Real Sets Research Articles

Tobacco Smoking or Nicotine Phenotype and Severity of Clinical Presentation at the Emergency Department (SMOPHED): Protocol for a Noninterventional Observational Study.

In the last few years, several nicotine products have become available as alternatives to smoking tobacco. While laboratory and limited clinical studies suggest that these devices are less toxic compared to classic tobacco cigarettes, very little is known about their epidemiological impact. Visiting the emergency department (ED) often represents the first or even the only contact of patients with the health care system. Therefore, a study conducted at the ED to assess the impact of these products on health can be reliable and reflect a real-life setting. The aim of this noninterventional observational study (SMOPHED study) is to analyze the association between the severity of clinical presentation observed during ED visits among patients using various nicotine products and the subsequent outcomes, specifically hospitalization and mortality. Outcomes (hospitalization and mortality in the ED) will be examined in relation to various patterns of nicotine products use. We plan to enroll approximately 2000 participants during triage at the ED. These individuals will be characterized based on their patterns of tobacco and nicotine consumption, identified through a specific questionnaire. This categorization will allow for a detailed analysis of how different usage patterns of nicotine products correlate with the clinical diagnosis made during the ED visits and the consequent outcomes. Enrollment into the study started in March 2024. We enrolled a total of 901 participants in 1 month (approximately 300 potential participants did not provide the informed consent to participate). The data will be analyzed by a statistician as soon as the database is completed. Full data will be published by December 2024. There is substantial debate about the harm reduction potential of alternative nicotine products in terms of their smoking-cessation and risk-reduction potential. This study represents an opportunity to document epidemiological data on the link between the use of different types of nicotine products and disease diagnosis and severity during an ED visit, and thus evaluate the harm reduction potential claims for these products. PRR1-10.2196/54041.

Adherence, persistence and treatment switching in psoriasis.

Aim: This study aims to investigate drug utilization patterns in the treatment of psoriasis (PsO) from 1 to 5years in a real-life setting with Adalimumab (Ada), Etanercept (Eta), Ustekinumab (Ust), Golimumab (Gol), Ixekizumab (Ixe), Secukinumab (Sec) and Apremilast (Apr). Materials & methods: Data from an observational study were used to calculate adherence using the Proportion of Days Covered (PDC) method and persistence. Results & conclusion: Treatment adherence was found to be good for all the drugs studied across all years of analysis, while persistence was suboptimal, showing a marked decrease from the third year of study onward. In the treatment of PsO, greater attention needs to be paid to treatment persistence.

The Effect of Clothes on Blood Pressure Measurement in Normotensive and Hypertensive Subjects in a Real-Life Setting.

The effect of clothing on the recording of blood pressure in a normotensive and hypertensive population remains essential to diagnosing and managing. This is a cross-sectional study to measure blood pressure using a validated oscillometric sphygmomanometer in two populations. The records were made over the thicker sleeve arm and non-sleeved arm (either on bare arm or indicating the removal of the outermost garment). Clothing was categorized according to how patients attended the outpatient clinic based on the real world. A total of 75 patients were included with a diagnosis of hypertension whose mean age was 67.1 years (SD ± 16.3). The group of normotension included 63 patients whose mean age was 21.1 years (SD ± 2.2). There was not variability related to technique or inherent to the condition of the subject on the first and second measurements of blood pressure. In the comparative analysis, the group with normotension did not report a significant difference in systolic or diastolic blood pressure due to the effect of clothing during the first or second measurement (p > 0.05). In the group with hypertension, a significant difference was observed in the first measurement, between the group over-the-sleeve and non-sleeved arm (systolic blood pressure, p: 0.021 and diastolic, p: 0.001). However, when the variable order of measurement was analyzed by randomizing the initial registry with or without clothing was not found a statistical difference. Clothing does not a significant difference in the measure of blood pressure in a normotensive or hypertensive population.

Small countries facing the technological revolution: fostering synergies between economic complexity and foresight research

Purpose Although the significance of technological progress in economic development is well-established in theory and policy, it has remained challenging to agree upon shared priorities for strategies and policies. This paper aims to develop a model of how policymakers can develop effective and easy to communicate strategies for science, technology and economic development. Design/methodology/approach By integrating insights from economic complexity, competitiveness and foresight literature, a replicable research framework for analysing the opportunities and challenges of technological revolutions for small catching-up countries is developed. The authors highlight key lessons from piloting this framework for informing the strategy and policies for bioeconomy in Estonia towards 2030–2050. Findings The integration of economic complexity research with traditional foresight methods establishes a solid analytical basis for a data-driven analysis of the opportunities for industrial upgrading. The increase in the importance of regional alliances in the global economy calls for further advancement of the analytical toolbox. Integration of complexity, global value chains and export potential assessment approaches offers valuable direction for further research, as it enables discussion of the opportunities of moving towards more knowledge-intensive economic activities along with the opportunities for winning international market share. Originality/value The research merges insights from the economic complexity, competitiveness and foresight literature in a novel way and illustrates the applicability and priority-setting in a real-life setting.

Single-Center Experience of Using Liraglutide in Adolescents With Obesity +/- Type 2 Diabetes.

Background Childhood obesity is recognized as a chronic illness with limited therapeutic options. Tackling obesity (BMI; the weight in kilograms divided by the square of the height in meters, at the 95th percentile or higher) with lifestyle interventions, especially in adolescents, has proven to be a daunting task, yielding only modest results. Research on the use of liraglutide for weight reduction in pediatric patients has yielded conflicting results. Notably, there is a lack of studies in the Middle East reporting on the outcomes of glucagon-like peptide 1 (GLP-1)receptor agonists in treating obesity in children and adolescents, with or without diabetes. This study, conducted in the Middle East, represents the first investigation into the utilization of liraglutide for weight reduction in this pediatric population. Methods This retrospective study collected data on 22 consecutive participants, aged 12 to 19 years, who were diagnosed with obesity (defined as having a BMI greater than the 95th percentile for their age and sex) and had either type 2 diabetes mellitus(T2DM)or were non-diabetic who attended endocrine clinics in Sidra Medicine, Doha, Qatar, between 2020 and 2022. The study protocol involved a liraglutide treatment period spanning 18 months (72 weeks), with scheduled follow-up appointments at six-month intervals. The primary endpoints were changes in weight and BMI from baseline to the 72-week mark. Secondary endpoints were safety measures and changes in HbA1c. Results Out of the initial cohort of 22 patients, 12 completed the full 72-weekduration of the study, while 10 patients either discontinued treatment or did not adhere to the prescribed medication regimen due to side effects. Among the 12 patients who completed the study, six had a diagnosis of T2DM. At baseline, the weight, standard deviation score (SDS), BMI, and BMI standard deviation (SD) were 113.9 kg, 2.9, 40.9 kg/m2, and 2.6 respectively. At the 18-month follow-up, the weight, SDS, BMI, and BMI SD were 117.8kg,2.6, 39kg/m2, and 2.5, respectively. Thus, no statistically significant change in the weight parameters was evident at 18 months compared to baseline. Dropout from the study and poor compliance were high (10 out of 22 patients) due to side effects, mainly gastrointestinal (nausea, abdominal pain, diarrhea, and vomiting). No statistically significant differences were observed between obese vs. obese with T2DM. No significant change in HbA1c was found between baseline and treatment follow-up in the diabetes patients. No adverse effects in terms of impairment of liver and kidney function or pancreatitis were observed. Conclusions The administration of liraglutide to adolescents with obesity, regardless of whether they had T2DMor not, in a real-life setting, did not yield statistically significant reductions in BMI/weight parameters, and HbA1c levels at the 72-week mark. Nevertheless, the study findings indicate that liraglutide is deemed safe for utilization within this age group, despite the presence of mild gastrointestinal side effects.

Reconsidering stepped wedge cluster randomized trial designs with implementation periods: Fewer sequences or the parallel-group design with baseline and implementation periods are potentially more efficient.

When designing a cluster randomized trial, advantages and disadvantages of tentative designs must be weighed. The stepped wedge design is popular for multiple reasons, including its potential to increase power via improved efficiency relative to a parallel-group design. In many realistic settings, it will take time for clusters to fully implement the intervention. When designing the HEALing (Helping to End Addiction Long-termSM) Communities Study, implementation time was a major consideration, and we examined the efficiency and practicality of three designs. Specifically, a three-sequence stepped wedge design with implementation periods, a corresponding two-sequence modified design that is created by removing the middle sequence, and a parallel-group design with baseline and implementation periods. In this article, we study the relative efficiencies of these specific designs. More generally, we study the relative efficiencies of modified designs when the stepped wedge design with implementation periods has three or more sequences. We also consider different correlation structures. We compare efficiencies of stepped wedge designs with implementation periods consisting of three to nine sequences with a variety of corresponding designs. The three-sequence design is compared to the two-sequence modified design and to the parallel-group design with baseline and implementation periods analysed via analysis of covariance. Stepped wedge designs with implementation periods consisting of four or more sequences are compared to modified designs that remove all or a subset of 'middle' sequences. Efficiencies are based on the use of linear mixed effects models. In the studied settings, the modified design is more efficient than the three-sequence stepped wedge design with implementation periods. The parallel-group design with baseline and implementation periods with analysis of covariance-based analysis is often more efficient than the three-sequence design. With respect to stepped wedge designs with implementation periods that are comprised of more sequences, there are often corresponding modified designs that improve efficiency. However, use of only the first and last sequences has the potential to be either relatively efficient or inefficient. Relative efficiency is impacted by the strength of the statistical correlation among outcomes from the same cluster; for example, the relative efficiencies of modified designs tend to be greater for smaller cluster auto-correlation values. If a three-sequence stepped wedge design with implementation periods is being considered for a future cluster randomized trial, then a corresponding modified design using only the first and last sequences should be considered if sole focus is on efficiency. However, a parallel-group design with baseline and implementation periods and analysis of covariance-based analysis can be a practical, efficient alternative. For stepped wedge designs with implementation periods and a larger number of sequences, modified versions that remove 'middle' sequences should be considered. Due to the potential sensitivity of design efficiencies, statistical correlation should be carefully considered.

Motor band sign is specific for amyotrophic lateral sclerosis and corresponds to motor symptoms.

Magnetic resonance imaging can detect neurodegenerative iron accumulation in the motor cortex, called the motor band sign. This study aims to evaluate its sensitivity/specificity and correlations to symptomatology, biomarkers, and clinical outcome in amyotrophic lateral sclerosis. This prospective study consecutively enrolled 114 persons with amyotrophic lateral sclerosis and 79 mimics referred to Karolinska University Hospital, and also 31 healthy controls. All underwent 3-Tesla brain susceptibility-weighted imaging. Three raters independently assessed motor cortex susceptibility with total and regional motor band scores. Survival was evaluated at a median of 34.2 months after the imaging. The motor band sign identified amyotrophic lateral sclerosis with a sensitivity of 59.6% and a specificity of 91.1% versus mimics and 96.8% versus controls. Higher motor band scores were more common with genetic risk factors (p = 0.032), especially with C9orf72 mutation, and were associated with higher neurofilament light levels (std. β 0.22, p = 0.019). Regional scores correlated strongly with focal symptoms (medial region vs. gross motor dysfunction, std. β -0.64, p = 0.001; intermediate region vs. fine motor dysfunction, std. β -0.51, p = 0.031; lateral region vs. bulbar symptoms std. β -0.71, p < 0.001). There were no associations with cognition, progression rate, or survival. In a real-life clinical setting, the motor band sign has high specificity but relatively low sensitivity for identifying amyotrophic lateral sclerosis. Associations with genetic risk factors, neurofilament levels and somatotopic correspondence to focal motor weakness suggest that the motor band sign could be a suitable biomarker for diagnostics and clinical trials in amyotrophic lateral sclerosis.

Effectiveness and safety profile of mepolizumab in chronic rhinosinusitis with nasal polyps: Real life data in a tertiary care

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a type 2 pattern of inflammation. Mepolizumab was approved for the treatment of CRSwNP in 2021, it may be useful to evaluate its safety profile in a real-world setting. AimThis work aimed to prospectively highlight the effectiveness and safety profile of Mepolizumab in patients with CRSwNP enrolled in the Otorhinolaryngology Unit of the University Hospital of Messina. MethodsAn observational cohort study was carried out considering all patients treated with Mepolizumab. A descriptive analysis was conducted reporting all demographic characteristics, endoscopic evaluations, and symptom conditions. ResultsA total of 30 patients were treated with Mepolizumab, one patient discontinued the treatment. A statistically significant reduction in the Sino-Nasal Outcome Tests-22 (SNOT-22) and nasal polyp score (NPS) was shown at the 6th and 12th months compared to baseline values (SNOT-22, −33 and − 43, p < 0.001 for both comparisons; NPS, 0 and − 1, p < 0.001 for both comparisons). The median (Q1–Q3) sniffin' sticks test score increased from 7 (6–8) at the 6th month to 11 (10−13) at the 12th month. Seven patients (24.1 %) reported pain at the injection site, accompanied by redness, warmth, and tenderness within the first 24 h post-injection with a median duration of three days from the onset. ConclusionsGiven the optimal treatment response and the minimal adverse effects observed, clinicians should consider Mepolizumab a safe and effective treatment in CRSwNP patients. Further studies in real-life setting are necessary to better understand the long-term effects.

Small kinetic mixing in string theory

Kinetic mixing between gauge fields of different U(1) factors is a well-studied phenomenon in 4d EFT. In string compactifications with U(1)s from sequestered D-brane sectors, kinetic mixing becomes a key target for the UV prediction of a phenomenologically important EFT operator. Surprisingly, in many cases kinetic mixing is absent due to a non-trivial cancellation. In particular, D3-D3 kinetic mixing in type-IIB vanishes while D3-anti-D3 mixing does not. This follows both from exact CFT calculations on tori as well as from a leading-order 10d supergravity analysis, where the key cancellation is between the C2 and B2 contribution. We take the latter approach, which is the only one available in realistic Calabi-Yau settings, to a higher level of precision by including sub-leading terms of the brane action and allowing for non-vanishing C0. The exact cancellation persists, which we argue to be the result of \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{SL}}\\left(2,{\\mathbb{R}}\\right)$$\\end{document} self-duality. We note that a B2C2 term on the D3-brane, which is often missing in the recent literature, is essential to obtain the correct zero result. Finally, allowing for \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{SL}}\\left(2,{\\mathbb{R}}\\right)$$\\end{document}-breaking fluxes, kinetic mixing between D3-branes arises at a volume-suppressed level. We provide basic explicit formulae, both for kinetic as well as magnetic mixing, leaving the study of phenomenologically relevant, more complex situations for the future. We also note that describing our result in 4d supergravity appears to require higher-derivative terms — an issue which deserves further study.

Endocrine disruptors, aryl hydrocarbon receptor and cortisol secretion.

Endocrine disruptors exert a plethora of effects in endocrine tissues, from altered function to carcinogenesis. Given its lipophilic nature, the adrenal cortex represents an ideal target for endocrine disruptors and thus, possibly, xenobiotic-induced adrenocortical dysfunction. However, there is no clear understanding of the effect of endocrine disruptors on adrenal steroidogenesis, in particular as regards the aryl hydrocarbon receptor (AHR) pathway, one of the key mediators. The present review recapitulates available evidence on the effects of AHR ligands on adrenal steroidogenesis, with focus on cortisol secretion. Short-term exposure to AHR ligands most often induced a stress-like corticosteroid response followed by decreased responsiveness to stressors with long-term exposure. This was observed in several experimental models across species as well as in animals and humans in real-life settings. Prenatal exposure led to different effects according to sex of the offspring, as observed in murine models and in children from mothers in several countries. In vitro findings proved highly dependent on the experimental setting, with reduced cortisol response and steroidogenic enzyme synthesis mostly observed in fish and increased cortisol synthesis and secretion observed in murine and human adrenal cell lines. Of note, no AHR-binding element was detected in steroidogenic enzyme promoters, suggesting the involvement of additional factors. Ourreview provides evidence for the impact of AHR ligands on adrenocortical function and indicates further avenues of research to better clarify its effects.

The Possible Synergistic Pharmacological Effect of an Oral Berberine (BBR) and Curcumin (CUR) Complementary Therapy Alleviates Symptoms of Irritable Bowel Syndrome (IBS): Results from a Real-Life, Routine Clinical Practice Settings-Based Study.

Irritable bowel syndrome (IBS) is a prevalent chronic functional gastrointestinal disorder, characterised by recurrent abdominal discomfort and altered bowel movements. IBS cause a significantly negative impact on quality of life (QoL). Growing pharmacological evidence suggests that berberine (BBR) and curcumin (CUR) may mitigate IBS symptoms through multiple complementary synergistic mechanisms, resulting in the attenuation of intestinal inflammation and regulation of bowel motility and gut functions. In the present observational study conducted under real-life routine clinical practice settings, 146 patients diagnosed with IBS were enrolled by general practitioner clinics and pharmacies in Belgium. For the first time, this study assessed the potential synergistic pharmacological effect of a combined oral BBR/CUR supplement (Enterofytol® PLUS, containing 200 mg BBR and 49 mg CUR) (two tablets daily for 2 months), serving as complementary therapy in the management of IBS. Following the 2-month supplementation, significant improvements were observed in the patients' IBS severity index (IBSSI) (47.5%) and all the primary IBS symptoms, such as abdominal discomfort (47.2%), distension (48.0%), intestinal transit (46.8%), and QoL (48.1%) (all p < 0.0001). The improvement in the patients' IBSSI was independent of age, sex, and IBS sub-types. The patients' weekly maximum stool passage frequency decreased significantly (p < 0.0001), and the stool status normalized (p < 0.0001). The patients' need for concomitant conventional IBS treatment decreased notably: antispasmodics by 64.0% and antidiarrhoeals by 64.6%. Minor adverse effects were reported by a small proportion (7.1%) of patients, mostly gastrointestinal. The majority (93.1%) experienced symptom improvement or resolution, with a high satisfaction rate (82.6%) and willingness to continue the supplementation (79.0%). These findings support the potential synergistic pharmacological role of BBR and CUR in IBS, and their co-supplementation may alleviate IBS symptoms and improve QoL.

Event detection in football: Improving the reliability of match analysis.

With recent technological advancements, quantitative analysis has become an increasingly important area within professional sports. However, the manual process of collecting data on relevant match events like passes, goals and tacklings comes with considerable costs and limited consistency across providers, affecting both research and practice. In football, while automatic detection of events from positional data of the players and the ball could alleviate these issues, it is not entirely clear what accuracy current state-of-the-art methods realistically achieve because there is a lack of high-quality validations on realistic and diverse data sets. This paper adds context to existing research by validating a two-step rule-based pass and shot detection algorithm on four different data sets using a comprehensive validation routine that accounts for the temporal, hierarchical and imbalanced nature of the task. Our evaluation shows that pass and shot detection performance is highly dependent on the specifics of the data set. In accordance with previous studies, we achieve F-scores of up to 0.92 for passes, but only when there is an inherent dependency between event and positional data. We find a significantly lower accuracy with F-scores of 0.71 for passes and 0.65 for shots if event and positional data are independent. This result, together with a critical evaluation of existing methodologies, suggests that the accuracy of current football event detection algorithms operating on positional data is currently overestimated. Further analysis reveals that the temporal extraction of passes and shots from positional data poses the main challenge for rule-based approaches. Our results further indicate that the classification of plays into shots and passes is a relatively straightforward task, achieving F-scores between 0.83 to 0.91 ro rule-based classifiers and up to 0.95 for machine learning classifiers. We show that there exist simple classifiers that accurately differentiate shots from passes in different data sets using a low number of human-understandable rules. Operating on basic spatial features, our classifiers provide a simple, objective event definition that can be used as a foundation for more reliable event-based match analysis.

Social Media Influence on Emerging Adults’ Prosocial Behavior: A Systematic Review

Current literature has provided substantial empirical evidence on how different types of factors influence prosocial behavior, but limited literature explores the relationship between online social media factors and their psychological influence on emerging adults’ prosocial behavior. Moreover, the majority of experimental investigations have utilized self-reported questionnaires or irrelevant economic games to reflect people’s prosocial behavior instead of measuring prosocial behavior demonstrated in real-life, natural settings. Considering the gaps in past research, this systematic review aims to identify literature regarding the influence of social media on emerging adults’ prosocial behaviors. The review focuses on studies that observed individuals’ prosocial behavior in real-life settings to eliminate social desirability bias and accurately establish the effects of social media on emerging adults’ prosocial behavior.

Post-Transplant Cyclophosphamide versus Anti-Thymocyte Globulin in Patients with Hematological Malignancies Treated with Allogeneic Hematopoietic Stem Cell Transplantation from Haploidentical and Matched Unrelated Donors: A Real-Life Experience.

Background: Post-transplant cyclophosphamide (PTCY) is widely used as graft versus host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplant (HSCT) recipients, with reported clinical benefits in patients who underwent transplant from a matched unrelated donor (MUD). However, real-life data on clinical efficacy and safety of PTCY in haploidentical and MUD transplantations are still poor. Methods: In our real-life retrospective observational study, we included a total of 40 consecutive adult patients who underwent haploidentical or MUD HSCT for various hematological malignancies and who received PTCY (n = 24) or ATG (n = 16) as GvHD prophylaxis at Hematology Units from hospitals of Salerno and Avellino, Italy, and clinical outcomes were compared. Results: We showed protective effects of PTCY against disease relapse with the relapse rate after transplantation of 16% versus 50% in the ATG arm (p = 0.02). All-cause mortality was lower (36% vs. 75%; p = 0.02) and the 2-year overall survival was slightly superior in patients administered PTCY (61% vs. 42%; p = 0.26). Conclusions: We support the use of PTCY, even in a real-life setting; however, the optimization of this protocol should be further investigated to better balance relapse prevention and GvHD prophylaxis.

Rapid and sustained resolution in generalized pustular psoriasis with IL-17A inhibitors required high adherence: a 96-week analysis in a real-life setting.

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening skin disease often requiring long-term therapy. We aimed to evaluate the use of Interleukin (IL)-17A inhibitors (secukinumab and ixekizumab) in GPP patients over 96 weeks. We retrospectively analyzed a case series of 18 patients with GPP who received secukinumab (n = 13) and ixekizumab (n = 5) therapy with a 96-week follow-up period. The primary effectiveness analysis included determining the percentage of patients who achieved ≥90% or 100% improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score. Adherence was captured using the medication possession ratio (MPR). Using the as-observed (AO) method, 87% and 67% of patients treated with secukinumab or ixekizumab achieved GPPASI 90and 100responses, respectively. At Week 96, the mean GPPASI improvements from baseline GPPASI were 96.3% (95% CI: 0.91-1.01) using the AO method. After Week 48, 14 patients tapered (n = 8) or terminated (n = 6) the treatment. High-adherence therapy (MPR ≥ 80%) was significantly superior to the low-adherence group in the rate of patients achieving a GPPASI 100 response (AO, 100% vs. 38%, P < 0.05). By Week 96, 5 (27.8%) patients had new GPP flares, and 4 (80%) were in the low-adherence group. No new safety signals occurred. IL-17A inhibitors led to effective and sustained improvement in GPP patients, and high-adherence therapy had long-term positive effects on skin clearance. Given its relapsing nature, improving compliance is beneficial for long-term clinical management.

Risk of Cardiovascular Events in People with HIV (PWH) Treated with Integrase Strand-Transfer Inhibitors: The Debate Is Not Over; Results of the SCOLTA Study.

Cardiovascular disease (CVD) is common in people with HIV (PWH), and has great impact in terms of morbidity and mortality. Several intertwined mechanisms are believed to play a role in determining the increased risk of CVD, including the effect of certain antiretrovirals; among these, the role of integrase strand-transfer inhibitors (INSTIs) is yet to be fully elucidated. We conducted a multicenter, observational study comprising 4984 PWH evaluating the antiretroviral therapy (ART)-related nature of CVD in real life settings, both in naïve vs. treatment-experienced people. A comparison was conducted between INSTIs vs. either protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) considering demographic, baseline clinical characteristics, incidence of CVD in both 2-year and complete follow-up periods. Among 2357 PWH exposed to INSTIs, 24 people experienced CVD; the corresponding figure was 12 cases out of 2599 PWH exposed to other ART classes. At univariate and multivariate analysis, a tendency towards an increased risk of CVD was observed in the 2-year follow-up period in PWH exposed to INSTIs in the absence, however, of statistical significance. These findings leave open the hypothesis that INSTIs may play a role, albeit minimal, in determining an increased risk of CVD in PWH.

Differentiable simulation of a liquid argon time projection chamber

Liquid argon time projection chambers (LArTPCs) are widely used in particle detection for their tracking and calorimetric capabilities. The particle physics community actively builds and improves high-quality simulators for such detectors in order to develop physics analyses in a realistic setting. The ability of these simulators to mimic real, measured data is limited by the modeling of the physical detectors used for data collection. This modeling can be improved by performing dedicated calibration measurements. Conventional approaches calibrate individual detector parameters or processes one at a time. However, the impact of detector processes is entangled, making this a poor description of the underlying physics. We introduce a differentiable simulator that enables a gradient-based optimization, allowing for the first time a simultaneous calibration of all detector parameters. We describe the procedure of making a differentiable simulator, highlighting the challenges of retaining the physics quality of the standard, non-differentiable version while providing meaningful gradient information. We further discuss the advantages and drawbacks of using our differentiable simulator for calibration. Finally, we provide a starting point for extensions to our approach, including applications of the differentiable simulator to physics analysis pipelines.

The steroid-sparing effect of JAK inhibitors across multiple patient populations.

JAK-inhibitors (JAK-i) represent an effective treatment in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA). Oral glucocorticoids (OGC) are commonly used in combination with JAK-i to reach therapeutic target. We aimed to assess, in a real-life setting, the reduction of OGC dose during JAK-i treatment in active RA and PsA patients. We prospectively enrolled 103 patients (88 RA, 15 PsA) treated with JAK-i: 24% bio-naïve (b-naïve), 76% bDMARD-insufficient responders (bDMARD-IR) and 40% difficult to treat (D2T), defined as failure of ≥2 bDMARDs with different mechanism of action. Disease activity (DAS28 and DAPSA, VAS-pain, GH) and OGC dose was collected at baseline and after 3, 6 and 12 months (T3, T6, T12) of treatment. In all the cohort and in b-naïve patients we reported a reduction of OGC dose at all time-points; bDMARD-IR patients were able to reduce OGC dose at T3 and T12; D2T ones only at T3. We reported an improvement of disease activity and withdrawal of OGC as early as three months of therapy, at all time-points, regardless of line of bDMARD treatment. Chronic OGC may cause detrimental bone, metabolic, cardiovascular side effects and infections; therefore JAK-i steroid-sparing effect may be beneficial for patients in long-term treatment.

DeFTA: A plug-and-play peer-to-peer decentralized federated learning framework

Federated learning (FL) is a pivotal catalyst for enabling large-scale privacy-preserving distributed machine learning (ML). By eliminating the need for local raw dataset sharing, FL substantially reduces privacy concerns and alleviates the isolated data problem. However, in reality, the success of FL is predominantly attributed to a centralized framework called FedAvg [1], in which workers are responsible for model training, and servers are in control of model aggregation. Nevertheless, FedAvg's centralized worker-server architecture has raised new concerns, including low scalability of the cluster, risk of data leakage, and central server failure or even defection. To overcome these challenges, we propose Decentralized Federated Trusted Averaging (DeFTA), a decentralized FL framework that serves as a plug-and-play replacement for FedAvg, bringing instant improvements to security, scalability, and fault-tolerance in the federated learning process. In essence, it primarily consists of a novel model aggregating formula with theoretical performance analysis, and a decentralized trust system (DTS) to significantly enhance system robustness. Extensive experiments conducted on six datasets and six basic models suggest that DeFTA not only exhibits comparable performance with FedAvg in a more realistic setting, but also achieves remarkable resilience even when 67% of workers are malicious.

Efficacy and tolerability of tirbanibulin 1% ointment in the treatment of cancerization field: a real-life Italian multicenter observational study of 250 patients.

Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp. We performed a multicenter retrospective study involving 15 dermatologic units in Italy to investigate the efficacy and tolerability of tirbanibulin in a real-life setting. 250 patients were enrolled. Tirbanibulin, 1% ointment, was applied daily for five consecutive days. The efficacy of treatment was measured with modifications of the Actinic Keratosis Area and Severity Index (AKASI). A satisfactory response was defined by complete (100% reduction in the number of lesions) or partial clearance (75-99%) of treated AKs. Overall, the AKASI score was significantly reduced in the studied population (mean, from 4.1 ± 2.7 to 1.4 ± 1.5; P < 0.001). A satisfactory response was observed in 222 (88.8%) cases. The proportion of satisfactory responses was higher when follow-up was performed after 8 weeks (34/35, 97.1%). The reduction in AKASI was significant in patients with Olsen grade II or III lesions (from 5.3 ± 2.8 to 1.6 ± 1.6; P < 0.001). A satisfactory response was observed in 91/104 (87.5%) cases. AKASI reduction was also significant in patients with trunk or limb AKs (from 7.0 ± 1.3 to 2.0 ± 1.6; P = 0.018) since a satisfactory response was observed in 7/8 (87.5%) cases. Tirbanibulin was well tolerated; all adverse events (AEs) included transient local reactions at the site of treatment. Overall, 231 patients had at least one AE. Only 7 (2.8%) grade 4 AEs were recorded. Our retrospective study confirmed that tirbanibulin 1% ointment is effective and well tolerated in a real-life setting and is also promising for Olsen grade II and grade III AKs and AKs localized on difficult-to-treat areas.