Subsequent Time Research Articles

Estrogenic control of reward prediction errors and reinforcement learning.

Gonadal hormones act throughout the brain 1 , and neuropsychiatric disorders vary in symptom severity over the reproductive cycle, pregnancy, and perimenopause 2-4 . Yet how hormones influence cognitive processes is unclear. Exogenous 17 β -estradiol modulates dopamine signaling in the nucleus accumbens core (NAcc) 5,6 , which instantiates reward prediction errors (RPEs) for reinforcement learning 7-16 . Here we show that endogenous 17 β -estradiol enhances RPEs and sensitivity to previous rewards by reducing dopamine reuptake proteins in the NAcc. Rats performed a task with different reward states; they adjusted how quickly they initiated trials across states, balancing effort against expected rewards. NAcc dopamine reflected RPEs that predicted and causally influenced initiation times. Elevated endogenous 17 β -estradiol increased sensitivity to reward states by enhancing dopaminergic RPEs in the NAcc. Proteomics revealed reduced dopamine transporter expression. Finally, knockdown of midbrain estrogen receptors suppressed reinforcement learning. 17 β -estradiol therefore controls RPEs via dopamine reuptake, mechanistically revealing how hormones influence neural dynamics for motivation and learning.

Flexible CO2 Laser in Therapeutic Bronchoscopy: Initial Experiences in a Tertiary Center.

CO2 Laser (CO2L) technology deployable through flexible endoscopes now allows for their use throughout the airway, although published data are limited. Retrospective analysis of CO2L bronchoscopic procedures, excluding glottic and subglottic interventions. Procedural success was defined as >50% visual reduction in airway obstruction in the area treated or resolution of the procedural indication. Seventy-two procedures were performed on 36 patients. Nonmalignant indications comprised 66%: stent-associated granulation tissue (28%), granulomatosis with polyangiitis lesions (23%), and lung transplant-related granulation tissue (16%) were the most common. Bronchoscopic access was flexible only in 81% and primarily rigid (combined with flexible) in 18%. The site of intervention was the trachea at 19%, the mainstem at 56%, and lobar/segmental airways at 45%. Procedural success was 89%. CO2L was used exclusively in 19%; in 81%, additional techniques were required, most commonly balloon dilation (59%), cryo-debulking (23%), and rigid dilation (16%). Malignant indications had a nonsignificant trend toward requiring adjuvant techniques ( P =0.05). Seventy-six percent of the patients required more than 1 procedure. CO2L exclusive cases had no statistically different needs for subsequent therapeutic bronchoscopies ( P =0.10) or time to reintervention (109 vs. 41 days, P =0.07), and reintervention-free survival was similar ( P =0.10) and difficult to predict. The complication rate attributable to CO2L was 2.7%. CO2L is a safe and useful tool when precise cutting and vaporization are desired. Its use in multi-modality approaches has high levels of success in adequately selected lesions, adding an ablative potential to dilation techniques. Vasculitis-associated scars/webs and granulation tissue (including stent-associated) appear to be ideal targets.

Excremental mobilities and minimal technopolitics: Toilets, race, and expulsion in Tanzania

ABSTRACT Centreing an everyday form of human expulsion – defecation – this article demonstrates that toilets produced colonial racial orders in colonial Tanzania through the different excremental mobilities their materialities allowed, including both movement and immobility. It specifically argues that colonial pit toilets affixed excrement to African spaces and helped create a form of minimal technopolitics that expelled infrastructural possibilities from subsequent time periods.

115 Solubility and degradation of human fertility-promoting molecules in a rumen environment

Abstract Endometrial epithelial of cows conceiving was associated to gene set enrichment of pathways associated to synthesis, metabolism, and degradation of myo-inositol pathways (Physiol. Genomics 54: 71-85, 2022). Progesterone-modulated transcription also indicated an increase in oxidative phosphorylation pathways in the endometrial epithelial of cows. Thus, modulation of myo-inositol and oxidative phosphorylation pathways can favor conception rates in cattle. Oral supplementation with pyrroloquinoline Quinone (PQQ), an antioxidant, and inositol isomers (myo- and D-chiro-inositol) has been proven to be beneficial for fertility of women undergoing assisted reproductive biotechnologies. However, oral supplementation of these compounds to ruminant species has not been evaluated. It is unknown if PQQ and inositol isomers are soluble in the rumen environment, if they are degraded by the microbial populations which exist in this environment, or the timeframe for the ruminal degradation of these molecules resulting from oral supplementation. The objectives of this study were to 1) evaluate disappearance (solubility) of different of inositol isomers and PQQ; and 2) to quantify the in-vitro ruminal degradability of inositol isomers and PQQ over time. Inositol isomers and PQQ (0.25 g) were placed in Ankom bags and heat sealed. The bags were placed in glass beakers with an artificial saliva solution and rumen fluid, then incubated at 39 C in a warm shaker bath to simulate ruminal digestion for 0, 1, 2, 4, 8, 12, 24, and 48 h. These were then evaluated for disappearance of each form of inositol from the Ankom bag and repeated for a total of five replicates. For the second trial, only myo-inositol was evaluated. In addition to bag removal at the same time points, duplicate ruminal fluid samples were collected for myo-inositol concentration determination. This trial had seven replicates. For all forms of inositol 0.00% was removed at 0 h, and by 1 h 99.0 % inositol had disappeared (P > 0.05). There were two exceptions, PQQ, at 1 h was less (P < 0.0001; 96.33 %) and at 4 h (98.46 %). For the second trial, myo-inositol disappearance increased (P = 0.0001) from 0.00 % at 1 h to 99.53 % at 4 h and remained constant (P > 0.05) for subsequent sampling times. Ruminal fluid concentration of myo-inositol increased (P < 0.0001) from 0.197 to 5.39 g/L, and remained constant (P > 0.05) until h 24 when it had decreased (P < 0.0001) to 2.766 g/L, and decreased P < 0.0001) further by 48 h to 0.377 g/L. Ruminal concentration of myo-inositol was not different (P > 0.05) between 0 h and 48 h. These data indicates that inositol isomers and PQQ are soluble in the rumen environment, though not immediately, with myo-inositol concentrations peaking between 12 and 24 h and disappearing mostly by h 48.

Association between blood markers and the progression of osseointegration in percutaneous prostheses patients-A pilot study.

Patients implanted with osseointegrated (OI) prosthetic systems have reported vastly improved upper and lower extremity prosthetic function compared with their previous experience with socket-suspension systems. However, OI systems have been associated with superficial and deep-bone infections and implant loosening due, in part, to a failure of the osseointegration process. Although monitoring the osseointegration using circulating biomarkers has clinical relevance for understanding the progression of osseointegration with these devices, it has yet to be established. Ten patients were enrolled in this study. Blood samples were collected at pre-selected times, starting before implantation surgery, and continuing to 12 months after the second surgery. Bone formation markers, bone resorption markers, and circulating amino acids were measured from blood samples. A linear mixed model was generated for each marker, incorporating patient ID and age with the normalized marker value as the response variable. Post hoc comparisons were made between 1 week before Stage 1 Surgery and all subsequent time points for each marker, followed by multiple testing corrections. Serial radiographic imaging of the residual limb containing the implant was obtained during follow-up, and the cortical index (CI) was calculated for the bone at the porous region of the device. Two markers of bone formation, specifically bone-specific alkaline phosphatase (Bone-ALP) and amino-terminal propeptide of type I procollagen (PINP), exhibited significant increases when compared with the baseline levels of unloaded residual bone prior to the initial surgery, and they subsequently returned to their baseline levels by the 12-month mark. Patients who experienced clinically robust osseointegration experienced increased cortical bone thickness at the porous coated region of the device. A medium correlation was observed between Bone-ALP and the porous CI values up to PoS2-M1 (p = .056), while no correlation was observed for PINP. An increase in bone formation markers and the lack of change observed in bone resorption markers likely reflect increased cortical bone formation induced by the end-loading design of the Utah OI device used in this study. A more extensive study is required to validate the correlation observed between Bone-ALP and porous CI values.

Model-based monocular 6-degree-of-freedom pose tracking for asteroid

In this paper, we present a novel vision-based framework to track the 6-DoF pose of an asteroid in real time with the 3D contour of the asteroid as a feature. During pose tracking, at the beginning time of tracking, the tracking system is initialized by a pose retrieval method. At each subsequent time instant, given the 3D mesh model of an asteroid, with the initial pose and its covariance given by the square root cubature Kalman Filter (SCKF), the 3D mesh segments constituting the 3D asteroid contour are efficiently extracted from the 3D mesh model. Then, in the input asteroid image, we search the image points corresponding to the extracted 3D segments within the searching range defined by the initial pose and its covariance. After that, the asteroid pose is determined in real time by minimizing the angles between the back-projection lines of the searched image points and the projection planes of the corresponding 3D segments, which is much more robust to the position change of the asteroid and asteroid size. The covariance matrix of the pose is inferred from the Cartesian noise model in the first order. Eventually, the SCKF is derived from the second-order auto regression to generate the final pose estimate and give the initial pose and its covariance for the next time instant. The synthetic trials quantitatively validate the real-time performance, robustness, and accuracy of our algorithm in dark space, different imaging distances, lighting conditions, image noise, model error, and initial pose error, and meanwhile, the real trial qualitatively shows the effectiveness of our method.

Religiosity, Aging in the Homeland, and Growing Old in the Diaspora: A Longitudinal Study of Two Cohorts of Indian Older Adults.

This article reports a longitudinal study comparing religiosity among two cohorts of Indian older adults-those who age in the homeland of India (AIH cohort) and immigrants (to the USA) or diaspora older adults (DOA). Results indicated that AIH and DOA cohorts' religiosity outcomes were comparable at baseline but there was a statistically significant increase in all outcomes of the DOA cohort at subsequent time points. Women and single older adults in both the cohorts had higher religiosity scores at baseline. Religiosity scores were higher among those in the DOA cohort who migrated following marital disruption (widowhood, divorce) or grandchild birth and lived with adult immigrant children and their families. The immigration process can have an impact on religious orientation of older adults and place is a significant variable impacting religiosity possibly for augmenting the sense of self, acquire social capital and preserve cultural identity in the foreign land.

Efficacy of 38% silver diamine fluoride in reducing gingival inflammation and plaque accumulation in older adults living in retirement-homes: A randomized controlled pilot trial

ObjectivesEmerging from earlier case reports the potential benefits of 38 % silver diamine fluoride (SDF) in addressing pathogenic biofilms and mitigating gingival inflammation and enlargement have sparked interest. Our study aimed to evaluate the efficacy of 38 % SDF in reducing gingival inflammation and plaque accumulation in older adults living in retirement-homes. MethodsThis 7-week randomized, controlled, double-blinded pilot trial employed a parallel assignment design. The study enrolled older adults (aged ≥65) residing in retirement homes in Dallas County, ultimately comprising a cohort of 40 participants who were evenly divided into two arms. The experimental group received SDF treatment, whereas the comparator group received a placebo. Over three consecutive weeks, both groups had solutions applied to the facial surfaces of all their teeth once per week. The primary outcomes measured the change in Löe-Silness Gingival Index (GI) and Silness-Löe Plaque Index (PI) at 7 weeks following baseline treatment. Repeated measures ANOVA was utilized to assess changes over time within each group (n = 15 each). Post-hoc paired t-tests were conducted to compare changes between week 1 and each subsequent follow-up time point (weeks 3, 5, 7), supplemented with 95 % confidence intervals for change from week 1. ResultsIn the SDF group, within-group comparisons demonstrated significant reductions (adjusted p < .05) in GI scores within 3 weeks (-.93±.37), as opposed to week 1 (1.90±.39). Between-group comparisons unveiled reductions in both mean GI (p < .05) and PI (p < .05), indicating less gingival inflammation and plaque accumulation in the SDF group at all time points, commencing at week 3. ConclusionsThis study showed that 38 % SDF was effective in reducing gingival inflammation and plaque accumulation in older adults living in retirement-homes. Clinical significanceOral health in older adults is a public health concern, especially for the medically compromised or those without traditional care. Our findings offer hope for enhancing oral health quality of life by introducing a cost-effective, compliance-free, noninvasive, and accessible therapeutic. Trial registrationNCT03445286.(clinicaltrials.gov)

Predicting long-term time to cardiovascular incidents using myocardial perfusion imaging and deep convolutional neural networks

Myocardial perfusion imaging (MPI) is a clinical tool which can assess the heart's perfusion status, thereby revealing impairments in patients' cardiac function. Within the MPI modality, the acquired three-dimensional signals are typically represented as a sequence of two-dimensional grayscale tomographic images. Here, we proposed an end-to-end survival training approach for processing gray-scale MPI tomograms to generate a risk score which reflects subsequent time to cardiovascular incidents, including cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke (collectively known as Major Adverse Cardiovascular Events; MACE) as well as Congestive Heart Failure (CHF). We recruited a total of 1928 patients who had undergone MPI followed by coronary interventions. Among them, 80% (n = 1540) were randomly reserved for the training and 5- fold cross-validation stage, while 20% (n = 388) were set aside for the testing stage. The end-to-end survival training can converge well in generating effective AI models via the fivefold cross-validation approach with 1540 patients. When a candidate model is evaluated using independent images, the model can stratify patients into below-median-risk (n = 194) and above-median-risk (n = 194) groups, the corresponding survival curves of the two groups have significant difference (P < 0.0001). We further stratify the above-median-risk group to the quartile 3 and 4 group (n = 97 each), and the three patient strata, referred to as the high, intermediate and low risk groups respectively, manifest statistically significant difference. Notably, the 5-year cardiovascular incident rate is less than 5% in the low-risk group (accounting for 50% of all patients), while the rate is nearly 40% in the high-risk group (accounting for 25% of all patients). Evaluation of patient subgroups revealed stronger effect size in patients with three blocked arteries (Hazard ratio [HR]: 18.377, 95% CI 3.719–90.801, p < 0.001), followed by those with two blocked vessels at HR 7.484 (95% CI 1.858–30.150; p = 0.005). Regarding stent placement, patients with a single stent displayed a HR of 4.410 (95% CI 1.399–13.904; p = 0.011). Patients with two stents show a HR of 10.699 (95% CI 2.262–50.601; p = 0.003), escalating notably to a HR of 57.446 (95% CI 1.922–1717.207; p = 0.019) for patients with three or more stents, indicating a substantial relationship between the disease severity and the predictive capability of the AI for subsequent cardiovascular inciidents. The success of the MPI AI model in stratifying patients into subgroups with distinct time-to-cardiovascular incidents demonstrated the feasibility of proposed end-to-end survival training approach.

Toward Standardized Aerovirology: A Critical Review of Existing Results and Methodologies.

Understanding the airborne survival of viruses is important for public health and epidemiological modeling and potentially to develop mitigation strategies to minimize the transmission of airborne pathogens. Laboratory experiments typically involve investigating the effects of environmental parameters on the viability or infectivity of a target airborne virus. However, conflicting results among studies are common. Herein, the results of 34 aerovirology studies were compared to identify links between environmental and compositional effects on the viability of airborne viruses. While the specific experimental apparatus was not a factor in variability between reported results, it was determined that the experimental procedure was a major factor that contributed to discrepancies in results. The most significant contributor to variability between studies was poorly defined initial viable virus concentration in the aerosol phase, causing many studies to not measure the rapid inactivation, which occurs quickly after particle generation, leading to conflicting results. Consistently, studies that measured their reference airborne viability minutes after aerosolization reported higher viability at subsequent times, which indicates that there is an initial loss of viability which is not captured in these studies. The composition of the particles which carry the viruses was also found to be important in the viability of airborne viruses; however, the mechanisms for this effect are unknown. Temperature was found to be important for aerosol-phase viability, but there is a lack of experiments that directly compare the effects of temperature in the aerosol phase and the bulk phase. There is a need for repeated measurements between different research groups under identical conditions both to assess the degree of variability between studies and also to attempt to better understand already published data. Lack of experimental standardization has hindered the ability to quantify the differences between studies, for which we provide recommendations for future studies. These recommendations are as follows: measuring the reference airborne viability using the "direct method"; use equipment which maximizes time resolution; quantify all losses appropriately; perform, at least, a 5- and 10-min sample, if possible; report clearly the composition of the virus suspension; measure the composition of the gas throughout the experiment. Implementing these recommendations will address the most significant oversights in the existing literature and produce data which can more easily be quantitatively compared.

Physical aging and vitrification in polymers and other glasses: Complex behavior and size effects

AbstractThe paradigmatic view on the transformation of a supercooled liquid into a glass, so‐called vitrification or glass transition, and the subsequent time evolution of the non‐equilibrium glass, addressed as physical aging, relies on the exclusive role of the main relaxation with super‐Arrhenius temperature dependence. The aim of the present review is to carefully scrutinize the wealth of recent experimental results, above all in polymeric glasses, showing the relevance of other relaxational mechanisms in both vitrification and physical aging. While the relaxation bears dominant role in both phenomena in proximity of the glass transition temperature, , a broad view on a much wider temperature range indicates that vitrification and physical aging are mediated by non‐ mechanisms of equilibration. This review also shows that a reduction of the typical time scale of equilibration can be achieved in glasses with large free interface, namely with reduced sample size. In this way, fast non‐ mechanisms of equilibration can be exploited to convey glasses to low energy states in experimentally feasible time scales, thereby attaining information on the existence of the so‐called “ideal glass” in small sized samples.

Advanced imaging use and delays among inpatients with psychiatric comorbidity.

To determine whether presence of a psychiatric comorbidity impacts use of inpatient imaging tests and subsequent wait times. This was a retrospective cohort study of all patients admitted to General Internal Medicine (GIM) at five academic hospitals in Toronto, Ontario from 2010 to 2019. Exposure was presence of a coded psychiatric comorbidity on admission. Primary outcome was time to test, as calculated from the time of test ordering to time of test completion, for computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, or peripherally inserted central catheter (PICC) insertion. Multilevel mixed-effects models were used to identify predictors of time to test, and marginal effects were used to calculate differences in absolute units (h). Secondary outcome was the rate of each type of test included. Subgroup analyses were performed according to type of psychiatric comorbidity: psychotic, mood/anxiety, or substance use disorder. There were 196,819 GIM admissions from 2010to 2019.In 77,562 admissions, ≥1 advanced imaging test was performed. After adjusting for all covariates, presence of any psychiatric comorbidity was associated with increased time to test for MRI (adjusted difference: 5.3h, 95% confidence interval [CI]: 3.9-6.8), PICC (adjusted difference: 3.7h, 95% CI: 1.6-5.8), and ultrasound (adjusted difference: 3.0h, 95% CI: 2.3-3.8), but not for CT (adjusted difference: 0.1h, 95% CI: -0.3 to 0.5). Presence of any psychiatric comorbidity was associated with lower rate of ordering for all test types (adjusted difference: -17.2 tests per 100days hospitalization, interquartile range: -18.0 to -16.3). There was a lower rate of ordering of advanced imaging among patients with psychiatric comorbidity. Once ordered, time to test completion was longer for MRI, ultrasound, and PICC. Further exploration, such as quantifying rates of cancelled tests and qualitative studies evaluating hospital, provider, and patient barriers to timely advanced imaging, will be helpful in elucidating causes for these disparities.

ACERAC: Efficient Reinforcement Learning in Fine Time Discretization.

One of the main goals of reinforcement learning (RL) is to provide a way for physical machines to learn optimal behavior instead of being programmed. However, effective control of the machines usually requires fine time discretization. The most common RL methods apply independent random elements to each action, which is not suitable in that setting. It is not feasible because it causes the controlled system to jerk and does not ensure sufficient exploration since a single action is not long enough to create a significant experience that could be translated into policy improvement. In our view, these are the main obstacles that prevent the application of RL in contemporary control systems. To address these pitfalls, in this article, we introduce an RL framework and adequate analytical tools for actions that may be stochastically dependent in subsequent time instances. We also introduce an RL algorithm that approximately optimizes a policy that produces such actions. It applies experience replay (ER) to adjust the likelihood of sequences of previous actions to optimize expected n -step returns that the policy yields. The efficiency of this algorithm is verified against four other RL methods [continuous deep advantage updating (CDAU), proximal policy optimization (PPO), soft actor-critic (SAC), and actor-critic with ER (ACER)] in four simulated learning control problems (Ant, HalfCheetah, Hopper, and Walker2D) in diverse time discretization. The algorithm introduced here outperforms the competitors in most cases considered.

Evaluation of Dynamic Effects of Depressive Symptoms on Physical Function in Knee Osteoarthritis.

To assess how changes in depressive symptoms influence physical function over time among those with radiographic knee osteoarthritis (OA). Participants from the Osteoarthritis Initiative with radiographic knee OA (n=2,212) and complete data were identified at baseline. Depressive symptoms were assessed as a time-varying score at baseline and the first three annual follow-up visits using the Center for Epidemiological Studies Depression Scale (CES-D) Scale. Physical function was measured at the first four follow-up visits using 20-meter gait speed meters per second. The following two marginal structural models were fit: one assessing the main effect of depressive symptoms on gait speed and another assessing time-specific associations. Time-adjusted results indicated that higher CES-D scores were significantly associated with slower gait speed (-0.0048; 95% confidence interval -0.0082 to -0.0014), and time-specific associations of CES-D were largest during the first follow-up interval (-0.0082; 95% confidence interval -0.0128 to -0.0035). During subsequent follow-up time points, the influence of depressive symptoms on gait speed diminished. The negative effect of depressive symptoms on physical function may decrease over time as knee OA progresses.

Beta rebound reduces subsequent movement preparation time by modulating of GABAA inhibition.

Post-movement beta synchronization is an increase of beta power relative to baseline, which commonly used to represent the status quo of the motor system. However, its functional role to the subsequent voluntary motor output and potential electrophysiological significance remain largely unknown. Here, we examined the reaction time of a Go/No-Go task of index finger tapping which performed at the phases of power baseline and post-movement beta synchronization peak induced by index finger abduction movements at different speeds (ballistic/self-paced) in 13 healthy subjects. We found a correlation between the post-movement beta synchronization and reaction time that larger post-movement beta synchronization prolonged the reaction time during Go trials. To probe the electrophysiological significance of post-movement beta synchronization, we assessed intracortical inhibitory measures probably involving GABAB (long-interval intracortical inhibition) and GABAA (short-interval intracortical inhibition) receptors in beta baseline and post-movement beta synchronization peak induced by index finger abduction movements at different speeds. We found that short-interval intracortical inhibition but not long-interval intracortical inhibition increased in post-movement beta synchronization peak compared with that in the power baseline, and was negatively correlated with the change of post-movement beta synchronization peak value. These novel findings indicate that the post-movement beta synchronization is related to forward model updating, with high beta rebound predicting longer time for the preparation of subsequent movement by inhibitory neural pathways of GABAA.

Methodology of generation of CFD meshes and 4D shape reconstruction of coronary arteries from patient-specific dynamic CT

Due to the difficulties in retrieving both the time-dependent shapes of the vessels and the generation of numerical meshes for such cases, most of the simulations of blood flow in the cardiac arteries use static geometry. The article describes a methodology for generating a sequence of time-dependent 3D shapes based on images of different resolutions and qualities acquired from ECG-gated coronary artery CT angiography. The precision of the shape restoration method has been validated using an independent technique. The original proposed approach also generates for each of the retrieved vessel shapes a numerical mesh of the same topology (connectivity matrix), greatly simplifying the CFD blood flow simulations. This feature is of significant importance in practical CFD simulations, as it gives the possibility of using the mesh-morphing utility, minimizing the computation time and the need of interpolation between boundary meshes at subsequent time instants. The developed technique can be applied to generate numerical meshes in arteries and other organs whose shapes change over time. It is applicable to medical images produced by other than angio-CT modalities.

DOP74 Short and long-term effectiveness and safety of ustekinumab in Ulcerative Colitis in real life: the ULISES study

Abstract Background Primary aim: To assess the durability of ustekinumab treatment in patients with ulcerative colitis (UC). Secondary aims: To assess the short-term effectiveness, the durability of response, and the tolerability of ustekinumab in clinical practice. Methods Retrospective, multicenter study including UC patients who had received the 1st ustekinumab dose at least 16 weeks before inclusion. Patients were followed-up from the 1st ustekinumab dose to treatment discontinuation or last visit. Only patients with active disease [Partial Mayo Score (PMS)&amp;gt;2] at ustekinumab start were considered in the effectiveness analysis. Clinical effectiveness was based on PMS. Patients who stopped ustekinumab before their last visit were considered not in remission at subsequent time points (negative imputation). Results 620 patients were included (table 1). 78% of patients who started ustekinumab maintenance treatment, did it with 90 mg every-8-weeks dose. 155 patients (25%) withdrew ustekinumab during follow-up [median=12 months (m)]. Incidence rate of ustekinumab discontinuation was 20% per patient-year of follow-up. The probability of maintaining ustekinumab is shown in figure 1A. Among patients who withdrew ustekinumab, the main reasons were primary non-response (39%) and loss of response (35%). Anaemia at baseline (HR=1.5, 95%CI=1.1-2.1), steroids at baseline (HR=1.5; 95%CI=1.06-2.08), and more severe clinical activity at baseline (HR=1.5; 95%CI=1.09-2.06) were associated with higher risk of ustekinumab discontinuation. Short and long-term effectiveness of ustekinumab is shown on figure 1B. Moderate-severe vs. mild disease activity at baseline (OR=0.3, 95%CI=0.2-0.5), male sex (OR=0.5; 95%CI=0.4-0.8), and increased number of previous biologics (OR=0.6, 95%CI=0.6-0.8) were associated with lower likelihood of steroid-free remission at week 16. A total of 57 (25%) patients among those with active disease at baseline and with steroid-free remission at week 16, lost response during a median follow-up of 8 m (IQR=3-16 m) (figure 1C). The dose was escalated in 72% of patients with loss of response, and 80% improved (67% remission); an intravenous reinduction was given in 3 patients, and none of them improved. A total of 176 patients (28%) had at least one adverse event, with infections being the most frequent (11%). No negative impact on extraintestinal manifestations and/or immunomediated diseases was seen. Conclusion Ustekinumab was effective in inducing remission even in highly refractory UC patients. A proportion of patients discontinue the treatment, mostly due to primary failure and loss of response. Dose escalation may be effective to regain response after loss of effectiveness. The safety profile was similar to previously reported.

Number of subsequent treatments and time to recurrence in hepatocellular carcinoma.

526 Background: Hepatocellular carcinoma (HCC) is often managed with locoregional therapies including surgical resection, ablation, transcatheter arterial chemoembolization (TACE), and selective internal radiation therapy (Y90). Most patients require multiple treatments over several years due to ongoing development of new lesions, distinct from other cancer types. Our project aims to analyze this treatment trajectory and the impact of treatment selection. Here we present an interim analysis focusing on the number of subsequent therapies and time to first recurrence (TTR). Methods: We identified 202 patients newly diagnosed with HCC between 2019-2021 who were seen in the BIDMC Liver Tumor Multidisciplinary Clinic. Complete abstraction of medical records was performed in 51 patients to date. Our primary outcome was of the number of subsequent therapies depending on the selected first-line locoregional therapy. Incidence risk ratios (IRR) were obtained via a crude and adjusted (age, gender, race, Child Pugh) linear regression model. Ablation was used as the reference treatment. Secondary outcomes included survival analysis of TTR, overall survival (OS) and time to initiation of systemic therapy. TTR was defined as the appearance of new lesions, excluding residual disease. Results: Mean age at diagnosis was 65 years old, 73% were male, and 92% ECOG 0. 37 patients out of 50 had recurrence, almost all local (97%). The total number of subsequent therapies received was 110; the most common treatment received on first recurrence was ablation (59%) followed by Y90 (24%). Patients who received TACE were more likely to undergo a higher number of subsequent therapies in both the unadjusted (IRR 2.51, p&lt;0.001, 95%CI 1.6-3.9) and adjusted analysis (IRR 4.43 p&lt;0.001, 95%CI 2.5-8.1) with 4.4 (2-9) mean subsequent treatments when compared to ablation with a mean number of subsequent treatments of 1.47 (0-7). Y90 had 1.85 (0-7) mean subsequent treatments and surgery 1.87 (0-7), with inconclusive results regarding IRR when compared to ablation. Median TTR was 19.1 months (10.2-29.3) with ablation having the longest time with 22.2 months (13.2-31.1), followed by surgery with 20.3 months (13.3-29.3), Y90 with 19.1 months (6-NR) and TACE with 12.1 (6.1-21.2). Median OS was not reached, and only 5 patients started systemic therapy. Conclusions: This interim analysis shows that patients treated with TACE as the first locoregional therapy are likely to undergo a higher number of subsequent treatments when compared to ablation.

Physical activity, recreational screen time, and depressive symptoms among Chinese children and adolescents: a three-wave cross-lagged study during the COVID-19 pandemic

BackgroundLongitudinal evidence is lacking on the interplay between lifestyle behaviors and depressive symptoms, especially in the context of the COVID-19 pandemic. This study investigated the changes in physical activity and recreational screen time during the pandemic, along with their reciprocal associations with depressive symptoms among children and adolescents.MethodsThe public health emergency due to the pandemic started in January 2023 and lasted for two months in Shanghai, China. A three-wave longitudinal study was conducted among 1,666 children and adolescents (6–18 years) in January, March, and July 2023. Moderate-to-vigorous intensity physical activity (MVPA), recreational screen time, and depressive symptoms were measured using self-reported questionnaires. Random-intercept cross-lagged panel models were constructed to examine the bidirectional associations between physical activity and recreational screen time with depressive symptoms.ResultsChildren and adolescents experienced a significant decrease in MVPA and a substantial increase in recreational screen time during the pandemic, which failed to return to pre-pandemic levels post-pandemic. Pre-pandemic MVPA was negatively associated with subsequent depressive symptoms (β = -0.147). Conversely, pre-pandemic depressive symptoms were positively associated with subsequent recreational screen time (β = 0.085), which in turn predicted heightened post-pandemic depressive symptoms (β = 0.076). When stratified by age, significant associations were found in adolescents but not children.ConclusionsSustained unhealthy changes in physical activity and recreational screen time were observed during the COVID-19 pandemic among children and adolescents. This study elucidates a potential reciprocal relationship between lifestyle behaviors and mental well-being. Effective interventions are emphasized to counter the negative impacts of insufficient physical activity and excessive screen use on the mental health of children and adolescents.

Perceptions of Falling Behind "Most White People": Within-Group Status Comparisons Predict Fewer Positive Emotions and Worse Health Over Time Among White (but Not Black) Americans.

Despite the persistence of anti-Black racism, White Americans report feeling worse off than Black Americans. We suggest that some White Americans may report low well-being despite high group-level status because of perceptions that they are falling behind their in-group. Using census-based quota sampling, we measured status comparisons and health among Black (N = 452, Wave 1) and White (N = 439, Wave 1) American adults over a period of 6 to 7 weeks. We found that Black and White Americans tended to make status comparisons within their own racial groups and that most Black participants felt better off than their racial group, whereas most White participants felt worse off than their racial group. Moreover, we found that White Americans' perceptions of falling behind "most White people" predicted fewer positive emotions at a subsequent time, which predicted worse sleep quality and depressive symptoms in the future. Subjective within-group status did not have the same consequences among Black participants.