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Background: This safety analysis investigates treatment-emergent mucosal/cutaneous Candida infections in patients treated with ixekizumab (IXE), an anti-interleukin-17A monoclonal antibody, across the approved indications: psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA)., Research Design and Methods: Safety data were pooled from 25 clinical studies. Incidence rates (IRs) are expressed as per 100 patient-years (PY), using the entire duration of exposure., Results: Candida infections had an IR of 1.9 per 100 PY in patients with PsO ( N  = 6892; total PY = 18025.7), 2.0 per 100 PY in patients with PsA ( N  = 1401; total PY = 2247.7), and 1.2 per 100 PY in patients with axSpA ( N  = 932; total PY = 2097.7). The majority of treatment-emergent Candida infections were: (i) experienced only once by patients (IR = 1.3;IR = 1.6;IR = 1.0), (ii) mild/moderate in severity (IR = 0.8/0.9;IR = 1.5/0.4;IR = 0.8/0.5) as opposed to severe (IR = 0.0; IR = 0.0; IR = 0.0), (iii) oral Candida or genital Candida (IR = 0.9/0.6;IR = 1.0/0.7;IR = 0.4/0.6), (iv) marked as recovered/resolved during the studies (89.3%;93.8%;90.3%), (v) not leading to IXE discontinuation (0.0%;0.0%;0.1% discontinued), (vi) managed with topical (34.7%;22.2%;11.5%) or no anti-fungal medications (63.5%;77.8%;80.8%) as opposed to systemic therapies (1.5%;0.0%;7.7%), (vii) typically resolved before next visit., Conclusions: This integrated safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications., Trial Registration: A comprehensive list of the clinical trials and their registration numbers is reported in Table S1 of the supplemental material.

Despite the abundance of data concerning biologic treatments for patients with psoriasis, clinicians are often challenged with discerning the optimal treatment for each patient. To inform this selection, this study explored whether a patient's baseline characteristics or disease profile could predict the likelihood of achieving complete skin clearance with biologic treatment. Machine-learning and other statistical methods were applied to the substantial data collected from patients with moderate-to-severe psoriasis in the ongoing, international, prospective, observational Psoriasis Study of Health Outcomes (PSoHO). The 3 measures of complete skin clearance were a psoriasis area and severity index (PASI)100 response at (a) week 12, (b) month 12, and (c) week 12 and maintain ed at month 6 and month 12 (PASI100 durability). From these real-world data, the absence of nail psoriasis emerged  as the most consistent feature that may be used by clinicians to predict high-level treatment responses with biologic treatment. Other significant predictors of skin clearance with biologic treatments were the absence of hypertension and a lower body surface area affected by psoriasis. Overall, this study evidences the substantial challenge of identifying reliable clinical markers of treatment response for patients with psoriasis and highlights the importance of regular screening for psoriatic nail involvement.

Background: Gluten composition is an important quality parameter of wheat flour. Reversed-phase high-performance liquid chromatography (RP-HPLC) is a state-of-the-art method for its analysis. As this is a very labour-intensive and time-consuming procedure, alternative faster methods are desirable. Enzyme-linked immunosorbent assay (ELISA) is a high-throughput method often used for the analysis of gluten traces in gluten-free products. In this proof-of-principle study, we introduce an experimental triple ELISA for the relative quantitation of gliadins, high-molecular-weight glutenin subunits (HMW-GS) and low-molecular-weight glutenin subunits (LMW-GS) of one wheat flour extract., Results: The results of 80 common wheat flour samples obtained from the triple ELISA and RP-HPLC were correlated. The results for gliadins (r = 0.69) and HMW-GS (r = 0.81) showed a medium and high correlation, respectively. Only a very weak correlation of ELISA and RP-HPLC results was observed for LMW-GS (r = 0.49). Results for glutenins (r = 0.69) and gluten (r = 0.72) had a medium correlation. The gliadin/glutenin ratio (r = 0.47) and LMW-GS/HMW-GS ratio (r = 0.40) showed a weak or no correlation. The gliadin, LMW-GS and gluten contents were lower and the HMW-GS content was higher in the ELISA measurement compared to RP-HPLC., Conclusion: The quantitation of gliadins and HMW-GS by the experimental triple ELISA showed comparable results to RP-HPLC, whereas no strong correlation between the results from the two methods was found for LMW-GS. Overall, the experimental triple ELISA is suitable for relative gluten quantitation, especially for the analysis of large sample sets. Further work will focus on improving the experimental procedure of the ELISA. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Chronic liver disease and cancer are global health challenges. The role of the circadian clock as a regulator of liver physiology and disease is well established in rodents, however, the identity and epigenetic regulation of rhythmically expressed genes in human disease is less well studied. Here we unravel the rhythmic transcriptome and epigenome of human hepatocytes using male human liver chimeric mice. We identify a large number of rhythmically expressed protein coding genes in human hepatocytes of male chimeric mice, which includes key transcription factors, chromatin modifiers, and critical enzymes. We show that hepatitis C virus (HCV) infection, a major cause of liver disease and cancer, perturbs the transcriptome by altering the rhythmicity of the expression of more than 1000 genes, and affects the epigenome, leading to an activation of critical pathways mediating metabolic alterations, fibrosis, and cancer. HCV-perturbed rhythmic pathways remain dysregulated in patients with advanced liver disease. Collectively, these data support a role for virus-induced perturbation of the hepatic rhythmic transcriptome and pathways in cancer development and may provide opportunities for cancer prevention and biomarkers to predict HCC risk., (© 2024. The Author(s).)

Background & Aims: Liver fibrosis is the major driver for hepatocellular carcinoma and liver disease related death. Approved anti-fibrotic therapies are absent and compounds in development have limited efficacy. Increased TGF-β signaling drives collagen deposition by hepatic stellate cells (HSC)/myofibroblasts. Here, we aimed to dissect the role of the circadian clock (CC) in controlling TGF-β signaling and liver fibrosis., Methods: Using CC-mutant mice, enriched HSCs and myofibroblasts obtained from healthy and fibrotic mice in different CC-phases and loss-of-function studies in human hepatocytes and myofibroblasts, we investigated the relationship between CC and TGF-β signaling. We explored hepatocyte-myofibroblast communication through bioinformatic analyses of single-nuclei transcriptomes and validation in cell-based models. Using mouse models for MASH fibrosis and spheroids from patients with liver disease, we performed proof-of-concept studies to validate pharmacological targetability and clinical translatability., Results: We discovered that the CC-oscillator temporally gates TGF-β signaling and this regulation is broken in fibrosis. We demonstrate that HSCs and myofibroblasts contain a functional CC with rhythmic expression of numerous genes, including fibrogenic genes. Perturbation studies in hepatocytes and myofibroblasts revealed a reciprocal relationship between TGF-β-activation and CC perturbation, which was confirmed in patient-derived ex vivo and in vivo models. Pharmacological modulation of CC-TGF-β signaling inhibited fibrosis in mouse models in vivo as well as patient-derived liver spheroids., Conclusion: The CC regulates TGF-β signaling, and the breakdown of this control is associated with liver fibrosis in patients. Pharmacological proof-of-concept studies across different models uncover the CC as a therapeutic candidate target for liver fibrosis - a rising global unmet medical need., Impact and Implications: Liver fibrosis due to metabolic diseases is a global health challenge. Many liver functions are rhythmic throughout the day being controlled by the circadian clock (CC). Here we demonstrate that the regulation of the CC is perturbed upon chronic liver injury and this perturbation contributes to fibrotic disease. By showing that a compound targeting the CC improves liver fibrosis in patient-derived models, this study provides a novel therapeutic candidate strategy to treat fibrosis in patients. Additional studies will be needed for clinical translation. Since the findings uncovers a previously undiscovered profibrotic mechanism and therapeutic target, the study is of interest for scientists investigating liver disease, clinical hepatologists and drug developers., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: Currently, in the treatment of moderate-to-severe psoriasis (PsO) there is a lack of evidence demonstrating optimal biologic treatment response with respect to disease duration. The aim of this post-hoc analysis, using real world data from the Psoriasis Study of Health Outcomes (PSoHO), is to provide evidence if early intervention with biologics is associated with better treatment outcomes and if there is any difference among drug classes or individual biologics., Materials and Methods: For this post-hoc analysis patients were categorised into two subgroups according to shorter (≤2 years) or longer (>2 years) disease duration. Analysis was performed on anti-interleukin (IL)-17A cohort vs other biologics cohort, anti-IL-17A vs other drug classes, and pairwise comparisons of ixekizumab vs individual biologics, provided that the statistical models converged. Analysis investigated the association of disease duration with the proportion of patients achieving 100% improvement in Psoriasis Area Severity Index score (PASI 100) at week 12. Adjusted comparative analyses, reported as odds ratio (OR), were performed using Frequentist Model Averaging (FMA) for each cohort or treatments within each subcategory of the subgroups., Results: At week 12, anti-IL-17A and other biologics cohorts displayed minimal differences in numerical response rate for PASI 100 with respect to disease duration. The anti-IL-17A cohort showed a higher numerical PASI 100 response rate compared to the other biologic cohort irrespective of disease duration (≤2 years: 36.7% vs 21.8%; >2 years: 35.8% vs 21.9%)., Conclusion: Overall, the results do not clearly indicate that treating patients early is critical in achieving optimal patient outcomes. Furthermore, patients treated with ixekizumab show numerically higher response rates relative to other individual biologics irrespective of disease duration.

Introduction: Immune checkpoint inhibitor (ICI)-based combinations have revolutionized the management of first-line metastatic renal cell carcinoma (mRCC) by improving patient survival. Large phase 3 randomized trials assessing ICI-based combinations have reported complete response (CR) rates of 10% to 18% in the first-line setting. However, there is a scarcity of data about the effect of treatment of residual disease regarding CR rates improvement., Materials and Methods: We included retrospectively all consecutive mRCC patients treated in first-line setting at the Institut de Cancérologie Strasbourg Europe with an ICI-based combination involving ICI or TKI, either alone or with added local treatment of residual disease. Patients were characterized according to IMDC risk. Radiologic response was defined according to RECIST v1.1., Results: We enrolled 80 mRCC patients treated with ICI-based combinations between May 2015 and May 2022. The median age was 63 years. Regarding IMDC risk, there were 12 favourable (15%), 50 intermediate (63%), and 18 poor-risk (22%) patients. Forty-seven patients (59%) received ICI + ICI, 24 (30%) received ICI + TKI, and 9 (11%) received another ICI-based therapy. In total, 8 achieved CR (10%), 36 patients (45%) achieved partial response, 23 (29%) achieved stable disease and 12 achieved progressive disease (15%) as the best response with systemic therapy alone. By adding local treatment of residual disease, 11 additional patients (14%) achieved radiological NED. Residual disease resected sites included kidney (n = 6), lymph nodes (n = 5), lung metastases (n = 2) and liver metastases (n = 1)., Conclusions: The resection of residual disease after first-line ICI-based therapy is associated with improved CR rate (CR + NED) in patients with mRCC. These results need to be validated in prospective trial., Patient Summary: In recent years, the advent of immunotherapy has radically changed the management of patients with metastatic kidney cancer. Approximately 10% to 18% of these patients using immune checkpoint inhibitor (ICI)-based combinations no longer have detectable disease on CT scans (complete response). There are currently few data on the use of treatment of residual disease to increase the number of patients in complete response. In this retrospective study, the complete response rate with ICI-based treatment was 10%. When local treatment was added, the number of patients with a complete response increased to 24%. This strategy could increase the number of patients with a prolonged complete response in the future., Competing Interests: Disclosures Fabien Moinard-Butot certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: F. Moinard-Butot has served in advisory roles for BMS. T. Tricard has received travel and accommodation expenses from Janssen. RL. Cazzato has received travel and accommodation expenses from Medtronic, Ipsen and QUANTUM SURGICAL. L. Pierard has received travel and accommodation expenses from Ipsen, Johnson & Johnson, Pfizer, Eli lilly and company, MUNDI PHARMA. V. Lindner reports speaker services for AstraZeneca, Ipsen; and has received travel and accommodation expenses from Ipsen, MSD and Pfizer. S. Martin has served in advisory roles for BMS. M. Burgy has served in advisory roles for Lilly; reports speaker services for BMS and MSD; has received travel and accommodation expenses from Pfizer, Ipsen and MUNDIPHARMA. G. Malouf has served in advisory roles for BMS, MSD and Ipsen; has received travel and accommodation expenses from MSD, Ipsen and BMS. H. Lang reports speaker services for Johnson & Johnson, Astellas pharma. P. Barthélémy has served in advisory roles for Amgen, Astellas, Bayer, BMS, Ipsen, Janssen Cilag, Merck, MSD, Novartis, Gilead Sciences and Pfizer and reports speaker services for AstraZeneca and Seagen. M. Oriel, V. Gaillard, P. Werle, C. Schuster, C. Roy, A. Anthony, C. Bigot, P. Boudier and A. Fritsch have any conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) have a dismal prognosis and any effective neoadjuvant treatment has been validated to date. We aimed to investigate the role of neoadjuvant transarterial chemoembolization (TACE) in upfront resectable HCC larger than 5 cm., Methods: This is a multicentric retrospective study comparing outcomes of large HCC undergoing TACE followed by surgery or liver resection alone before and after propensity-score matching (PSM)., Results: A total of 384 patients were included of whom 60 (15.6%) received TACE. This group did not differ from upfront resected cases neither in terms of disease-free survival (p = 0.246) nor in overall survival (p = 0.276). After PSM, TACE still did not influence long-term outcomes (p = 0.935 and p = 0.172, for DFS and OS respectively). In subgroup analysis, TACE improved OS only in HCC ≥10 cm (p = 0.045), with a borderline significance after portal vein embolization/ligation (p = 0.087) and in single HCC (p = 0.052)., Conclusions: TACE should not be systematically performed in all resectable large HCC. Selected cases could however potentially benefit from this procedure, as patients with huge and single tumors or those necessitating of a PVE., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Given the chronic nature of psoriasis (PsO), more studies are needed that directly compare the effectiveness of different biologics over long observation periods. This study compares the effectiveness and durability through 12 months of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis in a real-world setting., Methods: The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year, prospective, non-interventional cohort study of 1981 adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. The study compares the effectiveness of anti-IL-17A biologics with other approved biologics and provides pairwise comparisons of seven individual biologics versus ixekizumab. The primary outcome was defined as the proportion of patients who had at least a 90% improvement in Psoriasis Area and Severity Index score (PASI90) and/or a score of 0 or 1 in static Physician Global Assessment (sPGA). Secondary objective comparisons included the proportion of patients who achieved PASI90, PASI100, a Dermatology Life Quality Index (DLQI) score of 0 or 1, and three different measures of durability of treatment response. Unadjusted response rates are presented alongside the primary analysis, which uses frequentist model averaging (FMA) to evaluate the adjusted comparative effectiveness., Results: Compared to the other biologics cohort, the anti-IL-17A cohort had a higher response rate (68.0% vs. 65.1%) and significantly higher odds of achieving the primary outcome at month 12. The two cohorts had similar response rates for PASI100 (40.5% and 37.1%) and PASI90 (53.9% and 51.7%) at month 12, with no significant differences between the cohorts in the adjusted analyses. At month 12, the response rates across the individual biologics were 53.5-72.6% for the primary outcome, 27.6-48.3% for PASI100, and 41.7-61.4% for PASI90., Conclusions: These results show the comparative effectiveness of biologics at 6 and 12 months in the real-world setting., (© 2023. The Author(s).)

A novel microsporidium was observed in wild swamp guppies Micropoecilia picta from Levera Pond within Levera National Park Grenada, West Indies. Initial observations indicated similarity with Pseudoloma neurophilia, an important pathogen in zebrafish Danio rerio. P. neurophilia exhibit broad host specifity, including members of the family Poecillidae, and both parasites infect the central nervous system. However, spore morphology and molecular phylogeny based on rDNA showed that the swamp guppy microsporidium (SGM) is distinct from P. neurophilia and related microsporidia (Microsporidium cerebralis and M. luceopercae). Spores of the SGM were smaller than others in the clade (3.6 µm long). Differences were also noted in histology; the SGM formed large aggregates of spores within neural tissues along with a high incidence of numerous smaller aggregates and single spores within the surface tissue along the ventricular spaces that extended submeninx, whereas P. neurophilia and M. cerebralis infect deep into the neuropile and cause associated lesions. Analysis of small subunit ribosomal DNA sequences showed that the SGM was <93% similar to these related microsporidia. Nevertheless, one of 2 commonly used PCR tests for P. neurophilia cross reacted with tissues infected with SGM. These data suggest that there could be other related microsporidia capable of infecting zebrafish and other laboratory fishes that are not being detected by these highly specific assays. Consequently, exclusive use of these PCR tests may not accurately diagnose other related microsporidia infecting animals in laboratory and ornamental fish facilities.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since late 2019 represented an unprecedented public health emergency, which included a need to fully understand coronavirus disease 2019 (COVID-19) across all ages and populations. In response, the US National Institute of Allergy and Infectious Diseases (NIAID) rapidly funded epidemiology studies that monitored COVID-19. However, the diversity and breadth of the populations studied in NIAID-funded COVID-19 observational cohorts were not easy to extrapolate because of siloed approaches to collect and report data within NIAID. Here, we describe the effort to develop a harmonized cohort-study reporting tool that includes common epidemiologic data elements as well as NIAID priorities. We report its implementation to analyze metadata from 58 COVID-19 cohort studies funded from February 2020 to June 2021, and we visualize key metadata, including geographic distribution, study duration, participant demographic characteristics, sample types collected, and scientific priorities addressed. A bibliographic analysis highlights the scientific publications and citations across these funded studies and demonstrates their enormous impact on the COVID-19 field. These analyses highlight how common data elements and reporting tools can assist funding agencies to capture the landscape and potential gaps during public health responses and how they can assist in decision making., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2023.)

In March 2020, the World Health Organization declared COVID-19 a pandemic, which ultimately led to many meat processors temporarily shutting down or reducing processing capacity. This backlog in processing capacity forced many feedlots to retain cattle for longer periods of time and assume the risk of major market fluctuations. The aim of this study was to understand how a dietary insult affects meat quality and muscle metabolism in market-ready steers (590 kg). Sixteen market-ready (590 kg) commercial Angus crossbred steers were subjected to a maintenance diet of either forage or grain for 60 d. Longissimus lumborum (LL) muscle samples were collected immediately postmortem and processed for characteristics reflecting the underlying muscle fiber type and energy state of the tissue. Despite cattle being subjected to a 60-d feeding period, there were no detectable differences ( P  > 0.05) in carcass characteristics, color of lean, or ultimate pH (pH u ). Moreover, our data show that muscle plasticity is rather resilient, as reflected by lack of significance ( P  > 0.05) in oxidative and glycolytic enzymes, myosin heavy chain isoforms (MyHC), myoglobin, and mitochondrial DNA (mtDNA) contents. These data show that market-ready steers are capable of withstanding a low-input feeding strategy up to 60 d without dramatically impacting underlying muscle characteristics and meat quality development., Competing Interests: There is no conflict of interest for all authors that could be perceived as prejudicing the impartiality of the research reported., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science.)

It has been the aim of this study to molecular-taxonomically identify 15 Beauveria isolates collected from different geographical regions and insect hosts in Argentina and to investigate the levels of inter- and intra-specific diversity across this set of isolates. Based on phylogenetic analyses of EF1A-RPB1-RPB2 concatenated genes and BLOC markers, all Beauveria strains were identify as Beauveria bassiana. Within the B. bassiana clades of both phylogenies, isolates from Argentina were not clustered according to geographic origin or host. The 15 fungal isolates were further analyzed by PCR amplification of the intron insertion hot spot region of the nuclear 28S rRNA encoding sequence. By intron sequence and position, seven different group-I intron combinations termed variants A, B1, B2, C, D, E and F were found in the 15 isolates under study. Variants B1/B2 consisting of a single 28Si2 intron were found in ten isolates, whereas variant A occurred twice and variants C through F were unique across the set of isolates under study. The determination of the different introns and intron combinations in the 28S rRNA gene is a powerful tool for achieving infraspecific differentiation of B. bassiana isolates from Argentina., Competing Interests: Declaration of competing interest none., (Copyright © 2024 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: Nail psoriasis is highly prevalent among patients with psoriasis yet remains one of the most challenging areas to treat. To better understand the treatment landscape for psoriatic nail disease, more studies are needed that compare the effectiveness of different biologics for patients with nail psoriasis. This study contributes to this objective by directly comparing the effectiveness of approved biologics in improving nail psoriasis for patients up to month 12 in a real-world setting., Methods: Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year, prospective, non-interventional cohort study of adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. This study assessed the change in modified Nail Psoriasis Severity Index (mNAPSI) score from baseline to months 3, 6 and 12 for 763 patients and compared the effectiveness of anti-interleukin (IL)-17A biologics versus other approved biologics, as well as ixekizumab versus secukinumab, guselkumab, risankizumab and adalimumab. Comparative adjusted analyses used frequentist model averaging (FMA). Least square mean difference (LSMD) in mNAPSI scores are presented as observed., Results: Irrespective of the severity of nail psoriasis at baseline, the anti-IL-17A cohort had greater mean mNAPSI reductions from baseline compared to the other biologics cohort through month 12, reaching significance at months 3 and 6 in the adjusted analysis. For patients with moderate-to-severe nail psoriasis, ixekizumab showed numerically higher mean reductions in mNAPSI scores compared to all other studied biologics, reaching significance versus guselkumab at all timepoints and risankizumab at month 6., Conclusion: This real-world study showed that patients with moderate-to-severe psoriasis and any severity of concomitant nail involvement had significantly faster and more substantial improvements in nail psoriasis up to month 6 in the anti-IL-17A cohort compared to the other biologics cohort. Of the individual biologics studied, ixekizumab showed the highest numerical improvements in nail psoriasis at month 12., Trial Registration: EUPAS24207., (© 2024. The Author(s).)

Understanding universal aspects of quantum dynamics is an unresolved problem in statistical mechanics. In particular, the spin dynamics of the one-dimensional Heisenberg model were conjectured as to belong to the Kardar-Parisi-Zhang (KPZ) universality class based on the scaling of the infinite-temperature spin-spin correlation function. In a chain of 46 superconducting qubits, we studied the probability distribution of the magnetization transferred across the chain's center, [Formula: see text]. The first two moments of [Formula: see text] show superdiffusive behavior, a hallmark of KPZ universality. However, the third and fourth moments ruled out the KPZ conjecture and allow for evaluating other theories. Our results highlight the importance of studying higher moments in determining dynamic universality classes and provide insights into universal behavior in quantum systems.

Engineered dissipative reservoirs have the potential to steer many-body quantum systems toward correlated steady states useful for quantum simulation of high-temperature superconductivity or quantum magnetism. Using up to 49 superconducting qubits, we prepared low-energy states of the transverse-field Ising model through coupling to dissipative auxiliary qubits. In one dimension, we observed long-range quantum correlations and a ground-state fidelity of 0.86 for 18 qubits at the critical point. In two dimensions, we found mutual information that extends beyond nearest neighbors. Lastly, by coupling the system to auxiliaries emulating reservoirs with different chemical potentials, we explored transport in the quantum Heisenberg model. Our results establish engineered dissipation as a scalable alternative to unitary evolution for preparing entangled many-body states on noisy quantum processors.

To promote sustainable consumption, predictors of individuals' intentions need to be understood. Focusing on the example of collaborative consumption, we look at facilitating and inhibiting factors in a preregistered correlational study ( N = 378). We hypothesized the Value-Identity-Personal norm (VIP) model to explain variance in sharing intention. In addition, we expected sharing intentions to be linked to attitudes about (de-)ownership. We also hypothesized self-extension into an object to be a barrier to sharing this object. The results supported all hypotheses: The VIP model and de-ownership orientation were related to sharing intentions. Moreover, self-extension into a car was significantly higher among subsamples of car owners than car sharers. Exploratory findings show that the value-intention link predicted by the VIP can be found for biospheric as well as altruistic values if sharing intentions are assessed with items framed to match these respective values. We discuss implications for attempts to promote sustainable consumption.

Background & Aims: Chronic co-infection with HBV and HDV leads to the most aggressive form of chronic viral hepatitis. To date, no treatment induces efficient viral clearance, and a better characterization of virus-host interactions is required to develop new therapeutic strategies., Methods: Using loss-of-function strategies, we validated the unexpected proviral activity of Janus kinase 1 (JAK1) - a key player in innate immunity - in the HDV life cycle and determined its mechanism of action on HDV through various functional analyses including co-immunoprecipitation assays., Results: We confirmed the key role of JAK1 kinase activity in HDV infection. Moreover, our results suggest that JAK1 inhibition is associated with a modulation of ERK1/2 activation and S-HDAg phosphorylation, which is crucial for viral replication. Finally, we showed that FDA-approved JAK1-specific inhibitors are efficient antivirals in relevant in vitro models including primary human hepatocytes., Conclusions: Taken together, we uncovered JAK1 as a key host factor for HDV replication and a potential target for new antiviral treatment., Impact and Implications: Chronic hepatitis D is the most aggressive form of chronic viral hepatitis. As no curative treatment is currently available, new therapeutic strategies based on host-targeting agents are urgently needed. Here, using loss-of-function strategies, we uncover an unexpected interaction between JAK1, a major player in the innate antiviral response, and HDV infection. We demonstrated that JAK1 kinase activity is crucial for both the phosphorylation of the delta antigen and the replication of the virus. By demonstrating the antiviral potential of several FDA-approved JAK1 inhibitors, our results could pave the way for the development of innovative therapeutic strategies to tackle this global health threat., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Using data from 15 countries, this article investigates whether descriptive and prescriptive gender norms concerning housework and child care (domestic work) changed after the onset of the COVID-19 pandemic. Results of a total of 8,343 participants ( M = 19.95, SD = 1.68) from two comparable student samples suggest that descriptive norms about unpaid domestic work have been affected by the pandemic, with individuals seeing mothers' relative to fathers' share of housework and child care as even larger. Moderation analyses revealed that the effect of the pandemic on descriptive norms about child care decreased with countries' increasing levels of gender equality; countries with stronger gender inequality showed a larger difference between pre- and post-pandemic. This study documents a shift in descriptive norms and discusses implications for gender equality-emphasizing the importance of addressing the additional challenges that mothers face during health-related crises., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Malignant melanoma is a prevalent and aggressive cancer, with globally increasing incidences. While immune checkpoint inhibitors (ICIs) have prolonged the survival of patients with advanced melanoma over the last decade, this improvement comes with the risk of severe immune-related adverse events (irAEs). This systematic review investigates patient baseline characteristics (BCs) as predictive factors for developing severe gastrointestinal, hepatic, and pulmonary irAEs in patients treated with ipilimumab (anti-CTLA-4) and/or nivolumab/pembrolizumab (anti-PD-1). A systematic literature search was conducted in the Ovid databases MEDLINE and EMBASE on 22 April 2022, following the PRISMA guidelines. Out of 1694 articles, 13 were included in the final analysis. We analyzed BCs and the occurrence of severe colitis, hepatitis, and pneumonitis in 22 treatment arms and 3 treatment groups: anti-CTLA-4 ( n = 2904), anti-PD-1 ( n = 1301), or combination therapy ( n = 822). However, missing data preclude a direct comparison of individual BCs and the association to specific irAEs between studies. Descriptive analysis did not identify any significant association between median age, gender distribution, or performance status and severe colitis, hepatitis, or pneumonitis for any of the three treatment groups. We call for greater transparency and standardization in the reporting of patient-specific irAEs.

Hepatocellular carcinoma is usually detected late and therapeutic options are unsatisfactory. Despite marked progress in patient care, HCC remains among the deadliest cancers world-wide. While surgical resection remains a key option for early-stage HCC, the 5-year survival rates after surgical resection are limited. One reason for limited outcomes is the lack of reliable prognostic biomarkers to predict HCC recurrence. HCC prognosis has been shown to correlate with different systemic and pathological markers which are associated with patient survival and HCC recurrence. Liver inflammatory processes offer a large variety of systemic and pathological markers which may be exploited to improve the reliability of prognosis and decision making of liver surgeons and hepatologists. The following review aims to dissect the potential tools, targets and prognostic meaning of inflammatory markers in patients with resectable HCC. We analyze changes in circulant cellular populations and assess inflammatory biomarkers as a surrogate of impaired outcomes and provide an overview on predictive gene expression signatures including inflammatory transcriptional patterns, which are representative of poor survival in these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that author JL, was an Associate Editor and was an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Giannone, Slovic, Pessaux, Schuster, Baumert and Lupberger.)

Objectives: To describe the results of a structured literature review of real-world outcomes with ixekizumab in patients with psoriasis (PsO) and/or psoriatic arthritis (PsA)., Methods: Literature databases, conference proceedings and additional sources were searched for relevant publications. Real-world studies of ≥25 ixekizumab-treated patients with PsO and/or PsA were included. Data on clinical effectiveness, treatment persistence/patterns, economic outcomes, patient-reported outcomes (PROs) and safety were extracted., Results: Fifty-one publications were included. Most studies focused on patients with PsO, and the number of publications with a focus on PROs was low. Studies of treatment patterns found that in general, ixekizumab had similar or better persistence versus other biologics, and rates or risk of switching similar to or less than comparator drugs. Adherence to ixekizumab was high, and patients were less likely to discontinue ixekizumab than other biologics. Ixekizumab was effective in the real world, with a safety profile consistent with that reported in clinical trials., Conclusions: Real-world use of ixekizumab in PsO and PsA is effective and safe, with generally high treatment persistence and adherence. Further work is required to determine the impact of ixekizumab on PROs in PsO, and to gather more data on real-world use of ixekizumab in PsA.

Background: Available network meta-analyses (NMAs) comparing the efficacy of biologics in nail psoriasis (NP) have not included recently approved biologics such as bimekizumab nor have they provided comparisons up to 1 year., Objective: We conducted two NMAs that update and extend results from a previous NMA comparing biologics for achieving complete resolution of NP., Methods: Bayesian NMAs were performed using a generalized linear model with a logit link to model the binary outcome of nail clearance at weeks 24-28 and 48-52., Results: For the NMA at weeks 24-28, which included seven biologics and placebo, the absolute probability of achieving complete resolution of NP was highest for ixekizumab (46.4%; 95% credibility interval [CrI] 35.2-58.0), followed by brodalumab (37.1%; 95% CrI 17.1-62.2) and bimekizumab (30.3%; 95% CrI 12.7-53.9). For the NMA at weeks 48-52, which included six biologics, the absolute probability was highest for ixekizumab (77.2%; 95% CrI 51.1-93.4), followed by adalimumab (75.6%; 95% CrI 61.5-87.3) and brodalumab (71.9%; 95% CrI 38.4-93.2)., Conclusion: Among biologics included in these two NMAs, ixekizumab has the highest absolute probability of achieving complete resolution of NP. Results may help to inform treatment decisions for patients with NP.

A comprehensive in-situ analysis of the developing gluten network during kneading is still a gap in cereal science. With an in-line microscale shear kneading and measuring setup in a conventional rheometer, a first step was taken in previous works toward fully comprehensible gluten network development evaluation. In this work, this setup was extended by an in-situ optical analysis of the evolving gluten network. By connecting a laser scanning microscope with a conventional rheometer, the evaluation of the rheological and optical protein network evolution was possible. An image processing tool for analyzing the protein network was applied for evaluating the gluten network development in a wheat dough during the shear kneading process. This network evaluation was possible without interruption or invasive sample transfer comparing it to former approaches. The shear kneading system was able to produce a fully developed dough matrix within 125% of the reference dough development time in a classical kneader. The calculated network connectivity values from frequency testing ranged over all samples was in good agreement with traditional kneaded wheat dough just over peak consistency., (© 2023 The Authors. Journal of Texture Studies published by Wiley Periodicals LLC.)

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li + PGS ) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li + PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi + Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li + PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li + PGS was positively associated with lithium treatment response in the ConLi + Gen cohort, in both the categorical (P = 9.8 × 10 - 12 , R 2  = 1.9%) and continuous (P = 6.4 × 10 - 9 , R 2  = 2.6%) outcomes. Compared to bipolar patients in the 1 st decile of the risk distribution, individuals in the 10 th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10 - 4 , R 2  = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li + PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment., (© 2023. The Author(s).)

Purpose: Since skin is highly accessible, clinical photography is a useful tool to visually substantiate the real-world effectiveness outcomes of biologic-treated adults with moderate-to-severe psoriasis (PsO). We report the effectiveness and patient-reported outcomes at Week 12 between anti-interleukin (IL)-17A biologics and other biologics as well as ixekizumab and guselkumab in patients with available clinical photography at baseline and Week 12., Patients and Methods: The Psoriasis Study of Health Outcomes (PSoHO) is an international, non-interventional, cohort study investigating the effectiveness of biologics in adults with moderate-to-severe psoriasis at Week 12. Outcomes included the proportion of patients who achieved 90% improvement in Psoriasis Area and Severity Index (PASI90) and/or static Physician Global Assessment (sPGA) 0/1 (primary endpoint), PASI100, PASI90, Dermatology Life Quality Index (DLQI), and Itch Numeric Rating Scale (NRS) (secondary endpoints) at Week 12. Data are reported descriptively., Results: This analysis included 59 biologic-treated (23 anti-IL-17A; 36 other biologics) patients with available clinical photographs from the overall PSoHO study (n=1981). At baseline, the mean (standard deviation [SD]) age was 45.7 (11.1) years, 71.2% were male, 52.5% were bio-experienced and the median (interquartile range) duration of disease was 10.5 (12.4) years. Mean (SD) PASI was 16.9 (9.3) and sPGA was 3.5 (0.8). At Week 12, 65.2%/47.2% of the anti-IL-17A/other biologics cohort achieved the primary outcome. Response rates for PASI90/100 were numerically higher with anti-IL-17A than with other biologics. Patients receiving anti-IL-17A had numerically better outcomes for DLQI 0/1 and Itch NRS than those receiving other biologics at Week 12. Clinical photographs confirmed skin improvements in ixekizumab- and guselkumab-treated patients., Conclusion: This subgroup analysis showed that anti-IL-17A biologics are effective at rapidly improving signs and symptoms of PsO and improving quality of life. Additionally, serial photography provided visual evidence of biologic treatment response over time., Competing Interests: With no relation to the present manuscript Julia-Tatjana Maul has served as advisor and/or received speaking fees and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, BMS, Celgene, Eli Lilly, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, and UCB. Jens Gerwien, Michaela Müller, Alan Brnabic, and Christopher Schuster are employees and minor share holders of Eli Lilly. Tsen-Fang Tsai is an investigator and/or consultant for Boehringer Ingelheim, AbbVie, Bristol-Myers Squibb, Celgene, Eli-Lilly, Janssen-Cilag, Novartis, Pfizer, and Sanofi, outside the submitted work., (© 2023 Travaglini et al.)

(1) Background: The entomopathogenic fungus Metarhizium anisopliae sensu lato forms a species complex, comprising a tight cluster made up of four species, namely M. anisopliae sensu stricto , M. pinghaense , M. robertsii and M. brunneum . Unambiguous species delineation within this "PARB clade" that enables both the taxonomic assignment of new isolates and the identification of potentially new species is highly solicited. (2) Methods: Species-discriminating primer pairs targeting the ribosomal intergenic spacer (rIGS) sequence were designed and a diagnostic PCR protocol established. A partial rIGS sequence, referred to as rIGS-ID800, was introduced as a molecular taxonomic marker for PARB species delineation. (3) Results: PARB species from a validation strain set not implied in primer design were clearly discriminated using the diagnostic PCR protocol developed. Using rIGS-ID800 as a single sequence taxonomic marker gave rise to a higher resolution and statistically better supported delineation of PARB clade species. (4) Conclusions: Reliable species discrimination within the Metarhizium PARB clade is possible through both sequencing-independent diagnostic PCR and sequencing-dependent single marker comparison, both based on the rIGS marker.

Nail psoriasis is a difficult-to-treat manifestation of psoriatic disease affecting up to 80% of patients with psoriatic arthritis (PsA) and 40-60% of patients with plaque psoriasis (PsO). Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of patients with PsA and patients with moderate-to-severe PsO. This narrative review aims to summarize nail psoriasis data generated from IXE clinical trials in patients with PsA (SPIRIT-P1, SPIRIT-P2, and SPIRIT-H2H) and/or moderate-to-severe PsO (UNCOVER-1, -2, -3, IXORA-R, IXORA-S, and IXORA-PEDS) with an emphasis on head-to-head clinical trial data. Across numerous trials explored, IXE treatment was associated with greater improvement in resolution of nail disease versus comparators at week 24, results which were maintained up to and beyond week 52. Additionally, patients experienced higher rates of resolution of nail disease versus comparators at week 24 and maintained high levels of resolution up to week 52 and beyond. In both PsA and PsO, IXE demonstrated efficacy in treating nail psoriasis, and therefore may be an effective therapy option. Trial Registration: ClinicalTrials.gov identifier UNCOVER-1 (NCT01474512), UNCOVER-2 (NCT01597245), UNCOVER-3 (NCT01646177), IXORA-PEDS (NCT03073200), IXORA-S (NCT02561806), IXORA-R (NCT03573323), SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295), SPIRIT-H2H (NCT03151551)., (© 2023. The Author(s).)

Background: Gastric cancer is associated with significant mortality worldwide. Radical gastrectomy with lymphadenectomy is considered the only curative option. Traditionally, these operations are associated with significant morbidity. Laparoscopic gastrectomy (LG) and more recently robotic gastrectomy (RG) techniques have been developed to potentially decrease the perioperative morbidity. We sought to compare oncologic outcomes with laparoscopic and robotic techniques for gastrectomy., Methods: Utilizing the National Cancer Database we identified patients who underwent gastrectomy for adenocarcinoma. Patients were stratified by open, robotic or laparoscopic surgical technique. Open gastrectomy patients were excluded., Results: We identified 1,301 patients who underwent RG and 4,892 LG with median ages of 65 (20-90) and 66 (18-90) respectively, p = 0.02. The mean number of positive lymph nodes were higher in the LG 2.2 ± 4.4 vs RG 1.9 ± 3.8, p = 0.01. The R0 resections were higher in the RG at 94.5% vs 91.9% in LG, p = 0.001. Conversions to open were 7.1% in the RG and 16% in the LG group, p < 0.001. The median length of hospitalization was 8 (6-11) in both groups. There was no difference in the 30-day readmission (p = 0.65), 30-day mortality (p = 0.85) and 90-day mortality (p = 0.34) between groups. The median and overall 5-year survival was 71.3 mo and 56% in the RG and 66.1 mo and 52% in the LG, p = 0.03. Multivariate analysis revealed that age, Charlson-Deyo comorbidity scores, location of gastric cancer, histology grade, pathologic T-stage, pathologic N-stage, surgical margins, and facility volume were all predictors of survival., Conclusions: Robotic and laparoscopic techniques are both acceptable approaches to gastrectomy. However, conversions to open are higher and R0 resections rates are lower in the laparoscopic group. Additionally, a survival benefit is demonstrated in those undergoing robotic gastrectomy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Rapid skin improvement is a key treatment goal of patients with moderate-to-severe psoriasis (PsO)., Objectives: To compare the speed of clinical improvement of approved biologics on the symptoms and signs of psoriasis assessed by patients using the validated Psoriasis Symptoms and Signs Diary (PSSD) through 12 weeks., Methods: Psoriasis Study of Health Outcomes (PSoHO) is an international, prospective, non-interventional study that compares the effectiveness of anti-interleukin (IL)-17A biologics versus other biologics, together with pairwise comparisons of ixekizumab versus five individual biologics in patients with PsO. Using the PSSD 7-day recall period, patients assessed the symptoms (itch, skin tightness, burning, stinging and pain) and signs (dryness, cracking, scaling, shedding/flaking, redness and bleeding) of their psoriasis (0-10). Symptom and sign summary scores (0-100) are derived from the average of individual scores. Percentage change in summary scores and proportion of patients with clinically meaningful improvements (CMI) in PSSD summary and individual scores are evaluated weekly. Longitudinal PSSD data are reported as observed with treatment comparisons analysed using mixed model for repeated measures (MMRM) and generalized linear mixed models (GLMM)., Results: Across cohorts and treatments, eligible patients (n = 1654) had comparable baseline PSSD scores. From Week 1, the anti-IL-17A cohort achieved significantly larger score improvements in PSSD summary scores and a higher proportion of patients showed CMIs compared to the other biologics cohort through 12 weeks. Lower PSSD scores were associated with a greater proportion of patients reporting their psoriasis as no longer impacting their quality-of-life (DLQI 0,1) and a high level of clinical response (PASI100). Results also indicate a relationship between an early CMI in PSSD score at Week 2 and PASI100 score at Week 12., Conclusions: Treatment with anti-IL-17A biologics, particularly ixekizumab, resulted in rapid and sustained patient-reported improvements in psoriasis symptoms and signs compared with other biologics in a real-world setting., (© 2023 Eli Lilly and Co and The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Vascular endothelial growth factor (VEGF) was initially known as vascular permeability factor and identified as a driver of tumour angiogenesis. Recently, its role in supporting an immunosuppressive tumour microenvironment was demonstrated, and anti-VEGF treatment combined with immune checkpoint blockade is currently investigated. Further, beta-adrenergic signalling as a modifier of cancer hallmarks like immune response, angiogenesis and metastasis gained increased attention during past years., Methods: Focusing on the aspect of immunosuppression in upregulated beta-adrenergic signalling, we investigated predictive markers in patients with metastatic melanoma who received bevacizumab monotherapy, a specific VEGF-A binding antibody. We explored the expression of beta-2 adrenergic receptor (β2-AR), interleukin 6-receptor (IL6-R), cyclooxygenase 2 (COX2) and VEGF-A by immunohistochemistry in melanoma to assess the correlation between these proteins in melanoma cells and response to treatment., Results: Strong β2-AR expression in metastases was associated with clinical benefit of bevacizumab. Furthermore, expression of the latter was positively linked to expression of VEGF-A and COX2. β2-AR expression in melanoma metastasis appears to distinguish a subgroup of patients that might benefit from anti-VEGF treatment., Conclusion: Our results strengthen further exploration of anti-VEGF therapy in combination with immune checkpoint blockade in clinical studies and the investigation of β2-AR as predictive marker., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Combining liver resection (LR) with radiofrequency ablation (RFA) is nowadays an accepted option for treating colorectal liver metastases (CRLMs), but the number of lesions ablated is regularly described as a recurrence risk factor. In this study, we report our experience and determine the impact of RFA on long-term outcomes., Method: This is a retrospective study including patients undergoing LR with or without RFA for CRLM. All variables influencing disease-free survival (DFS) and disease-specific survival (DSS) were examined through a Cox regression analysis before and after propensity-score matching (PSM)., Results: Among the 128 patients included, 71 (55.5%) underwent LR alone and 57 (44.5%) underwent LR+RFA. With univariate analysis, LR+RFA showed a significantly worse DFS than LR alone (p = 0.028), which was not confirmed after PSM (p = 0.064). Thermal ablation did not influence DSS before or after matching (p = 0.282 and p = 0.189). When analyzing the subgroups of patients according to number of RFAs performed, no difference in long-term outcomes was observed (after PSM: p = 0.192 for DFS and p = 0.624 for DSS). Analysis of site of recurrence revealed that neither performing an RFA (p = 0.893) nor the number of lesions ablated (p = 0.093, p = 0.550, and p = 0.087 for 1, 2, and ≥ 2 RFAs) were associated with an increased risk of liver-only relapse., Discussion: In the setting of a parenchymal sparing strategy, combining RFA with LR is safe in terms of oncological outcomes. Tumor burden, rather than RFA performed, independently influences risk of recurrence and patient survival., (© 2023. Society of Surgical Oncology.)

Introduction: Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by heterogeneous clinical phenotypes and high symptom burden, especially through itch. Baricitinib (BARI), an oral Janus Kinase 1/2 inhibitor, is approved in Europe, Japan, and other countries, for treatment of adults with moderate-to-severe AD who are candidates for systemic therapy. This post hoc analysis of a Phase 3 topical corticosteroid (TCS) combination therapy trial (BREEZE-AD7) aims to characterize patients who might benefit most from BARI., Method: Classification and regression tree (CART) analysis was used to identify baseline predictors for patients treated with BARI 4-mg, who achieved ≥ 75% improvement in Eczema Area and Severity Index (EASI75), or EASI75 or Itch Numerical Rating Scale (NRS) ≥ 4-point improvement at week 16 (responders), versus non-responders. Subgroup efficacy analyses were performed based on identified predictor variables, combined with Itch NRS < 7/ ≥ 7. Missing data were imputed as non-responder., Results: Baseline body surface area (BSA) was identified by CART as strongest variable predicting response to BARI at week 16, with a cut-off around 40% (BSA ≤ 40%). When combining BSA with itch severity, highest response rates were achieved by BARI patients with BSA ≤ 40%/Itch NRS ≥ 7 at baseline. In this subgroup, 69% and 58% of patients treated with BARI 4-mg achieved EASI75 and Itch NRS ≥ 4-point response at week 16, respectively. While these response rates were 65% and 50% for BARI 4-mg patients with baseline BSA ≤ 40%/Itch NRS < 7, they were 33% and 11% in BSA > 40%/Itch NRS < 7, and 32% and 49% in BSA > 40%/Itch NRS ≥ 7 subgroups, respectively., Conclusion: Using a machine learning approach, patients with moderate-to-severe AD and a BSA affecting 10-40% and Itch NRS ≥ 7 were characterized as likely to benefit most from BARI 4-mg TCS combination therapy. This was confirmed by subgroup analyses, which showed that these patients are most likely to show favorable response rates in improving AD signs and symptoms, specifically itch, after 16 weeks of treatment., (© 2023. The Authors.)

With the increasing number of electrical devices, especially electric vehicles, the need for efficient recycling processes of electric components is on the rise. Mechanical recycling of lithium-ion batteries includes the comminution of the electrodes and sorting the particle mixtures to achieve the highest possible purities of the individual material components (e.g., copper and aluminum). An important part of recycling is the quantitative determination of the yield and recovery rate, which is required to adapt the processes to different feed materials. Since this is usually done by sorting individual particles manually before determining the mass of each material, we developed a novel method for automating this evaluation process. The method is based on detecting the different material particles in images based on simple thresholding techniques and analyzing the correlation of the area of each material in the field of view to the mass in the previously prepared samples. This can then be applied to further samples to determine their mass composition. Using this automated method, the process is accelerated, the accuracy is improved compared to a human operator, and the cost of the evaluation process is reduced.

Introduction: Psoriasis localized at the scalp, face, nails, genitalia, palms, and soles can exacerbate the disease burden. Real-world studies comparing the effectiveness of treatments for these special areas are limited., Methods: Psoriasis Study of Health Outcomes (PSoHO) is an international, prospective, non-interventional, study comparing the effectiveness of anti-interleukin (IL)-17A biologics (ixekizumab and secukinumab) compared to other approved biologics and the pairwise comparative effectiveness of ixekizumab relative to five other individual biologics for patients with moderate-to-severe psoriasis. To determine special area involvement, physicians answered binary questions at baseline and week 12. The proportion of patients who achieved special area clearance at week 12 was assessed. Missing outcome data were imputed as non-response. Comparative treatment analyses were conducted using frequentist model averaging., Results: Of the 1,978 patients included, 83.4% had at least one special area involved at baseline with the scalp (66.7%) as the most frequently affected part, followed by nails (37.9%), face/neck (36.9%), genitalia (25.6%), and palms and/or soles (22.2%). Patients with scalp, nail, or genital, but not palmoplantar or face/neck psoriasis, had significantly higher odds of achieving clearance at week 12 in the anti-IL-17A cohort compared to the other biologics cohort. Patients with scalp psoriasis had a 10-20% higher response rate and significantly greater odds (1.8-2.3) of achieving clearance at week 12 with ixekizumab compared to included biologics., Conclusion: Biologics demonstrate a high level of clearance of special areas at week 12 in a real-world setting. Patients with scalp, nail, or genital involvement have significantly higher odds of clearance at week 12 with anti-IL-17A biologics compared to other biologics., Competing Interests: SP received consulting fees from Abbvie, Almirall, Celgene, Janssen, Leo-pharma, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, Pfizer, Sandoz, UCB; speaker payments from Abbvie, Almirall, Celgene, Janssen, Leo-pharma, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, Pfizer, Sandoz, UCB; support for attending meetings or travel from Abbvie, Almirall, Celgene, Janssen, Leo-pharma, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, Pfizer, Sandoz, UCB. LP received consulting fees from AbbVie, Janssen Biotech, Novartis Pharmaceuticals Corporation, Eli Lilly, Bristol Myers Squibb; payment or honoraria for lecturers or presentations from AbbVie, Janssen Biotech, Novartis Pharmaceuticals Corporation, Eli Lilly and Company, Bristol Myers Squibb; participated on data safety monitoring board or advisory boards of AbbVie, Janssen Biotech, Novartis Pharmaceuticals Corporation, Eli Lilly, Bristol Myers Squibb. The institution of LP received funding for the present study. The institution of PB received funding from Pfizer. PB received consulting fees from LEO Pharma, Pfizer, Sanofi Genzyme, Eli Lilly, Novartis, Celgene, UCB Pharma, Biotest, Boehringer Ingelheim, AbbVie, Amgen, Arena Pharmaceuticals, GSK and Regeneron; received payment or honoraria for lectures and presentations from LEO Pharma, Pfizer, Sanofi Genzyme, Eli Lilly, Novartis, Celgene, UCB Pharma, Biotest, Boehringer Ingelheim, AbbVie, Amgen, Arena Pharmaceuticals, GSK and Regeneron; was a board member of the Austrian Society for Allergology and Immunology. RV was employed by Dermatrials Research Inc. and Venderm Consulting. RV has received grants from Abbvie, Amgen, Arcutis, Bausch, Health, Boehringer, Ingelheim, BMS, Celgene, Centocor, Dermira, Dermavant, Galderma, GlaxoSmithKline, Innovaderm, Janssen, LEO Pharma, Eli Lilly and Company, Mediji, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, Takeda and USB; Consulting fees from Abbvie, Actelion, Amgen, Aralez, Arcutis, Bausch-Health, Boehringer Ingelheim, BMS, Celgene, Cipher, Janssen, Galderma, GSK, Kabo-Care, LEO Pharma, Eli Lilly and Company, Merck, Novartis, Palladin, Pfizer, Sandoz, SUN, UCB and Viatris-Mylan; payment or honoraria for lectures or presentations from Abbvie, Actelion, Amgen, Arcutis, Bausch-Health, BMS, Celgene, Cipher, Janssen, Galderma, GSK, LEO pharma, Eli Lilly and Company, Merck, Novartis, Pfizer, Sun and USB; support for attending meetings or travel from Abbvie, Arcutis, Janssen and UCB. CM is a contractor of HaaPACs GmbH and conducted statistical analysis for this project on behalf of Eli Lilly and Company. NH, NT, GG, and CS are employees and minor shareholders of Eli Lilly and Company. ER is a former employee of Eli Lilly and Company and a minor stockholder and has also been a speaker and consultant for Eli Lilly and Company. The authors declare that this study received funding from Eli Lilly and Company. The funder was involved in study design, analysis and interpretation of data, the writing of this article and the decision to submit it for publication., (Copyright © 2023 Piaserico, Riedl, Pavlovsky, Vender, Mert, Tangsirisap, Haustrup, Gallo, Schuster and Brunner.)

The development of new anti-ureolytic compounds is of great interest due to the newly discovered role of urease inhibitors in crop protection. Purine degradation and the generation of ammonium by urease are required for the full virulence of biotrophic and hemibiotrophic fungal plant pathogens. Accordingly, chemicals displaying urease inhibitor activity may be used as a novel class of fungicides. Several urease inhibitors belonging to different chemical classes are known, and some compounds have been developed as urea fertilizer additives. We tested whether the natural urease inhibitors p -benzoquinone ( p -HQ) and hydroquinone (HQ), as well as the synthetic inhibitors isopropoxy carbonyl phosphoric acid amide (iCPAA), benzyloxy carbonyl phosphoric acid amide (bCPAA), and dipropyl-hexamino-1,3 diphosphazenium chloride (DDC), prevent or delay plant infection caused by pathogens differing in lifestyles and host plants. p -BQ, HQ, and DCC not only protected maize from infection by the hemibiotroph C. graminicola , but also inhibited the infection process of biotrophs such as the wheat powdery mildew fungus Blumeria graminis f. sp. tritici and the broad bean rust fungus Uromyces viciae-fabae . Interestingly, the natural quinone-based compounds even reduced the symptom severity of the necrotrophic fungi, i.e., the grey mold pathogen B. cinerea and the Southern Leaf Spot fungus C. heterostrophus , to some extent. The urease inhibitors p -BQ, HQ, and DCC interfered with appressorial penetration and confirmed the appropriateness of urease inhibitors as novel fungicidal agents.

Drop-on-demand printing using colloidal or pigmented inks is prone to the clogging of printing nozzles, which can lead to positional deviations and inconsistently printed patterns (e.g., data matrix codes, DMCs). However, if such deviations are detected early, they can be useful for determining the state of the print head and planning maintenance operations prior to reaching a printing state where the printed DMCs are unreadable. To realize this predictive maintenance approach, it is necessary to accurately quantify the positional deviation of individually printed dots from the actual target position. Here, we present a comparison of different methods based on affinity transformations and clustering algorithms for calculating the target position from the printed positions and, subsequently, the deviation of both for complete DMCs. Hence, our method focuses on the evaluation of the print quality, not on the decoding of DMCs. We compare our results to a state-of-the-art decoding algorithm, adopted to return the target grid positions, and find that we can determine the occurring deviations with significantly higher accuracy, especially when the printed DMCs are of low quality. The results enable the development of decision systems for predictive maintenance and subsequently the optimization of printing systems.

A wide array of bacteria and fungi are known for their association with pests that impact the health of the olive tree. The latter presents the most economically important cultivation in Tunisia. The microbial diversity associated with olive orchards in Tunisia remains unknown and undetermined. This study investigated microbial diversity to elucidate the microbial interactions that lead to olive disease, and the bio-prospects for potential microbial biocontrol agents associated with insect pests of economic relevance for olive cultivation in the Mediterranean area. Bacterial and fungal isolation was made from soil and olive tree pests. A total of 215 bacterial and fungal strains were randomly isolated from eight different biotopes situated in Sfax (Tunisia), with different management practices. 16S rRNA and ITS gene sequencing were used to identify the microbial community. The majority of the isolated bacteria, Staphylococcus , Bacillus , Alcaligenes , and Providencia , are typical of the olive ecosystem and the most common fungi are Penicillium , Aspergillus , and Cladosporium . The different olive orchards depicted distinct communities, and exhibited dissimilar amounts of bacteria and fungi with distinct ecological functions that could be considered as promising resources in biological control.

Introduction: Meningiomas are mostly benign neoplasms of the central nervous system. Nevertheless there are recurrences in about 20% after surgical resection. Previous studies could reveal several predictors of meningioma recurrence. Tumor progression often is associated with a specific pattern of chromosome losses. Our study investigated the potential function of selected microRNAs as markers of tumor progression., Methods: By real-time polymerase chain reaction the expressions of microRNA 21-3p, 34a-3p, 200a-3p, and 409-3p were analyzed in solid tumor and in blood samples of 51 meningioma patients as well as in blood samples of 20 healthy individuals. Additionally, aberrations of parts of chromosomes 1, 14, 18, and 22 were analyzed by FISH. Tumor and blood samples were statistically analyzed, using Spearman's rank correlation coefficient as well as Mann-Whitney U- and Kruskal-Wallis-Test., Results: MicroRNA 200a showed significantly lower expressions in recurrent meningiomas than in newly diagnosed ones. MicroRNA 409 in meningiomas was correlated significantly with tumor volume and showed a significant negative correlation with patient age. Significance was found between the expression patterns of microRNAs 34a and 200a with the respective aberrations of chromosome 1p and the microRNA 409 with aberration of chromosome 14. In the male cohort the expression of microRNA 200a in blood was significantly upregulated in patients compared to healthy volunteers. By our research the function of microRNA 200a was proved to detect meningioma patients by liquid biopsy., Conclusion: We detected microRNA 200a as a new biomarker to indicate meningioma recurrences. Future transferability to blood could be important for patient follow-up., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Across the globe, men make markedly more money than women, even within the same position. We introduce egalitarian norm messaging as a potential intervention to increase women's salaries and counter the gender pay gap. In two preregistered experiments with seasoned professionals ( N = 435, work experience: M > 8 years, salary negotiations: M > 18 per year), we find a significant gender pay bias-Human Resources (HR) experts offered markedly lower salaries in an online negotiation to (simulated) female versus male candidates with identical qualifications. Moreover, the experiments show that dynamic (Experiments 1a and 2), as well as static egalitarian norm messages (Experiment 1a), increased salary offers to women. Exploratory mediation analyses suggest that the dynamic egalitarian norm effect was driven by HR professionals' feeling of working toward a shared goal of greater equity. A message that merely increased awareness of the pay gap did not elicit this feeling and did not significantly increase salary offers to women but resulted in fairly equal treatment of men and women (Experiment 2). While the egalitarian norm intervention significantly increased salary offers to women, it also unexpectedly reduced offers to men, thereby reversing the gender bias (Experiment 2). We discuss the theoretical contribution with regard to gender pay bias and egalitarian norm interventions, as well as applied implications. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Gluten composition is an important quality parameter for wheat flour, because it is strongly correlated to baking quality. Wheat proteins are commonly extracted stepwise and analysed using RP-HPLC-UV to determine the gluten composition. This procedure is very time-consuming and labour-intensive. Therefore, a new, fast and easy method to quantitate gluten proteins was established using NIR spectroscopy (NIRS). PLS-regression models were calculated containing 207 samples for calibration and 169 for test set validation. Albumin/globulin (ALGL), gluten, gliadin and glutenin content was predicted with a root mean square error of prediction (RMSEP) of 2.01 mg/g, 6.09 mg/g, 4.25 mg/g and 3.50 mg/g, respectively. High-molecular-weight glutenin subunits (HMW-GS) and low-molecular-weight glutenin subunits (LMW-GS) were predicted with a RMSEP of 1.12 mg/g and 2.38 mg/g. The relative error was too high for ALGL, LMW-GS and HMW-GS, but that of gluten, gliadins and glutenins was in a range comparable to the reference method. Therefore, the new NIRS method can be used to estimate the gluten composition of wheat flour, including the gliadin/glutenin and the LMW-GS/HMW-GS ratio., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: In routine clinical care, important treatment outcomes among patients with moderate-to-severe plaque psoriasis (PsO) have been shown to vary according to patient demographics and disease characteristics. This study aimed to provide direct comparative effectiveness data at week 12 between anti-interleukin (IL)-17A biologics relative to other approved biologics for the treatment of PsO across seven clinically relevant patient subgroups in the real-world setting., Methods: From the international, non-interventional Psoriasis Study of Health Outcomes (PSoHO), 1981 patients with moderate-to-severe PsO were grouped a priori according to seven clinically relevant demographic and disease variables with binary categories, which were sex (male or female), age (< 65 or ≥ 65 years), body mass index (≤ 30 or > 30 kg/m 2 ), race (White or Asian), PsO disease duration (< 15 or ≥ 15 years), psoriatic arthritis (PsA) comorbidity (present or absent), and prior biologic use (never or ≥ 1). Across these subgroups, effectiveness was compared between the anti-IL-17A cohort (ixekizumab, secukinumab) versus all other approved biologics and ixekizumab versus five individual biologics. The proportion of patients in each subgroup who achieved 90% improvement in Psoriasis Area and Severity Index (PASI90) and/or static Physician Global Assessment (sPGA) 0/1, PASI100, or PASI90 at week 12 were assessed. Comparative analyses were conducted using frequentist model averaging (FMA). Missing data were imputed using non-responder imputation., Results: Patients in each of the seven subgroups achieved similar response rates to those of the overall treatment cohort, apart from patients with PsA treated with other biologics who had 7-10% lower response rates. Consequently, patients with comorbid PsA had significantly higher odds of achieving skin clearance at week 12 with anti-IL-17A biologics compared to other biologics. Patients in all subgroups had significantly higher odds of achieving PASI90 and/or sPGA (0,1), PASI100, and PASI90 in the anti-IL-17A cohort relative to the other biologics cohort, except for the Asian subgroup. No sex- or age-specific differences in treatment effectiveness after 12 weeks were identified, neither between the treatment cohorts nor between the individual treatment comparisons., Conclusions: Despite relative consistency of comparative treatment effectiveness across subgroups, the presence of comorbid PsA may affect a patient's clinical response to some treatments., (© 2023. The Author(s).)