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AmberTools is a free and open-source collection of programs used to set up, run, and analyze molecular simulations. The newer features contained within AmberTools23 are briefly described in this Application note.

Abstract Background Chronic pain and inflammation are common features of rheumatic conditions such as Psoriatic Arthritis (PsA) and Axial Spondyloarthritis (axSpA), often needing prolonged medication treatment for effective management. Maintaining drug retention is essential for both achieving disease control and improving patients' quality of life. This study investigates the influence of pain catastrophizing, a psychological response to pain, on the drug retention rates of PsA and axSpA patients. Methods A two-year prospective multicenter observational study involved 135 PsA and 71 axSpA patients. Pain Catastrophizing Scale (PCS) was employed to assess pain catastrophizing. Univariable and multivariable regression analyses were utilized to identify factors associated with drug retention. Results In the PsA group, patients early discontinuing therapy showed higher baseline disease activity as well as higher incidence of comorbid fibromyalgia. Notably, pain catastrophizing, specifically the domains of Helplessness, Magnification, and Rumination, were significantly elevated in PsA patients who interrupted the treatment. Multivariable analysis confirmed pain catastrophizing as an independent predictor of drug suspension within two years. In axSpA, drug discontinuation was associated with female gender, shorter disease duration, higher baseline disease activity as well as elevated levels of pain catastrophizing. Univariable analysis supported the role of pain catastrophizing, including its domains, as predictors of treatment interruption. However, limited events in axSpA patients precluded a multivariate analysis. Conclusion This prospective study emphasizes the impact of pain catastrophizing on drug retention in patients with PsA and axSpA.

Pronunciation is taught primarily at the elementary level. It is a skill that students should master throughout their studies so that they can express their opinions clearly. This study aimed to identify Grade 9 students’ mispronounced words and their causes, level of pronunciation, and the exposure of students in pronunciation using the poem titled The Chaos written by Gerard Nolst Trenité. The researchers used a purposive sampling technique by acceptable pronunciation standards to select the respondents who are in level 1 from Grade 9 students in a selected private school in San Jose del Monte, Bulacan. This study utilized Patole’s English Pronunciation Problems to classify the mispronounced words followed by a focus group discussion. The results showed that irregular pronunciation was the most common pronunciation problem encountered by the students. Additionally, two respondents stepped on level 2 and one respondent stepped on level 3 wherein the respondents agreed that companions are a great help for them to pronounce the words because they can correct it right away.

Abstract Purpose Implanted devices used in metastatic spine tumor surgery (MSTS) include pedicle screws, fixation plates, fixation rods, and interbody devices. A material to be used to fabricate any of these devices should possess an array of properties, which include biocompatibility, no toxicity, bioactivity, low wear rate, low to moderate incidence of artifacts during imaging, tensile strength and modulus that are comparable to those of cortical bone, high fatigue strength/long fatigue life, minimal or no negative impact on radiotherapy (RT) planning and delivery, and high capability for fusion to the contiguous bone. The shortcomings of Ti6Al4V alloy for these applications with respect to these desirable properties are well recognized, opening the field for an investigation about novel biomaterials that could replace the current gold standard. Previously published reviews on this topic have exhibited significant shortcomings in the studies they included, such as a small, heterogenous sample size and the lack of a cost-benefit analysis, extremely useful to understand the practical possibility of applying a novel material on a large scale. Therefore, this review aims to collect information about the clinical performance of these biomaterials from the most recent literature, with the objective of deliberating which could potentially be better than titanium in the future, with particular attention to safety, artifact production and radiotherapy planning interference. The significant promise showed by analyzing the clinical performance of these devices warrants further research through prospective studies with a larger sample size also taking into account each aspect of the production and use of such materials. Methods The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used to improve the reporting of the review. The search was performed from March 2022 to September 2023. Results At the end of the screening process, 20 articles were considered eligible for this study. Polyetheretherketone (PEEK), Carbon-fibre reinforced polyetheretherketone (CFR-PEEK), long carbon fiber reinforced polymer (LCFRP), Polymethylmethacrylate (PMMA), and carbon screw and rods were used in the included studies. Conclusion CFR-PEEK displays a noninferior safety and efficacy profile to titanium implanted devices. However, it also has other advantages. By decreasing artifact production, it is able to increase detection of local tumor recurrence and decrease radiotherapy dose perturbation, ultimately bettering prognosis for patients necessitating adjuvant treatment. Nonetheless, its drawbacks have not been explored fully and still require further investigation in future studies. This does not exclude the fact that CFR-PEEK could be a valid alternative to titanium in the near future.

Summary:. Blindness from hyaluronic acid filler injections is an uncommon but devastating complication. We present a case of blindness related to a “skin booster.” It is often assumed that skin boosters have no risk of visual problems, and this case underlines the need to understand products’ rheology and chemistry. Given the lack of agreed consensus in bedside and secondary care management, it is important to report and describe all cases of vision loss caused by fillers, including assessment and management, to allow understanding of what may give rise to better outcomes.

IntroductionCystic Fibrosis (CF) is a genetic disease due to loss-of-function mutations of the CFTR channel. F508del is the most frequent mutation (70% of alleles in Italy), while other mutations have much lower frequency. Among them, G85E (0.4% frequency globally, 1.13% in Italy) emerges as a mutation characterized by a severe CFTR folding and trafficking defect.MethodsTo investigate the pharmacological responsiveness of the G85E-CFTR variant, we performed a functional and biochemical characterization in heterologous expression systems and ex vivo models based on patient-derived human nasal epithelial cells (HNEC).ResultsOur study demonstrated that treatment of primary airway cells with elexacaftor and tezacaftor causes a significant (although modest) rescue of CFTR function, that reaches 15%–25% of the activity measured in non-CF epithelia. A detrimental effect of chronic treatment with ivacaftor, further limiting G85E rescue, was also observed. A higher rescue of CFTR function, up to 25%–35% of the normal CFTR activity, with no evidence of negative effects upon chronic potentiator treatment, can be achieved by combining elexacaftor with ARN23765, a novel type 1 corrector endowed with very high potency. Importantly, dose-response relationships suggest that G85E might alter the binding of type 1 correctors, possibly affecting their affinity for the target.DiscussionIn conclusion, our studies suggest that novel combinations of modulators, endowed with higher efficacy leading to increased rescue of G85E-CFTR, are needed to improve the clinical benefit in patients for this variant.

Key Clinical Message Gallstones, microlithiasis, gallbladder sludge, and micro‐gallbladder are frequently reported in cystic fibrosis patients, and modulators could modify gallbladder disease, probably reducing biliary secretions viscosity.

The theoretical reflection on the nature of school algebra and the development of algebraic thinking from the first educational levels is a relevant topic in mathematics education. In this paper, we first summarize and clarify the positions held on this topic by two theoretical frameworks: the Theory of Objectification and the Onto-semiotic Approach. We identify concordances and complementarities in the respective conceptions of algebra and of the processes of developing algebraic thinking, as a result of applying these frameworks to analyse some students' responses to a task on numerical patterns. We also analyse and compare the didactic models proposed in both theoretical frameworks for developing algebraic thinking. The analysis of the algebraic thinking and learning episodes is also used to illustrate a general discussion on the identity and boundaries of these theoretical frameworks and the possibilities of coordination and integration.

Abstract Increasing evidence suggests that the cerebellum may have a role in the pathophysiology of Parkinson’s disease (PD). Hence, the scope of this study was to investigate whether there are structural and functional alterations of the cerebellum and whether they correlate with motor and non-motor symptoms in early PD patients. Seventy-six patients with early PD and thirty-one age and sex-matched healthy subjects (HS) were enrolled and underwent a 3 T magnetic resonance imaging (MRI) protocol. The following MRI analyses were performed: (1) volumes of 5 cerebellar regions of interest (sensorimotor and cognitive cerebellum, dentate, interposed, and fastigial nuclei); (2) microstructural integrity of the cerebellar white matter connections (inferior, middle, and superior cerebellar peduncles); (3) functional connectivity at rest of the 5 regions of interest already described in point 1 with the rest of brain. Compared to controls, early PD patients showed a significant decrease in gray matter volume of the dentate, interposed and fastigial nuclei, bilaterally. They also showed abnormal, bilateral white matter microstructural integrity in all 3 cerebellar peduncles. Functional connectivity of the 5 cerebellar regions of interest with several areas in the midbrain, basal ganglia and cerebral cortex was altered. Finally, there was a positive correlation between abnormal functional connectivity of the fastigial nucleus with the volume of the nucleus itself and a negative correlation with axial symptoms severity. Our results showed that structural and functional alterations of the cerebellum are present in PD patients and these changes contribute to the pathophysiology of PD in the early phase.

Background: Catheter ablation atrial fibrillation (AF) is effective, but 20% to 40% of patients will require a repeat ablation. The role of more than 1 repeat ablation is not well known. Objectives: The purpose of this study was to evaluate the effectiveness and incremental benefits of multiple repeat catheter ablations to treat AF in patients. Methods: We retrospectively included patients who underwent their first, second, third, and fourth AF ablation between 2004 and 2019. They were monitored with a 24-to-48-hour Holter every 3 months postablation the first year and every 6 to 12 months thereafter. Recurrence was defined as documented atrial arrhythmia >30 seconds. Outcomes are analyzed by Kaplan-Meier curves and compared by log rank test. Results: We included a total of 2,194 patients (64% with paroxysmal and 36% with nonparoxysmal AF). Mean age was 71 ± 10 years; 67% were male. After 1 ablation, freedom from AF was 52%. Among those 1,052 patients who had recurrences, 576 (55%) underwent a second ablation, 103 (10%) underwent a third procedure, and 20 (2%) underwent a fourth. Success rates for the second, third, and fourth ablation were 57%, 60%, and 40%, respectively, at 5-year follow-up. After the second ablation, freedom from AF in our entire cohort increased from 52% to 66%, with marginal changes after the third (67%) and fourth (67%) procedures. Conclusions: Although repeated ablations demonstrated significant benefits at the individual level, the success rate may drop off after a third. The overall success of the initial cohort was not significantly influenced by the success rates of multiple follow-up ablations.

Interactions between macromolecules orchestrate many mechanobiology processes. However, progress in the field has often been hindered by the monetary and time costs of obtaining reliable experimental structures. In recent years, deep-learning methods, such as AlphaFold, have democratized access to high-quality predictions of the structural properties of proteins and other macromolecules. The newest implementation, AlphaFold 3, significantly expands the applications of its predecessor, AlphaFold 2, by incorporating reliable models for small molecules and nucleic acids and enhancing the prediction of macromolecular complexes. While several limitations still exist, the continuous improvement of machine learning methods like AlphaFold is producing a significant revolution in the field. The possibility of easily accessing structural predictions of biomolecular complexes may create substantial impacts in mechanobiology. Indeed, structural studies are at the basis of several applications in the field, such as drug discovery for mechanosensing proteins, development of mechanotherapy, understanding the mechanotransduction mechanisms and the mechanistic basis of diseases, or designing biomaterials for tissue engineering.

Abstract Ferredoxin‐2 (FDX2) is an electron transport protein required for iron–sulfur clusters biosynthesis. Pathogenic variants in FDX2 have been associated with autosomal recessive FDX2‐related disorder characterized by mitochondrial myopathy with or without optic atrophy and leukoencephalopathy. We described a new case harboring compound heterozygous variants in FDX2 who presented with recurrent rhabdomyolysis with severe episodes affecting respiratory muscle. Biochemical analysis of the patients revealed hyperexcretion of 2‐hydroxyadipic acid, along with previously reported biochemical abnormalities. The proband demonstrated increased lactate and creatine kinase (CK) with increased amount of glucose infusion. Lactate and CK drastically decreased when parenteral nutrition containing high protein and lipid contents with low glucose was initiated. Overall, we described a new case of FDX2‐related disorder and compare clinical, biochemical and molecular findings with previously reported cases. We demonstrated that 2‐hydroxyadipic acid biomarker could be used as an adjunct biomarker for FDX2‐related disorder and the use of parenteral nutrition as a treatment option for the patient with FDX2‐related disorder during rhabdomyolysis episode. Highlights 2‐Hydroxyadipic acid can serve as a potential adjunct biomarker for iron‐sulfur assembly defects and lipoic acid biosynthesis disorders. Parenteral nutrition containing high lipid and protein content could be used to reverse acute rhabdomyolysis episodes in the patients with FDX2‐related disorder.

Abstract CD19‐targeting treatments have shown promise in relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL). Loncastuximab tesirine (loncastuximab tesirine‐lpyl [Lonca]) is a CD19‐targeting antibody‐drug conjugate indicated for R/R DLBCL after at least two systemic treatments. CD19 expression was evaluated in patients receiving Lonca in the LOTIS‐2 clinical trial with available tissue samples obtained after last systemic therapy/before Lonca treatment. Lonca cytotoxicity was evaluated in a panel of six lymphoma cell lines with various CD19 expression levels. Quantitative systems pharmacology (QSP) modelling was used to predict Lonca responses. Lonca responses were seen in patients across all CD19 expression levels, including patients with low/no detectable CD19 expression and H‐scores at baseline. Similarly, Lonca induced cytotoxicity in cell lines with different levels of CD19 expression, including one with very low expression. QSP modelling predicted that CD19 expression by immunohistochemistry alone does not predict Lonca response, whereas inclusion of CD19 surface density improved response prediction. Virtual patients responded to Lonca with estimated CD19 as low as 1000 molecules/cell of CD19, normally below the immunohistochemistry detection level. We found Lonca is an effective treatment for R/R DLBCL regardless of CD19 expression by immunohistochemistry. These results provide the basis for future studies addressing CD19‐targeted agent sequencing.

Abstract Upcoding in Medicare has been a topic of interest to economists and policy makers for nearly 40 years. While upcoding is generally understood as “billing for services at higher level of complexity than the service actually pro- vided or documented,” it has a wide range of definitions within the literature. This is largely because the financial incentives across programs and aspects under the coding control of billing specialists and providers are different, and have evolved substantially over time, as has the published literature. Arguably, the primary importance of analyzing upcoding in different parts of Medicare is to inform policy makers on the magnitude of the process and to suggest approaches to mitigate the level of upcoding. Financial estimates for upcoding in traditional Medicare (Medicare Parts A and B), are highly variable, in part reflecting differences in methodology for each of the services covered. To resolve this variability, we used summaries of audit data from the Comprehensive Error Rate Testing program for the period 2010–2019. This program uses the same methodology across all forms of service in Medicare Parts A and B, allowing direct comparisons of upcoding magnitude. On average, upcoding for hospitalization under Part A represents $656 million annually (or 0.53% of total Part A annual expenditures) during our sample period, while up- coding for physician services under Part B is $2.38 billion annually (or 2.43% of Part B annual expenditures). These numbers compare to the recent consistent estimates from multiple different entities putting upcoding in Medicare Part C at $10–15 billion annually (or approximately 2.8–4.2% of Part C annual expenditures). Upcoding for hospitalization under Medicare Part A is small, relative to overall upcoding expenditures.

Abstract The design, analysis, fabrication, and characterization of two distinct MEMS rotational structures are provided; these structures include a classical symmetrical lancet structure and a novel symmetrical C-shaped structure provided with a tilted arm, and both are actuated by thermal actuators. Our proposed C-shaped structure implemented a curved beam mechanism to enhance the movement delivered by the thermal actuators. The geometrical parameters of our proposed device were optimized using the design of experiment (DOE) method. Furthermore, the analytical modeling based on Castigliano’s second theorem and the simulations based on the finite element method (FEM) were used to predict the behavior of the symmetrical C-shaped structure; the results were in good agreement with each other. The MEMS-based rotational structures were fabricated on silicon-on-insulator (SOI) wafers using bulk micromachining technology and deep reactive ion etching (DRIE) processes. The fabricated devices underwent experimental characterization; our results showed that our proposed MEMS rotational structure exhibited a 28% improvement in the delivered displacement compared to the symmetrical lancet structure. Furthermore, the experimental results showed good agreement with those obtained from numerical analysis. Our proposed structures have potential applications in a variety of MEMS devices, including accelerometers, gyroscopes, and resonators, due to their ability to maximize displacement and thus enhance sensitivity.

This study contributes to the literature on the role of communities of learners in the professional development of physics teachers. It offers insights from the "Collabora--A Community of Learners on Laboratory Work" program, designed to enhance the use of laboratories in secondary school physics teaching. The program's foundation rested upon two pillars: a learning community approach and action research, grounded in the findings of physics education research. Furthermore, the program was structured to encompass the core features of effective professional development as outlined in the literature (content focus, active learning opportunities, coherence with teachers' needs, and sufficient duration). The program spanned 2 years. During the first year, teachers engaged with and discussed different types of experiments, reflected on the assessment of scientific practices, and participated in action research aimed at improving laboratory activities in their classrooms. In the second year, they focused on integrating laboratory work within teaching-learning sequences developed through a backward design process. The research questions of this study were centered on examining the role and relevance of program features, with particular emphasis on the learning community and action research components, and on investigating the changes reported by teachers as a result of participating in the program. The findings emphasize the pivotal role of the teacher community, with reciprocal training identified as the "truly developmental" element. Moreover, they corroborate the relevance of action research in fostering a sense of ownership of research-based innovations. Over the course of the program, teachers reported changes in the personal domain, in the domain of practice, and, particularly in the second year, also in the domain of student outcomes. These changes included the use of different types of experiments, a greater sense of self-efficacy in the laboratory, and an increased focus on the design and assessment of laboratory work. We studied changes through a "growth" lens, both at the group level and within a subset of individual case studies. The latter analysis highlights different possible productive pathways to teachers' growth, supporting a view of teacher professional development as complex and multifaceted. The program structure facilitated the processes of" enactment" and "reflection" that mediated the various changes.

Background Receptor activator of nuclear factor kappa-B ligand (RANKL) can directly promote tumor growth and indirectly support tumor immune evasion by altering the tumor microenvironment and immune cell responses. This study aimed to assess the prognostic significance of soluble RANKL in patients with advanced non-small cell lung cancer (NSCLC) receiving programmed cell death 1 (PD1)/programmed death-ligand 1 (PDL1) checkpoint inhibitor therapy.Methods Plasma RANKL levels were measured in 100 patients with advanced NSCLC without bone metastases undergoing monotherapy with PD1/PDL1 checkpoint inhibitors. To establish the optimal cut-off value, we used the Cutoff Finder package in R. Survival curves for four distinct patient groups, according to their RANKL and PDL1 levels (high or low), were generated using the Kaplan-Meier method and compared with the log-rank test. The Cox regression model calculated HRs and 95% CIs for overall survival (OS) and progression-free survival (PFS).Results The optimal RANKL cut-off was established at 280.4 pg/mL, categorizing patients into groups with high or low RANKL levels. A significant association was observed between increased RANKL concentrations and decreased survival rates at 24 months, only within the subgroup expressing high levels of PDL1 (p=0.002). Additionally, low RANKL levels in conjunction with elevated PDL1 expression correlated with improved PFS (median 22 months, 95% CI 6.70 to 50 vs median 4 months, 95% CI 3.0 to 7.30, p=0.009) and OS (median 26 months, 95% CI 20 to not reached vs median 7 months, 95% CI 6 to 13, p=0.003), indicating RANKL’s potential as an indicator of adverse prognosis in these patients. Multivariate analysis identified RANKL as an independent negative prognostic factor for both PFS and OS, regardless of other clinicopathological features.Conclusion These results highlight the prognostic and predictive value of RANKL specifically in patients with high PDL1 expression.

Abstract Assisted reproductive techniques are routinely used in livestock species to increase and enhance productivity. Ovarian hyperstimulation is a process that currently relies on administering pituitary‐derived follicle‐stimulating hormone (FSH) or equine chorionic gonadotropin in combination with other hormones to promote the maturation of multiple follicles and thereby achieve superovulation. The use of partially purified preparations of FSH extracted from natural sources is associated with suboptimal and variable results. Recombinant FSH (rFSH) has been produced in a variety of heterologous organisms. However, attaining a bioactive rFSH of high quality and at low cost for use in livestock remains challenging. Here we report the production and characterization of a single chain bovine rFSH consisting of the β‐ and α‐subunit fused by a polypeptide linker (scbFSH) using Leishmania tarentolae as heterologous expression system. This unicellular eukaryote is non‐pathogenic to mammals, can be grown in bioreactors using simple and inexpensive semisynthetic media at 26°C and does not require CO2 or bovine serum supplementation. Stable cell lines expressing scbFSH in an inducible fashion were generated and characterized for their productivity. Different culture conditions and purification procedures were evaluated, and the recombinant product was biochemically and biologically characterized, including bioassays in an animal model. The results demonstrate that L. tarentolae is a suitable host for producing a homogeneous, glycosylated and biologically active form of scbFSH with a reasonable yield.

This study provides an in-depth analysis of the intersection between artificial intelligence (AI) and fashion, focusing on the potentials and ethical challenges related to the intensive use of large datasets. Using methodologies such as “Envisioning” and the “Scenario Planning Model”, the aim is to develop clear and structured approaches to the deployment of AI in the fashion industry, exploring how this technology can transform and enrich the creative process, extending human capabilities. Among the main ethical challenges are training on culturally connoted data, which risks introducing formative bias, and the need to explain AI processes and decisions in understandable terms (explainability). The possible formalization of AI methods to make their processes and results formal is also discussed. The potential capabilities of these technologies to overcome the limits of human intellect are also considered. The conclusions highlight the importance of a balance between technological innovation and ethical considerations to promote ongoing dialogue among diverse stakeholders, ensuring that AI in the fashion industry evolves inclusively, ethically, and responsibly, fostering a future where technology and human creativity coexist harmoniously.

The present study pays particular attention to issues of originality, intellectual property, and potential biases in machine learning models. European legislation on AI, along with various legislative acts that have followed this initial attempt at regulation, is examined as an essential reference point for initiating a technologically responsible and sustainable prospective discussion. The article analyzes two main perspectives: the risks of uncontrolled AI growth, with emphasis on the damage to the conceptualization of technological primacy over human cognition, and the opportunities for harmonization between human and AI. These themes are contextualized in relation to technological development, regulatory policies, consumer trends, and social values.

AbstractBackground The Loggerhead sea turtle (Caretta caretta) is a marine reptile belonging to a monophyletic group of chelonians. As these animals are long-lived, they have the ability to accumulate pollutants.Aim To collect epidemiological data on toxic metals in marine Loggerhead sea turtles.Materials and Methods Forty Loggerhead sea turtles comprising 25 males and 15 females stranded freshly dead between 2013 and 2018 along the coasts of Sicily, Southern Italy, were examined for arsenic, cadmium, and lead accumulation in muscle and adipose tissues by means of a validated ICP-MS method. A modified K index as a growth condition factor, namely Fulton’s K index, was used. Samples were tested in duplicate. A Wilcoxon rank sum test was carried out to evaluate metal contents differences between muscle and adipose tissues and between genders.Results The Fulton’s K index suggested a good body condition of the C. caretta recovered with mean values of 5.34 ± 3.40 (n = 40; ±SD). Detectable concentrations of lead were found in 70% of the samples analysed with mean values of 0.65 ± 1.67 mg/kg wet weight and 0.51 ± 1.29 mg/kg wet weight in muscle and adipose tissues, respectively. No significant differences in arsenic, cadmium, and lead were detected between genders. In addition, no significant correlation was found between modified K index and concentrations of arsenic, cadmium, and lead.Clinical relevance Findings on muscle and adipose tissues suggest chronic exposure of Caretta caretta to high concentrations of especially lead which might negatively affect health and welfare of these marine turtles although body condition was good.

Abstract Agricultural machinery distribution programs are key components of the Philippine government to strengthen its economic productivity. However, concerns were reported that some of the distributed machines were under-utilized or unutilized in their respective farms. This study is focused on the development of a GIS-based model of determining suitable lowland rice areas for two-wheel and four-wheel tractors. A numerical rating system was designed that assigns a suitability score from three criteria, namely slope, road network proximity, and flood risk, based on established scales. Analytical Hierarchy Process was used as an approach to determine the relative influence in which results show that slope has the greatest weight (65%) followed by flood risk and road network proximity with 20% and 15%, respectively. The total suitability score (TSS) is then determined by getting the weighted average of the individual suitability scores. Land suitability mapping on the study area, the CALABARZON region, show that majority of the lowland rice areas are highly suitable for two-wheel and four-wheel tractors (81.39%) while some areas fall under marginal (15.03%) and moderate suitability (3.58%). Geotagged locations of the distributed agricultural tractors from 2015 to 2020 reveal that 78% of the distributed two-wheel tractors and 80% of four-wheel tractors in the region are situated in highly suitable areas. The GIS-based suitability model generated in this study can be utilized by the government to improve its machine distribution programs of two-wheel and four-wheel tractors in lowland rice farms.

Abstract Background Upadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24 weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA. Methods One hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12 weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis. Results At baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs. At 24 weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 ± 13.5 (p