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Laboratory-scale shallow beds filled with catalyst particles are frequently used in catalyst screening, activity tests and kinetic measurements. Often the experimental data are interpreted with plug flow or differential reactor models. Residence time measurements have shown large deviations from ideal plug flow behavior in shallow beds, indication the presence of axial dispersion effects, i.e. is backmixing and diffusion in the bed. The behavior of laboratory-scale bed reactors was investigated by theoretical considerations of the axial dispersion model and numerical simulations in the Damköhler-Péclet space. The results revealed that large errors in kinetic parameters can appear when the dispersion model is replaced by the plug flow model. This key effect was quantified using the ratio (F) of two Damköhler numbers: the real one, and the one wrongly estimated on experimental data affected by dispersion problems and interpreted with ideal plug-flow approach. Thus, the effect of back-mixing is evaluated varying a single parameter of the kinetic model, namely the rate constant. The conclusions are valid for power-law, Langmuir-Hinshelwood and Eley-Rideal kinetics.

Inspired by the adaptability observed in biological materials, self-assembly processes have attracted significant interest for their potential to yield novel materials with unique properties. However, experimental methods have often fallen short in capturing the molecular details of the assembly process. In this study, we employ a multiscale molecular dynamics simulation approach, complemented by NMR quantification, to investigate the mechanism of self-assembly in a redox-fueled bioinspired system. Contrary to conventional assumptions, we have uncovered a significant role played by the monomer precursor in the assembly process, with its presence varying with concentration and the extent of conversion of the monomer to the dimer. Experimental confirmation through NMR quantification underscores the concentration-dependent incorporation of monomers into the fibrous structures. Furthermore, our simulations also shed light on the diverse intermolecular interactions, including T-shaped and parallel π stacking, as well as hydrogen bonds, in stabilizing the aggregates. Overall, the open conformation of the dimer is preferred within these aggregates. However, inside the aggregates, the distribution of conformations shifts slightly to the closed conformation compared to on the surface. These findings contribute to the growing field of bioinspired materials science by providing valuable mechanistic and structural insights to guide the design and development of self-assembling materials with biomimetic functionalities.

Many therapies are available to treat low-risk superficial basal cell carcinoma (lr-sBCC), which may complicate the shared decision-making (SDM) process.

Biolubricants, plasticizers, bio-based rigid foams, and non-isocyanate polyurethanes can be made in a green way from epoxidized fatty acids. The classical technology for fatty acid epoxidation requires a reaction carrier, which acts as the real epoxidation agent. The process is complicated and involves a safety risk because of the appearance of percarboxylic acids. Therefore, the direct epoxidation of fatty acids in the presence of an immobilized enzyme is an attractive pathway to epoxidized fatty acids. Oleic acid was used as the model compound is this work, and commercial immobilized lipase Novozym 435 was used as the catalyst and hydrogen peroxide as the epoxidation agent. Batch and semibatch operation modes were tested in a laboratory-scale stirred tank reactor. The experimental results showed that almost complete conversions of the double bonds in oleic acid were achievable under isothermal batch and semibatch operation, with low concentrations of ring-opening byproducts. Semibatch operation gave an improvement of the product yield. Mathematical modeling of the experimental data was based on the reaction stoichiometry OA + HP → POA + W and OA + POA → EOA + OA, where OA = oleic acid, HP = hydrogen peroxide, POA = peroleic acid, W = water, and EOA = epoxized OA. Rate equations for the formation of peroleic acid and epoxide were derived, and the numerical values of the kinetic and adsorption parameters were estimated with nonlinear regression analysis. The reactor models consisted of ordinary differential equations, which were solved numerically during the parameter estimation until the optimal parameter values were reached. The model gave a very good description of the experimental data.

Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), drug reactions with eosinophilia and systemic symptoms (DRESS) have been very rarely reported. The objective of this study is to better define the clinical and histologic features, treatment and prognosis of ICI-related DRESS. This retrospective case series was conducted between 01 January 2015 and 31 December 2021 by the dermatology departments of five international networks involved in drug reactions. Inclusion criteria were age ≥18 years old, DRESS with Regiscar score ≥4 (probable or certain) and ICI as a suspect drug. Clinical, biologic and follow-up data were extracted from the medical charts. Thirteen patients were included. The median time to onset was 22 days (3–11). No patients had a high-risk drug introduced in the past 3 months. A majority of patients presented fever (92%), diffuse exanthema (77%) and facial edema (69%). Biologic features included hypereosinophilia in eight patients (61.5%), hyperlymphocytosis in 3 (23%), elevated liver function tests in 11 (85%, grade 1 or 2 in most cases) and renal involvement in 5 (38%). Two patients (15%) had lung involvement. PCR evidence of viral replication was detected in five patients (38.5%). Treatment involved discontinuation of the suspect ICI and systemic steroids with variable dose and duration regimens. Among the four patients in which ipilimumab + nivolumab combination therapy was initially suspected, one was rechallenged with nivolumab monotherapy with good tolerance. Five patients were switched to another anti-PD-1 plus low-dose systemic steroids, with good tolerance in four cases. No patient died because of DRESS. DRESS induced by ICI are rare and of moderate severity. A consensus for management is still pending.

Le prurit concerne plus d’un tiers des patients traités par inhibiteurs de checkpoint immunitaires (ICI) en contexte oncologique, qui peut être à la fois source d’arrêt du traitement ou d’altération importante de la qualité de vie. Il peut être isolé ou s’intégrer dans des dermatoses prurigineuses plus spécifiques. Il impose parfois la mise en place d’une corticothérapie systémique, dont l’impact sur l’efficacité des ICI est débattu. Nous rapportons ici l’intérêt d’un inhibiteur anti IL4 et anti IL13 (dupilumab) dans ce contexte.

•Political variables, particularly multilevel partisan alignment, play a crucial role in shaping extractive foreign direct investment (EFDI) in local jurisdictions, especially in Latin America, where natural resources are abundant and Chinese investment has increased.•The study highlights the strategic preference of Chinese investors for regions where local governance is aligned with the national leadership, aiming to reduce investment uncertainties and enhance operational stability in the extractive industries sector.•This research contributes to the understanding of subnational determinants of foreign investments and suggests that political alignment at both national and subnational levels significantly influences investment flows, providing valuable insights for policymakers and stakeholders in recipient countries.

Background: Rheumatology has experienced notable changes in the last decades. New drugs, including biologic agents and Janus kinase (JAK) inhibitors, have blossomed. Concepts such as window of opportunity, arthralgia suspicious for progression, or difficult-to-treat rheumatoid arthritis (RA) have appeared; and new management approaches and strategies such as treat-to-target have become popular. Statistical learning methods, gene therapy, telemedicine, or precision medicine are other advancements that have gained relevance in the field. To better characterize the research landscape and advances in rheumatology, automatic and efficient approaches based on natural language processing (NLP) should be used.Objectives: The objective of this study is to use topic modeling (TM) techniques to uncover key topics and trends in rheumatology research conducted in the last 23?years.Design: Retrospective study.Methods: This study analyzed 96,004 abstracts published between 2000 and December 31, 2023, drawn from 34 specialized rheumatology journals obtained from PubMed. BERTopic, a novel TM approach that considers semantic relationships among words and their context, was used to uncover topics. Up to 30 different models were trained. Based on the number of topics, outliers, and topic coherence score, two of them were finally selected, and the topics were manually labeled by two rheumatologists. Word clouds and hierarchical clustering visualizations were computed. Finally, hot and cold trends were identified using linear regression models.Results: Abstracts were classified into 45 and 47 topics. The most frequent topics were RA, systemic lupus erythematosus, and osteoarthritis. Expected topics such as COVID-19 or JAK inhibitors were identified after conducting dynamic TM. Topics such as spinal surgery or bone fractures have gained relevance in recent years; however, antiphospholipid syndrome or septic arthritis have lost momentum.Conclusion: Our study utilized advanced NLP techniques to analyze the rheumatology research landscape and identify key themes and emerging trends. The results highlight the dynamic and varied nature of rheumatology research, illustrating how interest in certain topics has shifted over time.

Background: Switching between therapies is a recommended strategy for psoriatic arthritis (PsA) patients who experience treatment failure; however, studies including real-life data are scarce.Objectives: To assess the incidence rate (IR) of switching between biologics and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) due to inefficacy in PsA, and to compare the risk of switching due to inefficacy across different b/tsDMARDs groups.Design: A longitudinal retrospective study, spanning from 2007 to 2022, was conducted on patients with PsA treated with b/tsDMARDs at an outpatient rheumatology clinic.Methods: The primary outcome was switching between b/tsDMARDs due to inefficacy. The independent variable was the exposure to b/tsDMARDs during follow-up. As covariates, clinical, treatment-related, and sociodemographic variables were considered. Survival techniques were run to estimate the IR of switching due to inefficacy per 100 patients*year and confidence interval at 95% (95% CI). Cox multivariate regression analyses were run to assess the risk of b/tsDMARDs switching due to inefficacy, expressed as hazard ratio (HR) and 95% CI.Results: In all, 141 patients were included, with 893.09 patients*year follow-ups. 52.48% of them were females in their fifties. In total, 262 courses of treatment were recorded. During the study period, 56 patients presented 121 switches and 103 related to inefficacy (IR: 11.53 (9.51–13.98)). Tumor necrosis factor-alpha inhibitors (TNFi) showed the lowest IR. In the bivariate analysis, all b/tsDMARDs had more risk of switching compared to TNFi (HR: anti-lL-17 vs TNFi: 2.26 (1.17–4.36); others vs TNFi: 3.21 (1.59–6.45)); however, this statistical significance was no longer present in the multivariate analysis once adjustments were made for the covariates. Still, the final model achieved statistical significance in the following variables: gender, clinical symptoms, prescription year, therapy courses, glucocorticoids, and sulfasalazine.Conclusion: In this study, we did not find differences in the rate of switching due to inefficacy among different groups of b/tsDMARDs. Other concomitant treatments, sociodemographic, and clinical variables were identified as risk factors for switching due to inefficacy.

Tattoos are characterized by the introduction of exogenous pigments into the dermis. Tattoos usually serve cosmetic purposes, although they may have other causes, such as traumatic pigment implants in accidents or medical-related tattoos in the context of radiotherapy. Dermatologic adverse reactions are relatively uncommon, and they include infections, immune-mediated reactions, cutaneous lesions secondary to the Koebner phenomenon, exacerbation of preexisting dermatosis, benign and malignant neoplasms, and a miscellaneous group of dermatologic conditions that may appear in a preexisting tattoo. The aim of this study is to review the types of histopathologic reactions that may appear in a preexisting permanent tattoo.

•Unveiling consequences in South America's environmental governance.•There is a strong link between Chinese FDI and heightened environmental concerns.•Chinese state-backed firms raise environmental worries in extractive industries.•Understanding nuances in Chinese investments for informed environmental governance.•Insights for addressing environmental issues tied to Chinese FDI in South America.

Peripheral membrane proteins bind transiently to membrane surfaces as part of many signaling pathways. The bound proteins perform two-dimensional (2-D) diffusion on the membrane surface during the recruitment function. To better understand the interplay between the 2-D diffusion of these protein domains and their membrane binding modes, we performed multimicrosecond all-atom molecular dynamics simulations of two regulatory domains, a C2 domain and a pleckstrin homology (PH) domain, in their experimentally determined bound configuration to a lipid bilayer. The protein bound configurations are preserved throughout the simulation trajectories. Both protein domains exhibit anomalous diffusion with distinct features in their dynamics that reflect their different modes of binding. An analysis of their diffusive behavior reveals common features with the diffusion of lipid molecules in lipid bilayers, suggesting that the 2-D motion of protein domains bound to the membrane surface is modulated by the viscoelastic nature of the lipid bilayer.

Sugar monomers originating from well-controlled hydrolysis of hemicelluloses appearing in biomass are important platform molecules and they can be further valorized by catalytic hydrogenation, oxidation, and isomerization. Oxidation of sugar monomers with molecular oxygen in the presence of gold catalysts is a green pathway for obtaining sugar acids that are useful for alimentary, pharmaceutical, and construction industries. Catalytic oxidation of sugar mixtures on gold nanoparticles supported on aluminum oxide extrudates was studied in an aqueous environment to reveal the interaction of intrinsic kinetics, catalyst deactivation, and mass transfer effects. The oxidation kinetics of two sugar monomers, arabinose and glucose, and their mixtures in the presence of gold nanoparticles was determined. Several oxidation experiments were conducted in a laboratory-scale semibatch reactor at 70 °C, pH 8, and atmospheric pressure. SpinChem mixing technology was applied to immobilize the catalyst particles in the reactor and to create vigorous turbulence, suppressing external mass transfer limitations around the particles. The reaction kinetics were monitored by measuring the concentrations of the reactants and products by high-performance liquid chromatography (HPLC). The gold catalyst extrudates were characterized with transmission electron microscopy (TEM), scanning electron microscopy (SEM), nitrogen physisorption, and particle size analysis. A decline in the oxidation activity was observed in successive semibatch experiments with recycled catalyst extrudates. It was confirmed by inductively coupled plasma analysis (ICP-OES) that the reason for the deactivation was leaching of gold. The kinetic results revealed strong internal mass transfer limitations inside the pores of the catalyst extrudates. A mathematical model was derived for the reaction kinetics, catalyst deactivation, and internal mass transfer, and the parameters of the model were successfully estimated by nonlinear regression analysis. With the mathematical model, the performance of catalyst particles of different sizes can be predicted, which is important for scale-up and in shifting from discontinuous to continuous oxidation technology in the future.

Introduction: Psoriatic arthritis (PsA) is considered a multifaceted disease, with patients reporting low health-related quality of life (HRQoL). Data on disease burden are substantial and there exists a need for properly designed studies to learn more about the evolution of HRQoL in this condition. This study aims to identify factors associated to HRQoL evolution in PsA patients followed-up in a real-world setting in Spain. Methods: We conducted a retrospective longitudinal observational study including incident patients from the rheumatology outpatient clinic of Hospital Clínico San Carlos (Madrid, Spain), diagnosed for the first time of PsA, defined as having received any ICD9/ICD10 diagnosis code of PsA, from 2007 to 2016, and followed-up until loss of follow-up, death, or November 2017. The influence of demographic and clinical variables in baseline HRQoL [assessed with the Rosser Classification Index (RCI)] was analyzed using bivariable and multivariable generalized linear models. The influence of those variables and of treatment-related factors in repeated measures of HRQoL was analyzed using bivariable and multivariable generalized estimating equations (GEE) models nested by patient. Results: Two hundred and thirty patients were included in the analysis, with 3384 registered visits. At baseline, older age, a previous diagnosis of obesity, and the presence of enthesitis were significantly associated with worse HRQoL. During follow-up, using an exchangeable working correlation structure, the presence of enthesitis was also associated with worse HRQoL, coefficient (95% CI) − 0.006 (− 0.01 to − 0.002), p= 1.00E−03; conversely, treatment with methotrexate or antimalarials was associated with better HRQoL with 0.007 (0.001–0.014), p= 0.020 and 0.003 (0.001–0.005), p= 3.00E−03, respectively. Conclusions: Musculoskeletal manifestations and comorbidities exert a deleterious effect in HRQoL of PsA patients. Therefore, the optimal management of this condition needs to also address these manifestations in order to try to restore the QoL of these patients.

The coffee industry constitutes an important part of the global economy. Developing countries produce over 90% of world coffee production, generating incomes for around 25 million smallholder farmers. The scale of this industry poses a challenge with the generation of residues along with the coffee cultivation and processing chain. Coffee stems, obtained after pruning of coffee trees, are one of those abundant and untapped resources in the coffee supply chain. Their high lignocellulosic content, the low calorific value ranging between 17.5 and 18 MJ kg−1and the low ash content make them a suitable solid fuel for thermochemical conversion, such as gasification. This research evaluates the feasibility of using these residues in small-scale downdraft gasifiers coupled to internal combustion engines for power and low-grade heat generation, using process modelling and the Colombian coffee sector as a case study. The producer gas properties (5.6 MJ Nm−3) and the gasifier’s performance characteristics suggest that this gas could be utilized for power generation. A cogeneration system efficiency of 45.6% could be attainable when the system’s low-grade heat is recovered for external applications, like in the coffee drying stage. An analysis of the energy demand and coffee stems availability within the Colombian coffee sector shows that the biomass production level in medium- to large-scale coffee farms is well matched to their energy demands, offering particularly attractive opportunities to deploy this bioenergy system. This work assesses the feasibility of providing coffee stem–sourced low-carbon energy for global coffee production at relevant operating scales in rural areas.

IMPORTANCE: Persistent radiation-induced alopecia (pRIA) and its management have not been systematically described. OBJECTIVE: To characterize pRIA in patients with primary central nervous system (CNS) tumors or head and neck sarcoma. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of patients from January 1, 2011, to January 30, 2019, was conducted at 2 large tertiary care hospitals and comprehensive cancer centers. Seventy-one children and adults diagnosed with primary CNS tumors or head and neck sarcomas were evaluated for pRIA. MAIN OUTCOMES AND MEASURES: The clinical and trichoscopic features, scalp radiation dose-response relationship, and response to topical minoxidil were assessed using standardized clinical photographs of the scalp, trichoscopic images, and radiotherapy treatment plans. RESULTS: Of the 71 patients included (median [range] age, 27 [4-75] years; 51 female [72%]), 64 (90%) had a CNS tumor and 7 (10%) had head and neck sarcoma. Alopecia severity was grade 1 in 40 of 70 patients (56%), with localized (29 of 54 [54%]), diffuse (13 of 54 [24%]), or mixed (12 of 54 [22%]) patterns. The median (range) estimated scalp radiation dose was 39.6 (15.1-50.0) Gy; higher dose (odds ratio [OR], 1.15; 95% CI, 1.04-1.28) and proton irradiation (OR, 5.7; 95% CI, 1.05-30.8) were associated with greater alopecia severity (P < .001), and the dose at which 50% of patients were estimated to have severe (grade 2) alopecia was 36.1 Gy (95% CI, 33.7-39.6 Gy). Predominant trichoscopic features included white patches (16 of 28 [57%]); in 15 patients, hair-shaft caliber negatively correlated with scalp dose (correlation coefficient, −0.624; P = .01). The association between hair density and scalp radiation dose was not statistically significant (−0.381; P = .16). Twenty-eight of 34 patients (82%) responded to topical minoxidil, 5% (median follow-up, 61 [interquartile range, 21-105] weeks); 4 of 25 (16%) topical minoxidil recipients with clinical images improved in severity grade. Two patients responded to hair transplantation and 1 patient responded to plastic surgical reconstruction. CONCLUSIONS AND RELEVANCE: Persistent radiation-induced alopecia among patients with primary CNS tumors or head and neck sarcomas represents a dose-dependent phenomenon that has distinctive clinical and trichoscopic features. The findings of this study suggest that topical minoxidil and procedural interventions may have benefit in the treatment of pRIA.

Tall oil fatty acids (TOFA) are a byproduct from the Kraft pulping process, and they represent a renewable and inexpensive alternative with high potential as a renewable feedstock. Epoxidized TOFA have great potential as chemical intermediates. Epoxidation of oleic acid, TOFA, and distilled tall oil (DTO) was conducted in an isothermal batch reactor with in situ-formed peracetic acid using hydrogen peroxide as the reactant and acetic acid as the reaction carrier. Amberlite IR-120 was used as the solid heterogeneous catalyst. The catalyst loading effect, the reactant ratios, the reaction temperature (40–70 °C), and the influence of microwave irradiation on epoxidation and ring opening were studied. The application of microwave irradiation resulted in an improvement of the epoxidation rate in the absence of the catalyst. Lower product yields were obtained for the epoxidation of DTO than for TOFA because of the higher viscosity and high content of rosin acids which presumably promoted ring opening reactions. At higher temperatures, the selectivity to oxirane decayed due to ring opening. Titration analysis and NMR analysis confirmed that microwave irradiation induces the ring opening reactions for TOFA epoxidation, and it accelerates this process for DTO. The rapid nature of the microwave heating might have unchained a series of ring opening reactions between neighboring oxirane groups and with the nucleophilic agents in the reaction mixture.

The mechanisms leading to aggregation of the crystallin proteins of the eye lens remain largely unknown. We use atomistic multiscale molecular simulations to model the solution-state conformational dynamics of γD-crystallin and its cataract-related W42R variant at both infinite dilution and physiologically relevant concentrations. We find that the W42R variant assumes a distinct conformation in solution that leaves the Greek key domains of the native fold largely unaltered but lacks the hydrophobic interdomain interface that is key to the stability of wild-type γD-crystallin. At physiologically relevant concentrations, exposed hydrophobic regions in this alternative conformation become primary sites for enhanced interprotein interactions leading to large-scale aggregation.

Available experimental techniques cannot determine high-resolution three-dimensional structures of membrane proteins under a transmembrane voltage. Hence, the mechanism by which voltage-gated cation channels couple conformational changes within the four voltage sensor domains, in response to either depolarizing or polarizing transmembrane voltages, to opening or closing of the pore domain's ion channel remains unresolved. Single-membrane specimens, composed of a phospholipid bilayer containing a vectorially oriented voltage-gated K+channel protein at high in-plane density tethered to the surface of an inorganic multilayer substrate, were developed to allow the application of transmembrane voltages in an electrochemical cell. Time-resolved neutron reflectivity experiments, enhanced by interferometry enabled by the multilayer substrate, were employed to provide directly the low-resolution profile structures of the membrane containing the vectorially oriented voltage-gated K+channel for the activated, open and deactivated, closed states of the channel under depolarizing and hyperpolarizing transmembrane voltages applied cyclically. The profile structures of these single membranes were dominated by the voltage-gated K+channel protein because of the high in-plane density. Importantly, the use of neutrons allowed the determination of the voltage-dependent changes in both the profile structure of the membrane and the distribution of water within the profile structure. These two key experimental results were then compared to those predicted by three computational modeling approaches for the activated, open and deactivated, closed states of three different voltage-gated K+channels in hydrated phospholipid bilayer membrane environments. Of the three modeling approaches investigated, only one state-of-the-art molecular dynamics simulation that directly predicted the response of a voltage-gated K+channel within a phospholipid bilayer membrane to applied transmembrane voltages by utilizing very long trajectories was found to be in agreement with the two key experimental results provided by the time-resolved neutron interferometry experiments.