Search Results (93)

In recent years, monoclonal antibodies targeting key cytokines underlying the occurrence of psoriatic skin lesions and joint involvement, i.e., Tumor Necrosis Factor-alpha (TNF-α), Interleukin 17 (IL-17), Interleukin 12 (IL-12), and Interleukin 23 (IL-23), have become more commonly used in the therapy of psoriasis. Due to the high effectiveness, a favorable safety profile, and growing availability of biological treatment methods, the number of patients receiving chronic monoclonal antibody therapy is increasing each year. However, the factors affecting the effectiveness of biological drugs are not fully recognized. The study aimed at analyzing the clinical profile of patients and non-specific inflammatory markers in terms of the response to the psoriasis treatment with IL-17, IL-23, IL-12/23, and TNF-α inhibitors. The analysis involved 185 patients receiving biological therapy in the Department of Dermatology and Venereology at the Medical University of Lodz, which resulted in a total of 222 treatment cycles (TC). The super-response was defined as 100% reduction in the Psoriasis Area and Severity Index (PASI 100), at week 16 (±4 weeks) of therapy. Our study indicates that the chance of achieving a super-response was higher among younger patients with no psoriatic lesions on palms and soles, not suffering from non-alcoholic fatty liver disease, previously treated with methotrexate, and characterized by a higher level of derived Neutrophil-to-Lymphocyte Ratio (dNLR) at the beginning of treatment. Full article

Introduction: Super responders (SRs)—patients achieving complete skin clearance (PASI = 0) soon after biologic initiation—represent a clinically relevant but underexplored phenotype. This study is one of the first real-world, multi-agent analyses comparing SR likelihood across biologic classes in plaque psoriasis. We assessed whether biologic choice predicts SR in routine clinical practice. Methods: We performed a retrospective, single-center study of 116 adults with moderate-to-severe plaque psoriasis initiating their first biologic (adalimumab, tildrakizumab, guselkumab, risankizumab, bimekizumab, or secukinumab). SR was defined as PASI = 0 at week 12. SR proportions (exact 95% CIs) were compared using Fisher’s exact tests and odds ratios (ORs). Multivariable logistic regression estimated adjusted associations between biologic and SR, controlling for age, sex, disease duration, BMI, baseline PASI, and prior cyclosporine/acitretin. Sensitivity analyses included Firth bias-reduced regression, the exclusion of sparse drug strata, and an alternative endpoint (PASI ≤ 1 at week 12). Results: Overall, 26/116 patients (22.4%) achieved SR. SR proportions differed by agent, highest with bimekizumab (11/17; 64.7%); Fisher’s p < 0.001 vs. others; OR = 12.83 (95% CI 4.17–39.50). In adjusted models, bimekizumab remained independently associated with SR (adjusted OR = 17.30; 95% CI 4.62–64.82; p = 2.35 × 10⁻⁵), while other covariates were not significant. Conclusions: In this real-world cohort, biologic selection—particularly bimekizumab—was the main determinant of early complete clearance. These findings highlight mechanistic class as a key driver of rapid, deep responses and support prospective validation with harmonized SR definitions and extended follow-up. Full article

Background/Objectives: Psoriasis is a chronic immune-mediated skin disease with an estimated global prevalence of 3%. Real-world studies have demonstrated that biologic therapies have transformed the management of moderate-to-severe psoriasis by providing optimal disease control and a favorable safety profile. However, a new challenge lies in identifying those most likely to achieve an early and sustained response, defined as ‘super-responders’ (SRs). This is particularly relevant given recent evidence suggesting that IL-23 inhibitors may have long-term disease-modifying effects by acting on tissue-resident memory T cells. Identifying positive and negative baseline predictors associated with achieving SR status in patients treated with anti-IL-23 agents. Methods: This retrospective observational study analyzed data from the electronic medical records of IRCCS Humanitas Research Hospital between June 2021 and June 2025. A total of 611 patients with moderate-to-severe psoriasis who were treated with risankizumab, guselkumab or tildrakizumab were included in the study. Clinical assessments were conducted at baseline and weeks 16, 28 and 52. SR status was defined as achieving a PASI score of ≤1 at week 16, with this score being maintained through weeks 28 and 52. Results: Of the 611 enrolled patients, 390 (63.8 %) achieved SR status. In multivariate logistic regression, disease duration ≤ 2 years was the strongest independent predictor (Odds Ratio [OR] 2.47, p = 0.025), followed by bio-naïve status (OR 1.53, p = 0.019). Obesity (OR 0.71, 95 % CI 0.45–1.13) and cardiometabolic comorbidities (OR 0.93, 95 % CI 0.63–1.38) were not significantly associated with response after adjustments. No serious adverse events or treatment discontinuations occurred during 52 weeks of follow-up. Conclusions: Shorter disease duration (≤2 years) and bio-naïve status were identified as independent predictors of SR status. Identifying these patients could inform the development of personalized treatment strategies, including dose optimization and extended dosing intervals. Full article

In the era of the “super-individual”, companion robots (or sex robots), as novel agents for intimate relationships, have provoked profound ethical controversies. This article responds to Fang Xudong’s defense of companion robots in terms of the “instrumentalization of womanhood” and further explores the possible stance of Confucian ethics towards companion robots. Companion robots risk fostering emotional self-deception, which violates the Confucian self-cultivation requirement of “sincerity within, manifesting outwardly” 诚于中，形于外. They also fail to fulfill the “generative virtue” 生生之德 encompassing biological reproduction and moral education through kinship and may even undermine the family’s function as a carrier of ethical practice. From a Confucian perspective, the “pseudo-intimacy” facilitated by companion robots might alleviate symptoms of social isolation in an atomized age, but it cannot replace the familial warmth characterized by “affection between father and son, distinct roles between husband and wife” 父子有亲，夫妇有别. Only in the ethical practice of facing the other and taking responsibility can one truly realize the ideal of “cultivating oneself and bringing all things to their ideal state” 成己成物. Full article

Aims: Individual weight loss results achieved with Glucagon-like Peptide-1 receptor agonists (GLP-1RA) vary significantly. Our aim was to describe the characteristics of patients with obesity who achieved ≥ 20% total weight loss (TWL) on liraglutide and appraise those findings through the prism of an evolving spectrum of GLP-1RA. Methods: This longitudinal prospective cohort study included 21 patients (90.5% females, age 50 (IQR 17) years, class II/III obesity (Body Mass Index ≥ 35 kg/m²) followed at the Edmonton Adult Bariatric Clinic for 65.1 (IQR 15.5) weeks. All patients received treatment with liraglutide 3.0 mg subcutaneously daily along with involvement in an integrated lifestyle modification program. Results: Liraglutide was well-tolerated, with its benefits experienced by >90% of patients. The vast majority were consistently tracking calories (95.2%, n = 20) and protein intake (90.5%, n = 19), achieving a calorie deficit of 651 (IQR 323) kcal/day, and had their mental health conditions and psychological issues successfully managed. At 16, 26, and 52 weeks, TWL was 14.3% (IQR 3.7), 18.7% (IQR 8.8), and 25.9% (IQR 9.6), respectively (p < 0.001). Over 20% TWL was achieved by 72.2% of patients by week 52. Conclusions: A select number of patients with obesity will attain weight loss that rivals bariatric surgery using liraglutide monotherapy. Despite liraglutide being less effective compared to newer agents on the market, some individuals will respond strongly and should be considered when other therapies are inaccessible. Given the societal burden and numerous challenges faced by people with obesity, GLP-1RA should be pursued in clinical practice to assist in achieving weight loss goals while being convenient and safe. Full article

American citizens are significantly more likely to experience property crime victimization than violent crime victimization. During a staffing crisis, police prioritize limited resources in combating serious crime; however, property crimes remain impactful to the community. Therefore, agencies need to consider innovative ways to control property crime, such as “super-cocooning” strategies that alert residents to recent offenses. These strategies intend to empower the community to implement guardianship and crime prevention measures. For these strategies to be effective, they require public buy-in and support. The present study implements a preregistered information provision survey experiment (N = 2412), similar to the strategy of super-cocooning, to assess whether the public is more likely to support such strategies to combat property crime. Although the sample held overall high support of this strategy, exposure to a super-cocooning door hanger prime produced no significant changes in perceived effectiveness. However, there was observed racial heterogeneity in the treatments: non-White respondents assigned to the treatment relative to White respondents experienced significantly increased support of super-cocooning strategies. Implications for light-footprint crime control strategies, particularly during a staffing crisis, are discussed. Full article

Identifying immunologic predictors of clinical responses remains an unmet need in the era of biologic therapy for psoriasis. Super responders (SRs), defined as patients achieving complete skin clearance within weeks of treatment initiation, represent an emerging clinical endotype; however, their immunological profiles remain insufficiently characterized. We conducted a prospective observational study to characterize serum cytokine profiles associated with SR status in biologic-naïve patients with moderate-to-severe plaque psoriasis treated with secukinumab, an IL-17A inhibitor. Twenty-eight patients were enrolled and stratified at week 12 into SR (PASI = 0; n = 9) and non-super responder (NSR; PASI > 0; n = 19) groups. Serum concentrations of 19 cytokines were analyzed at baseline and after 12 weeks of treatment. SRs displayed a distinct immunological signature characterized by significantly higher IL-13 and lower IL-18 baseline levels compared to NSRs (p = 0.002 and p = 0.007, respectively), alongside reduced baseline monocyte counts. L1-regularized logistic regression confirmed IL-13 and IL-18 as strong independent predictors of SR status (AUC = 0.91). Moreover, the IL-18/IL-13 ratio emerged as a highly discriminative biomarker (p = 0.00001, AUC = 0.86). Notably, SRs exhibited a more pronounced decline in IL-18 and IL-23 during treatment. Our findings provide novel insights into the immunopathogenesis of super response and suggest that an immunological milieu favoring Th2 polarization may promote superior outcomes with IL-17A blockade. Incorporating IL-13, IL-18, and their ratio into clinical algorithms may facilitate precision-guided biologic therapy in psoriasis. Full article

Event cameras respond to changes in log-brightness at the millisecond level, making them ideal for optical flow estimation. However, existing datasets from event cameras provide only low-frame-rate ground truth for optical flow, limiting the research potential of event-driven optical flow. To address this challenge, we introduce a low-latency event representation, unified voxel grid (UVG), and propose EVA-Flow, an EVent-based Anytime Flow estimation network to produce high-frame-rate event optical flow with only low-frame-rate optical flow ground truth for supervision. Furthermore, we propose rectified flow warp loss (RFWL) for the unsupervised assessment of intermediate optical flow. A comprehensive variety of experiments on MVSEC, DESC, and our EVA-FlowSet demonstrates that EVA-Flow achieves competitive performance, super-low-latency (5 ms), time-dense motion estimation (200 Hz), and strong generalization. Full article

Background: A shared definition of therapeutic targets in the treatment of atopic dermatitis (AD) allows for the identification of patients who respond rapidly (early responders [ERs]) and optimally (super responders [SRs]) to systemic treatments. A concomitant achievement of EASI75/≤7, PP-NRS ≤ 4, SCORAD-75/≤24, POEM ≤ 7, and DLQI ≤ 5 at 6 months of treatment has been defined as an ideal target for AD. Methods: Patients aged ≥ 12 years treated with dupilumab for moderate-to-severe AD in an Italian center for at least 2 years were analyzed. We defined ERs as those who achieved EASI ≤ 7, PP-NRS ≤ 4, POEM ≤ 7, and DLQI ≤ 5 within 32 weeks, and SRs and long responders (LRs) as those who maintained the target at 1 year and at 2 years, respectively. We subsequently compared baseline characteristics between those who fell within the above definitions and those who did not. Results: Of 171 patients with AD, 76.6% were ERs, 49.1% SRs, and 40.4% LRs. Achievement of combined outcomes was shown by 37.11% of patients at 16 weeks, and increased at the following time points by more than half of patients at 2 years of treatment. Except for a high baseline POEM that appears to be unfavorable for achieving early response (OR 0.93, CI 0.88–0.98, p = 0.006), no baseline characteristics were associated with ERs, SRs, or LRs in this population. Conclusions: According to our definition of responders, we were unable to identify a patient profile at baseline that predicts optimal therapeutic outcomes with dupilumab. Only baseline POEM seems to affect achievement of the selected outcomes. Dupilumab showed a rapid achievement of the outcomes with a stable response after 4 months of treatment, according our definitions. Shared definitions of the different categories of patient responders and a common therapeutic target are necessary for optimal management of AD. Full article

Background/Objectives: Cardiac resynchronization therapy (CRT) with fusion pacing (“LV only”), also known as fusion-CRT (f-CRT), represents a feasible alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BiVP), not only in cases of BiVP failure, but also as a primary therapy option due to its potential benefits over traditional CRT. Fusion pacing may be particularly beneficial in selected patients and understanding the structural and functional differences between responders could guide future optimization strategies. This study provides a descriptive comparison between super-responders (SRs) and non-super-responders (NSRs) undergoing fusion-CRT. Methods: Patients with RA/LV-only pacing systems or biventricular CRT systems operating predominantly in LV-only pacing mode due to intrinsic RV conduction were included. A follow-up protocol was conducted for all patients at 6 months and then annually. Data from the most recent follow-up were used for statistical analysis. Super-responders (SRs) were those with substantial reverse remodeling, quantified by a ≥30% reduction in LVESV and a stable LVEF of ≥45% at follow-up. Although SRs were defined based on these reverse remodeling criteria, separate analyses of additional echocardiographic parameters (e.g., left atrial dimensions) were performed to independently assess the broader impact of fusion-CRT on cardiac structure and function. Results: Among 71 patients, 55 were non-super-responders (NSRs) and 16 were super-responders (SRs), with a mean follow-up of 43.2 months. SRs were predominantly female and had smaller left ventricular (LV) dimensions: LVEDd (6.30 cm vs. 6.80 cm, p = 0.02), LVEDV (185 mL vs. 240 mL, p = 0.03), LVESV (132.5 mL vs. 175 mL, p = 0.03), and a higher LVEF (p = 0.03). The follow-up LVEF was positively correlated with changes in LVESV (ρ = 0.557, p < 0.001), but not with NYHA class changes (ρ = 0.184, p = 0.125). Larger baseline LV and left atrial (LA) volumes were associated with a reduced follow-up LVEF (LVESV: ρ = −0.426, p < 0.001; LVEDV: ρ = −0.394, p < 0.001; LAv: ρ = −0.374, p = 0.001). Both groups showed improvement in the NYHA class (p < 0.001, p = 0.007). MR improved significantly in SRs (p = 0.02) and worsened slightly in NSRs (p = 0.13), while TR worsened significantly in the NSRs group (p = 0.03). Conclusions: Our findings highlight key differences in clinical and echocardiographic parameters between SRs and NSRs following fusion-CRT. These observations may contribute to a better understanding of response patterns and inform future prospective studies aiming to optimize patient selection and timing of therapy. Full article

Introduction: Benralizumab has demonstrated rapid efficacy in treating severe eosinophilic asthma (SEA). This study aims to characterize early responses to benralizumab, the patient features observed in those with early responses, and the potential patient features that could predict them, and it also evaluates whether these improvements are sustained during a one-year follow-up (FUP) in clinical practice. Methods: This analysis was conducted using the ORBE II study database. ORBE II is an observational, retrospective study that included uncontrolled SEA adult patients treated with benralizumab according to routine clinical practice in Spain. We analysed patients with available data on the asthma control test (ACT) at baseline and within the first 120 days after benralizumab initiation, identifying ACT “Early Super-Responders” (ACT-ESR) as patients with a ≥9 point-improvement in the ACT score or reaching an absolute score of ≥24. Likewise, we assessed patients with available data on the pre-BD FEV₁ during the same study periods, defining those with a pre-BD FEV₁ increment of ≥230 mL as FEV₁-ESR patients. Clinical outcomes were described up to 1 year of FUP. Results: A total of 45 and 65 patients with data for ACT and FEV₁, respectively, during the first 120 days of treatment were analysed. Of those, 55.5% and 58.5% of patients were categorized as ACT-ESR and FEV₁-ESR, respectively. At baseline, both groups showed high T2 inflammation markers and a high prevalence of comorbidities (chronic rhinosinusitis with nasal polyposis: 56% and 50%; gastro-oesophageal reflux disease: 24% and 40%, respectively). Poor asthma control (ACT < 20) was observed at baseline in 96% of ACT-ESR, while impaired lung function (pre-BD FEV₁ < 80%) was present in 71.7% of FEV₁-ESR. Oral corticosteroid (OCS) dependency affected 25% and 30% of ACT-ESR and FEV₁-ESR, respectively. The early gains observed in ACT-ESR and FEV₁-ESR were sustained up to 1 year of FUP, with 90.5% and 66.7% of patients achieving a super-response (zero exacerbations and no OCS use) and 92.0% and 71.1% meeting clinical remission criteria (zero exacerbations, no OCS use, ACT ≥ 20 and pre-BD FEV₁ increment of ≥100 mL), respectively. Conclusions: Benralizumab provides early benefits for SEA patients in clinical practice, with more than half achieving early super-responses in both ACT score and lung function. These improvements were sustained over a 1-year FUP, resulting in high rates of clinical remission. Full article

Electrical and mechanical dyssynchrony (MD) underlies left ventricular (LV) contractile dysfunction in patients with heart failure (HF) and left bundle branch block (LBBB). In some cases, cardiac resynchronization therapy (CRT) almost completely reverses LV contractile dysfunction. The LBBB electrocardiographic Strauss criteria and MD assessment were proposed to improve CRT response. However, using these techniques separately does not improve LV contraction in 20–40% of patients after CRT device implantation. We aimed to evaluate whether the combined use of electrocardiography (ECG), speckle-tracking echocardiography (STE) and cardiac scintigraphy could improve the prognosis of CRT super-response in patients with HF and Strauss LBBB criteria during a 6-month follow-up period. The study prospectively included patients with HF, classified as New York Heart Association (NYHA) functional class (FC) II–III in sinus rhythm with Strauss LBBB criteria and reduced left ventricular ejection fraction (LVEF). Before and 6 months after CRT device implantation, ECG, STE and cardiac scintigraphy were performed. The study’s primary endpoint was the NYHA class improvement ≥ 1 and left ventricle end systolic volume decrease > 30% or LVEF improvement > 15% after 6 months of CRT. Based on collected data, we developed a prognostic model regarding the CRT super-response. Out of 54 (100.0%) patients, 39 (72.2%) had a CRT super-response. Patients with CRT super-response were likelier to have a greater S wave amplitude in V₂ lead (p = 0.004), higher rates of global longitudinal strain (GLS) (p = 0.001) and interventricular delay (IVD) (p = 0.005). Only three indicators (S wave amplitude in V₂ lead, GLS and IVD) were independently associated with CRT super-response in univariable and multivariable logistic regression. We created a prognostic model based on the logistic equation and calculated a cut-off value (>0.73). The resulting ROC curve revealed a discriminative ability with an AUC of 0.957 (sensitivity 87.2%; specificity 100.0%). The electrical and mechanical dyssynchrony assessment using ECG, STE and cardiac scintigraphy is useful in the prediction of CRT super-response in patients with HF and Strauss LBBB criteria during a 6-month follow-up period. Our prognostic model can identify patients who are super-responders to CRT. Full article

Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (PRLT) with Lutetium-177 ([¹⁷⁷Lu]Lu-PSMA) is a safe and effective treatment for metastatic castration-resistant prostate cancer (mCRPC). The aim of our study was to evaluate clinical variables of patients with extreme response to PRLT and to assess its immunomodulatory potential. Methods: This retrospective study included 36 patients from two centers achieving extreme response after [¹⁷⁷Lu]Lu-PSMA PRLT. The primary outcomes were the duration of maintained response in months (MR) and improvement post-therapy—clinically, serologically, and on molecular (PET/CT) imaging. We examined several variables, including pathology, gene sequencing, baseline PSA, Gleason score, prior therapies, number of PRLT cycles, and pattern of disease, to identify potential factors that may influence the extreme response. Results: Between 2018 and mid-September 2024, 36 men with mCRPC received a mean of three cycles of [¹⁷⁷Lu]Lu-PSMA PRLT. Patients were subgrouped according to clinical variables versus MR. A total of 17 patients had ≥12 months MR (17/36, 47%). The longest duration of MR was 99 months and a mean of 17.44 months (95% CI 10.05–24.84). Previous lines of treatment were evaluated for MR, p = 0.172. Pattern of disease (bone, lymph node, liver, and peritoneal) was evaluated for MR, p = 0.721. The Gleason score was evaluated for MR, p = 0.871. Patients with known BRCA sequencing status (n = 12) were analyzed with mean MR: BRCA1/2 wild-type, 6/12 (50%), 6.67 months; BRCA 1/2 negative, 1/12 (8.33%), 7 months; BRCA germline negative and somatic positive, 1/12 (8.33%), 36 months; BRCA germline negative, somatic negative, 2/12 (16.67%), 27 months; and BRCA 2 positive, 2/12 (16.67%), 43 months. Conclusions: We propose there may be intrinsic mechanisms suggesting the immunomodulatory enhancement of ionizing radiation, primarily driving extreme responses. Full article

The growing body of research on children’s understanding of extraordinary minds has demonstrated that children believe in the persistence of mental functioning after death. However, beyond the continuity of mind, the supernatural conception of death often involves the concept of the disembodied mind, which transcends the constraints of the physical body, possessing supernatural mental capacities. The current study investigated whether children differentiate between a dead agent’s mind and ordinary minds in terms of their perceptual and information-updating capacities. In a location-change false-belief task, which involved a story of a mouse protagonist that was either eaten by an alligator or not, 4- to 6-year-old Korean children (N = 114) were asked about the mental states of the protagonist, an ordinary adult (mom), and God. The results showed (1) older children’s tendency to respond in a way that differentiated (the living) mom from the dead protagonist, (2) an increasing trend of differentiating God’s super-knowingness from ordinary minds with age, and (3) inconclusive evidence regarding children’s differential responses to the dead versus living protagonist. This study suggests that children are not predisposed to view dead agents as possessing a disembodied and supernatural mind, highlighting the importance of cultural learning in the development of such religious concepts. Full article

The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D), binds to the vitamin D receptor (VDR) with high affinity. The VDR then heterodimerizes with the retinoid X receptor (RXR) and associates with vitamin D response elements (VDREs) to regulate the transcription of target genes. Bexarotene (Bex) is an RXR ligand (rexinoid) developed to treat cutaneous T-cell lymphoma and is a putative therapeutic for other diseases. We postulate that VDR ligands (1,25D) and RXR ligands (Bex/analogs) can “synergize” to “super-activate” the VDR-RXR heterodimer. This “cross-talk” could allow disorders treated with high-dose Bex therapy (leading to significant adverse side effects) to instead be treated using both low-dose Bex and vitamin D. Thus, we designed experiments to examine the effect of both VDR and RXR ligands, alone and in combination, to activate VDR-RXR-mediated transcription. The goal was to determine if selected RXR-specific ligands can synergize with vitamin D to amplify RXR-VDR activity. The results demonstrate a synergistic effect with both Bex and 1,25D which could be further modulated by (1) the protein levels (or polymorphic version) of VDR present in the cell, (2) the concentration of the ligands, (3) the cellular “background” (e.g., brain cells versus kidney cells), (4) the nature of the VDRE platform, or (5) the type of rexinoid (Bex analogs). Our findings suggest that diseases that respond to treatment with either vitamin D, or with rexinoids, may be amenable to enhanced therapeutic potential by employing multi-ligand dosing via combinatorial therapy. Full article