US dupilumab patient support program, who agreed to participate in online surveys at baseline and Months 1, 2, 3, 6, 9, 12, and 30–36. Post hoc analysis of the RELIEVE-AD 3yr data, describing changes from baseline through all post-dupilumab initiation time points at individual patient level, using Sankey plots to assess variability of individual patient response over time for the following patient-reported outcomes: Atopic Dermatitis Control Tool (ADCT) total score-based disease control status, AD-related health status, and AD treatment satisfaction. Results Of 698 patients who completed the baseline survey, 425 completed the Months 30–36 survey. Disease control (as measured by the ADCT) increased rapidly from 5.9% at baseline to 61.0% at Month 1, further increasing to 80.7% at Months 30–36. Patients reported improved AD-related health status at Month 30–36, with 70.9% reporting “Excellent” or “Very Good”, compared to 2.8% at baseline. At Months 30–36, 86.8% of patients reported being “Extremely Satisfied/Very Satisfied/Somewhat Satisfied” with their AD treatment, compared to 17.7% at baseline. All endpoints were significant vs baseline (P &amp;lt; 0.001). Sankey plots of the three outcomes indicated that the majority of patients maintained response over time after achieving the initial response. Conclusion The majority of patients who completed the survey reported benefits of dupilumab, such as AD control, treatment satisfaction, and health status, which remained stable or significantly improved during long-term treatment up to 36 months.

Effects of dietary fibre on metabolic health and obesity.

Obesity and metabolic syndrome represent a growing epidemic worldwide. Body weight is regulated through complex interactions between hormonal, neural and metabolic pathways and is influenced by numerous environmental factors. Imbalances between energy intake and expenditure can occur due to several factors, including alterations in eating behaviours, abnormal satiation and satiety, and low energy expenditure. The gut microbiota profoundly affects all aspects of energy homeostasis through diverse mechanisms involving effects on mucosal and systemic immune, hormonal and neural systems. The benefits of dietary fibre on metabolism and obesity have been demonstrated through mechanistic studies and clinical trials, but many questions remain as to how different fibres are best utilized in managing obesity. In this Review, we discuss the physiochemical properties of different fibres, current findings on how fibre and the gut microbiota interact to regulate body weight homeostasis, and knowledge gaps related to using dietary fibres as a complementary strategy. Precision medicine approaches that utilize baseline microbiota and clinical characteristics to predict individual responses to fibre supplementation represent a new paradigm with great potential to enhance weight management efficacy, but many challenges remain before these approaches can be fully implemented.