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Abstract Anti‐amyloidogenic properties of plant pigments betalains as potential nutraceuticals against Alzheimer's disease have been screened using 24 pure molecules. Twenty‐two betalains reduced amyloid aggregation in vitro, eight of them up to 100%, with IC50 values in the micromolar range. Atomic force and transmission electron microscopy images showed the typical fibrils associated with Alzheimer's disease and how betalains avoid its formation. Neuroprotection after ingestion was supported by in vivo experiments with Caenorhabditis elegans. Indoline‐betacyanin was the most effective molecule by significantly improving the chemotactic behavior of the CL2355 strain, a model of Alzheimer's disease. Furthermore, in‐depth molecular docking analyses revealed that the pigments interact with the N‐terminal region of the amyloid peptide. This work is the most comprehensive study in the field and provides in vitro, in vivo, and in silico evidence for the use of betalains as nutraceuticals of relevance in the prevention of Alzheimer's disease.

Abstract Selenium is an essential micronutrient for ruminants, which participates in the optimal functioning of proteins and enzymes that can combat oxidative stress in the body; however, its toxicity is documented in different species. The objective of this work was to describe macroscopic and microscopic lesions in lambs intoxicated with selenium administered through intraruminal boluses. The main lesions at necropsy were pulmonary oedema; the myocardial surface presented multifocal pale areas; the thyroid and thymus glands were decreased in size, and areas of necrosis, haemorrhage and hyperkeratosis were observed in the reticulum and rumen. At the microscopic level, congestion, haemorrhage, oedema and hyaline membranes were observed in the lung; hepatic congestion, haemorrhage, degeneration and necrosis; degeneration and necrosis of the reticulum mucosa, as well as areas of hyperplasia and hyperkeratosis; myocardial degeneration, necrosis and fibrosis; congestion, haemorrhage, degeneration and renal tubular necrosis; thyroid follicular atrophy and thymic cortical atrophy. This study evidenced the main lesions related to selenium poisoning in lambs supplemented with the mineral through intraruminal boluses.

Abstract Aims The objective of this study was to perform a cost–benefit analysis of the CardioMEMS HF System (Abbott Laboratories, Abbott Park, IL, USA) in a heart failure (HF) clinic in Spain by evaluating the real‐time remote monitoring of pulmonary artery pressures, which has been shown to reduce HF‐related hospitalizations and improve the quality of life for selected HF patients. Particularly, the study aimed to determine the value of CardioMEMS in Southern Europe, where healthcare costs are significantly lower and its effectiveness remains uncertain. Methods and results This single‐centre study enrolled all consecutive HF patients (N = 43) who had been implanted with a pulmonary artery pressure sensor (CardioMEMS HF System); 48.8% were females, aged 75.5 ± 7.0 years, with both reduced and preserved left ventricular ejection fraction; 67.4% of them were in New York Heart Association Class III. The number of HF hospitalizations in the year before and the year after the sensor implantation was compared. Quality‐adjusted life years gained based on a literature review of previous studies were calculated. The rate of HF hospitalizations was significantly lower at 1 year compared with the year before CardioMEMS implantation (0.25 vs. 1.10 events/patient‐year, hazard ratio 0.22, P = 0.001). At the end of the first year, the usual management outperformed the CardioMEMS HF System. By the end of the second year, the CardioMEMS system is estimated to reduce costs compared with usual management (net benefits of €346). Conclusions Based on the results, we suggest that remote monitoring of pulmonary artery pressure with the CardioMEMS HF System represents a midterm and long‐term efficient strategy in a healthcare setting in Southern Europe.

Abstract Terrestrial groundwater travels through subterranean estuaries before reaching the sea. Groundwater‐derived nutrients drive coastal water quality, primary production, and eutrophication. We determined how dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP), and dissolved organic nitrogen (DON) are transformed within subterranean estuaries and estimated submarine groundwater discharge (SGD) nutrient loads compiling > 10,000 groundwater samples from 216 sites worldwide. Nutrients exhibited complex, nonconservative behavior in subterranean estuaries. Fresh groundwater DIN and DIP are usually produced, and DON is consumed during transport. Median total SGD (saline and fresh) fluxes globally were 5.4, 2.6, and 0.18 Tmol yr−1 for DIN, DON, and DIP, respectively. Despite large natural variability, total SGD fluxes likely exceed global riverine nutrient export. Fresh SGD is a small source of new nutrients, but saline SGD is an important source of mostly recycled nutrients. Nutrients exported via SGD via subterranean estuaries are critical to coastal biogeochemistry and a significant nutrient source to the oceans.

Abstract Modern humans widely shaped present ecosystems through intentional and unintentional geographical redistribution of wildlife, both in historical and pre‐historical times. However, the patterns of ancient human‐mediated indirect changes in wildlife range are largely unknown, and the mechanisms behind them remain obscure. We used a multidisciplinary approach to (a) reconstruct the process of colonization of the Mediterranean Basin by a long‐lived bird of prey, the Bonelli's eagle (Aquila fasciata), and (b) test the hypothesis that this colonization was unintentionally favoured by anatomically modern humans through a release of competition by dominant species, primarily golden eagles (A. chrysaetos). The fossil record of Bonelli's eagles in the Mediterranean Basin was restricted to the last c. 50 ky. This timing matches the period of modern human presence in Europe. Distribution modelling showed that Bonelli's eagles find more suitable conditions in interglacial periods, while glacial maxima are largely unfavourable unless in coastal refugia. In agreement with this, all Bonelli's eagle's fossils were found in coastal areas, and demographic inference from genetic data revealed a drop in the effective population size by around the last glacial maximum. In today's communities, we found a strongly asymmetric competitive relationship between (subordinate) Bonelli's and (dominant) golden eagles, with the former occupying far more humanized areas than the latter both at the landscape scale and the local (i.e. nesting cliff) scale. Moreover, the nesting habitat overlap analysis indicated that, in the absence of the other species, a notably higher population of Bonelli's eagle, but not of golden eagle, could be expected. Our findings are consistent with the human‐mediated competitor release hypothesis, by which anatomically modern humans could have unintentionally favoured the large‐scale colonization by Bonelli's eagles of a previously competitively hostile Mediterranean Basin. Reconstructing the role of ancient humans in shaping present ecosystems may help to understand the historical, current and future population trajectories of competing species of conservation concern under the ongoing scenario of global environmental change. It also illustrates how human‐mediated apparent competition may promote large‐scale redistribution and colonization of wildlife, including long‐lived species. Read the free Plain Language Summary for this article on the Journal blog.

Abstract We present the case of a 26‐year‐old female with chronic urticaria (CU) with systemic symptoms in whom comprehensive laboratory and imaging studies led to the diagnosis of idiopathic multicentric Castleman disease. Treatment with rituximab induced resolution of CU. The association between these two entities is rare, and common autoimmune and autoinflammatory pathways may be involved in their production. Our case also emphasized the association of CU with an underlying systemic disease.

Abstract Aims Hypertonic saline solution (HSS) plus intravenous (IV) loop diuretic appears to enhance the diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this therapy in the ambulatory setting have not been evaluated. We aimed to describe the design and baseline characteristics of the SALT‐HF trial participants. Methods and results ‘Efficacy of Saline Hypertonic Therapy in Ambulatory Patients with HF’ (SALT‐HF) trial was a multicenter, double‐blinded, and randomized study involving ambulatory patients who experienced worsening heart failure (WHF) without criteria for hospitalization. Enrolled patients had to present at least two signs of volume overload, use ≥ 80 mg of oral furosemide daily, and have elevated natriuretic peptides. Patients were randomized 1:1 to treatment with a 1‐h infusion of IV furosemide plus HSS (2.6–3.4% NaCl depending on plasmatic sodium levels) versus a 1‐h infusion of IV furosemide at the same dose (125–250 mg, depending on basal loop diuretic dose). Clinical, laboratory, and imaging parameters were collected at baseline and after 7 days, and a telephone visit was planned after 30 days. The primary endpoint was 3‐h diuresis after treatment started. Secondary endpoints included (a) 7‐day changes in congestion data, (b) 7‐day changes in kidney function and electrolytes, (c) 30‐day clinical events (need of IV diuretic, HF hospitalization, cardiovascular mortality, all‐cause mortality or HF‐hospitalization). Results A total of 167 participants [median age, 81 years; interquartile range (IQR), 73–87, 30.5% females] were randomized across 13 sites between December 2020 and March 2023. Half of the participants (n = 82) had an ejection fraction >50%. Most patients showed a high burden of comorbidities, with a median Charlson index of 3 (IQR: 2–4). Common co‐morbidities included diabetes mellitus (41%, n = 69), atrial fibrillation (80%, n = 134), and chronic kidney disease (64%, n = 107). Patients exhibited a poor functional NYHA class (69% presenting NYHA III) and several signs of congestion. The mean composite congestion score was 4.3 (standard deviation: 1.7). Ninety per cent of the patients (n = 151) presented oedema and jugular engorgement, and 71% (n = 118) showed lung B lines assessed by ultrasound. Median inferior vena cava diameter was 23 mm, (IQR: 21–25), and plasmatic levels of N‐terminal‐pro‐B‐type natriuretic peptide (NTproBNP) and antigen carbohydrate 125 (CA125) were increased (median NT‐proBNP 4969 pg/mL, IQR: 2508–9328; median CA125 46 U/L, IQR: 20–114). Conclusions SALT‐HF trial randomized 167 ambulatory patients with WHF and will determine whether an infusion of hypertonic saline therapy plus furosemide increases diuresis and improves decongestion compared to equivalent furosemide administration alone.

Abstract Gprasp1 and Gprasp2 encode proteins that control the stability and cellular trafficking of CXCR4, a master regulator of hematopoiesis whose dynamic regulation is required for appropriate trafficking of B‐cells in the germinal center (GC). Here, we report that Gprasp1 and Gprasp2‐deficient B‐cells accumulate in the GC and show transcriptional abnormalities, affecting the mechanisms controlling Aicda expression and exposing them to excessive somatic hypermutation. Consequently, about 30% of mice transplanted with Gprasp‐deficient hematopoietic stem and progenitor cells developed a biologically aggressive and fatal B‐cell hyperproliferative disease by 20–50 weeks posttransplant. Histological and molecular profiling reveal that Gprasp1‐ and Gprasp2‐deficient neoplasms morphologically resemble human high‐grade B‐cell lymphomas of germinal center origin with shared morphologic features of both Burkitt Lymphoma (BL) and diffuse large B‐cell lymphoma (DLBCL), and molecular features consistent with DLBCL, as well as elevated mutational burden and heterogenous transcriptional and mutational signature. Thus, reduced Gprasp1 and Gprasp2 gene expression perturbs B‐cell maturation and increases the risk of B‐cell neoplasms of germinal center origin. As this model recapitulates the essential features of the heterogenous group of human hematopoietic malignancies, it could be a powerful tool to interrogate the mechanisms of lymphomagenesis for these cancers.

Abstract Metal‐free, luminescent, carbogenic nanomaterials (LCNMs) constitute a novel class of optical materials with low environmental impact. LCNMs, e.g., carbon dots (CDs), graphitic carbon nitride (g‐C3N4), and carbonized polymer microspheres (CPM) show strong blue/cyan emissions, but rather weak yellow/red emission. This has been a serious drawback in applying them to light‐emitting and bio‐imaging applications. Here, by integrating single‐component LCNMs in photonic microcavities, the study spectroscopically engineers the coupling between photonic modes in these microcavities and optical transitions to “reconfigure” the emission spectra of these luminescent materials. Resonant photons are confined in the microcavity, which allows selective re‐excitation of phosphors to effectively emit down‐converted photons. The down‐converted photons re‐excite the phosphors and are multiply recycled, leading to enhanced yellow/red emissions and resulting in white‐light emission (WLE). Furthermore, by adjusting photonic stop bands of microcavity components, color adaptable (cool, pure, and warm) WLE is flexibly generated, which precisely follows the black‐body Planckian locus in the chromaticity diagram. The proposed approach offers practical low‐cost chromaticity‐adjustable WLE from single‐component, luminescent materials without any chemical or surface modification, or elaborate machinery and processing, paving the way for practical WLE devices.

Abstract The European Commission (EC) asked EFSA to assess the genotoxicity of beauvericin (BEA). Relevant information, including that which has become available since the 2014 Scientific Opinion on the risks to human and animal health related to the presence of BEA and enniatins in food and feed, was reviewed. In the previous Opinion the Panel concluded that in vitro genotoxicity data were equivocal and there were no in vivo genotoxicity data available. New in vitro studies in mammalian cell lines provided no convincing evidence for induction of chromosomal damage by BEA as measured by micronucleus and chromosome aberration tests or an increase of DNA strand breaks as assessed by the Comet assay. In these studies, no concentration‐dependent effects or potential for interference from associated cytotoxicity were observed. In addition, DNA double‐strand breaks as measured by γ‐H2AX analysis were only observed following exposure to highly cytotoxic BEA concentrations. In vivo studies (Comet and Pig‐a assays, micronucleus test) with BEA were negative. In vitro gene expression studies showed no indication of a DNA damage response and (quantitative) structure activity relationship analysis was also not indicative of genotoxic potential. Some effects of BEA might play an indirect role in the formation of DNA strand breaks. These include increased reactive oxygen species, induction of cell cycle arrest and apoptosis, associated with interference in mitochondrial function and cell signalling. There was no compelling evidence of inflammatory and immunosuppressive effects. Taken together, the available data indicate that BEA is devoid of genotoxic potential.

Abstract The European Commission asked EFSA to update its 2012 risk assessment on brominated phenols and their derivatives in food, focusing on five bromophenols and one derivative: 2,4,6‐tribromophenol (2,4,6‐TBP), 2,4‐dibromophenol (2,4‐DBP), 4‐bromophenol (4‐BP), 2,6‐dibromophenol (2,6‐DBP), tetrabrominated bisphenol S (TBBPS), tetrabromobisphenol S bismethyl ether (TBBPS‐BME). Based on the overall evidence, the CONTAM Panel considered in vivo genotoxicity of 2,4,6‐TBP to be unlikely. Effects in liver and kidney were considered as the critical effects of 2,4,6‐tribromophenol (2,4,6‐TBP) in studies in rats. A BMDL10 of 353 mg/kg body weight (bw) per day for kidney papillary necrosis in male rats was identified and was selected as the reference point for the risk characterisation. The derivation of a health‐based guidance value was not considered appropriate due to major limitations in the toxicological database. Instead, the margin of exposure (MOE) approach was applied to assess possible health concerns. Around 78,200 analytical results for 2,4,6‐TBP in food were used to estimate dietary exposure for the European population. Considering the resulting MOE values, all far above an MOE of 6000 that does not raise a health concern, and accounting for the uncertainties affecting the exposure and hazard assessments, the CONTAM Panel concluded with at least 95% probability that the current dietary exposure to 2,4,6‐TBP does not raise a health concern. Due to lack of occurrence data, no risk assessment could be performed for breastfed or formula‐fed infants. No risk characterisation could be performed for any of the other brominated phenols and derivatives included in the assessment, due to lack of data both on the toxicity and occurrence.

ABSTRACT Aim To implement shared decision‐making (SDM) through a patient decision aid (PtDA) for the initiation of palliative care (PC) in end‐of‐life (EOL) cancer patients. Methodology A comprehensive Scoping Review was conducted on SDM in PubMed, CINAHL and PsycInfo. An evidence‐based implementation of PtDAs was created using the Joanna Briggs Institute framework, which followed rigorous pillars: (1) context, (2) facilitation and (3) evaluation. Results Fifteen studies were identified and categorised into (1) Implementation characteristics and (2) Strategies for implementing SDM in terminally ill cancer patients. SDM should consider the decision‐making location, optimal timing, participants and decision type. Strategies include professional training, PtDAs and implementation programmes. A PtDA implementation protocol in video format for deciding to initiate PC is proposed, following International Patient Decision Aid Standards (IPDAS) and Clinical Practice Guidelines (CPG). Conclusions SDM implementation should be guided by evidence‐based methodological models justifying and structuring its execution, especially in complex and interdisciplinary contexts. National or international frameworks facilitate the adoption of health innovations, such as PtDAs, benefiting patients and improving their usage. Practice Implications SDM is not just a concept but an important approach to the Care of cancer patients at EOL, enhancing patient satisfaction and improving care quality. The success and sustainability of SDM hinge on the fundamental aspects of staff training, interdisciplinary collaboration and ongoing evaluation. The lack of specific aid in Spanish underscores the immediate need for local development. Further research is needed in this area, as most reviewed studies did not measure SDM effectiveness in diverse hospital settings. Patient or Public Contribution This proposal was developed based on the experience and input of the nursing staff from the healthcare service where it is intended to be implemented.

Abstract Background Structural income inequality – the uneven income distribution across regions or countries – could affect brain structure and function, beyond individual differences. However, the impact of structural income inequality on the brain dynamics and the roles of demographics and cognition in these associations remains unexplored. Methods Here, we assessed the impact of structural income inequality, as measured by the Gini coefficient on multiple EEG metrics, while considering the subject‐level effects of demographic (age, sex, education) and cognitive factors. Resting‐state EEG signals were collected from a diverse sample (countries = 10; healthy individuals = 1394 from Argentina, Brazil, Colombia, Chile, Cuba, Greece, Ireland, Italy, Turkey and United Kingdom). Complexity (fractal dimension, permutation entropy, Wiener entropy, spectral structure variability), power spectral and aperiodic components (1/f slope, knee, offset), as well as graph‐theoretic measures were analysed. Findings Despite variability in samples, data collection methods, and EEG acquisition parameters, structural inequality systematically predicted electrophysiological brain dynamics, proving to be a more crucial determinant of brain dynamics than individual‐level factors. Complexity and aperiodic activity metrics captured better the effects of structural inequality on brain function. Following inequality, age and cognition emerged as the most influential predictors. The overall results provided convergent multimodal metrics of biologic embedding of structural income inequality characterised by less complex signals, increased random asynchronous neural activity, and reduced alpha and beta power, particularly over temporoposterior regions. Conclusion These findings might challenge conventional neuroscience approaches that tend to overemphasise the influence of individual‐level factors, while neglecting structural factors. Results pave the way for neuroscience‐informed public policies aimed at tackling structural inequalities in diverse populations.

Abstract Droplet‐based bioprinting has shown remarkable potential in tissue engineering and regenerative medicine. However, it requires bioinks with low viscosities, which makes it challenging to create complex 3D structures and spatially pattern them with different materials. This study introduces a novel approach to bioprinting sophisticated volumetric objects by merging droplet‐based bioprinting and cryobioprinting techniques. By leveraging the benefits of cryopreservation, we fabricated, for the first time, intricate, self‐supporting cell‐free or cell‐laden structures with single or multiple materials in a simple droplet‐based bioprinting process that is facilitated by depositing the droplets onto a cryoplate followed by crosslinking during revival. The feasibility of this approach is demonstrated by bioprinting several cell types, with cell viability increasing to 80%–90% after up to 2 or 3 weeks of culture. Furthermore, the applicational capabilities of this approach are showcased by bioprinting an endothelialized breast cancer model. The results indicate that merging droplet and cryogenic bioprinting complements current droplet‐based bioprinting techniques and opens new avenues for the fabrication of volumetric objects with enhanced complexity and functionality, presenting exciting potential for biomedical applications.

Abstract The genus Eutreptiella (Euglenophyceae/Euglenozoa) comprises unicellular organisms known for their photosynthetic capacity and significant role in marine ecosystems. This review highlights the taxonomic, ecological, and biotechnological characteristics of Eutreptiella species, emphasizing their morphological and genomic adaptations. Eutreptiella species exhibit high phenotypic plasticity, enabling adaptation to various environmental conditions, from nutrient‐rich waters to high‐salinity conditions. They play a crucial role in primary production and nutrient cycling in marine ecosystems. Genetic and transcriptomic studies have revealed their complex regulatory mechanisms and potential for biofuel and nutraceutical production. Eutreptiella blooms significantly impact local ecosystems, influencing nutrient availability and community dynamics. Additionally, interactions with associated bacteria enhance their growth and metabolic capabilities. The genus shows substantial genetic variability, suggesting potential misidentifications or a polyphyletic nature. Further comprehensive studies are needed to clarify their taxonomy and evolutionary relationships. Understanding and managing Eutreptiella populations is essential to leverage their biotechnological potential and ensure the health of marine ecosystems.

Abstract The challenges of the modern world require mobile robots with the ability to navigate in congested environments with high levels of manoeuvrability. Therefore, the Mecanum wheel may be viable for addressing this challenge. This paper presents the experimental results of a kinematic control strategy, which involves considering the dynamic model as a black box, with only the input and output signals being known. To do this, high‐level and low‐level controllers are formulated and explained. The high level aims to control the desired position of the mobile robot, which can be useful for navigation tasks. On the other hand, low‐level control involves nested controllers to regulate the speed of the mobile robot wheels. Both levels are related and computed through pure kinematics transformations with a dSPACE ds1103 card and MATLAB/Simulink software. In total, 120 experiments were conducted to determine the repeatability of the tests, using the combination of three widely explored control techniques in the literature: proportional‐integral‐derivative (PID), PID plus sliding modes, and PID plus quasi‐sliding modes. The experiments conducted are described in detail, and the results are analysed using statistical indices based on the RMS error and percentage improvement.

Key Clinical Message Several electrocardiographic alterations due to hypokalemia have been described, but the electrocardiographic presentation meeting criteria for occlusion of the left main coronary artery is very rare. We describe a case of hypokalemia simulating it.

Abstract Increased circulating tissue inhibitor of metalloproteinases‐1 (TIMP‐1) levels have been observed in patients with acute lung injury (ALI). However, the sex‐specific regulation of TIMP‐1 and the underlying molecular mechanisms have not been well elucidated. In this study, we found that plasma TIMP‐1 levels were significantly higher in COVID‐19 and H1N1 patients compared with those in healthy subjects (n = 25). TIMP‐1 concentrations were significantly different between males and females in each disease group. Among female but not male patients, TIMP‐1 levels significantly correlated with the PaO2/FiO2 ratio and hospital length of stay. Using the mouse model of ALI induced by the H1N1 virus, we found that TIMP‐1 is strikingly induced in PDGFRα‐positive cells in the murine lungs. Moreover, female mice showed a higher Timp‐1 expression in the lungs on day 3 postinfection. Mechanistically, we observed that estrogen can upregulate TIMP‐1 expression in lung fibroblasts, not epithelial cells. In addition, overexpression of estrogen receptor α (ERα) increased the TIMP‐1 promoter activity. In summary, TIMP‐1 is an estrogen‐responsive gene, and its promoter activity is regulated by ERα. Circulating TIMP‐1 may serve as a sex‐specific marker, reflecting the severity and worst outcomes in female patients with SARS‐CoV2‐ and IAV‐related ALI.

Abstract Palaeocurrent analysis is vital for basin analysis and helps in the interpretation of depositional environments (along‐slope or downslope). For that, it is crucial to have multiple measuring methods at hand to apply palaeocurrent analysis with a wide range of different datasets (outcrops, cores and photographs). Here, two relatively underexploited palaeocurrent measurement techniques are assessed when applied to trough cross‐stratification observed in the Arenazzolo Formation at Eraclea Minoa (Sicily). The first technique is a novel design of a qualitative approach to infer palaeocurrent directions from photographs of two‐dimensional sedimentary structures. The second technique involves measurements of the anisotropy of magnetic susceptibility from drilled samples. A broad agreement, with overlapping uncertainty boundaries, is observed between results from both techniques. This agreement validates the use of trough cross‐strata to infer palaeocurrent directions. Moreover, the addition of photographs improves reproducibility and prevents a bias towards the best‐exposed troughs. The application of both techniques to outcrops and sedimentary cores provides new opportunities for palaeocurrent analysis in any type of sedimentary environment.

The initial excitement generated more than two decades ago by the discovery of drugs targeting fatty acid synthase (FASN)‐catalyzed de novo lipogenesis for cancer therapy was short‐lived. However, the advent of the first clinical‐grade FASN inhibitor (TVB‐2640; denifanstat), which is currently being studied in various phase II trials, and the exciting advances in understanding the FASN signalome are fueling a renewed interest in FASN‐targeted strategies for the treatment and prevention of cancer. Here, we provide a detailed overview of how FASN can drive phenotypic plasticity and cell fate decisions, mitochondrial regulation of cell death, immune escape and organ‐specific metastatic potential. We then present a variety of FASN‐targeted therapeutic approaches that address the major challenges facing FASN therapy. These include limitations of current FASN inhibitors and the lack of precision tools to maximize the therapeutic potential of FASN inhibitors in the clinic. Rethinking the role of FASN as a signal transducer in cancer pathogenesis may provide molecularly driven strategies to optimize FASN as a long‐awaited target for cancer therapeutics.

Abstract Background Prurigo nodularis (PN) is a chronic, debilitating dermatologic disease characterised by the presence of highly pruritic nodular lesions. PN highly impacts on patients' quality of life as there are no specific treatments available in Spain. Objectives Determine the main value drivers in the treatment of PN in Spain and its main unmet needs using Multi‐Criteria Decision Analysis (MCDA). Methods Literature review to synthesise relevant evidence in an evidence matrix based on the MCDA EVIDEM framework adapted to Spain. A multidisciplinary panel composed of dermatologists, hospital pharmacists and a patient weighted (5‐point scale; 0 minimum importance, 5 maximum importance) and scored each criterion included in the framework (from −5 to 5 or 0 to 5 depending on the criterion). Results were discussed in a reflective group session. Results PN was considered a severe (3.3 ± 0.7) and infrequent (2.0 ± 0.7) disease, with high unmet needs (4.2 ± 0.7) mainly due to the lack of available treatments with specific indication for PN. Current off‐label treatments were perceived to have limited efficacy/effectiveness (1.8 ± 1.1), an unfavourable long‐term safety profile (2.1 ± 0.9) and low therapeutic impact (1.7 ± 1.1). The measure of patient‐reported outcomes (2.7 ± 0.9) was perceived as important, but available tools are not specific. Although the cost of available treatments was not considered high (2.4 ± 1.5), experts agreed that PN is associated with moderately high other medical costs (3.6 ± 1.1) and indirect costs (3.1 ± 0.9). Experts considered that current guidelines and consensus (2.6 ± 0.7) are not clear on severity criteria and treatment algorithm. The quality of evidence (1.4 ± 0.5) of currently used off‐label treatments was perceived as low due to a lack of published clinical trials. Conclusions PN was considered a severe disease associated with relevant unmet needs, including the lack of specific and effective treatments for PN, the lack of consensus on the disease definition, defined severity criteria, prevalence estimations and awareness of PN in Spain.

Abstract The adverse outcome pathway (AOP) framework serves as a practical tool for organising scientific knowledge that can be used to infer cause–effect relationships between stressor events and toxicity outcomes in intact organisms. However, a major challenge in the broader application of the AOP concept within regulatory toxicology is the development of a robust AOPs that can withstand peer review and acceptance. This is mainly due to the considerable amount of work required to substantiate the modular units of a complete AOP, which can take years from inception to completion. The methodology used here consisted of an initial assessment of a single chemical hazard using the Integrated Approach to Testing and Assessment (IATA) framework. An evidence‐based approach was then used to gather empirical evidence combining systematic literature review methods with expert knowledge to ensure the effectiveness of the AOP development methodology. The structured framework used assured transparency, objectivity and comprehensiveness, and included expert knowledge elicitation for the evaluation of key event relationships (KERs). This stepwise approach led to the development of an AOP that begins with binding of chemicals to Voltage Gate Sodium Channels (VGSC/Nav) during mammalian development leading to adverse consequences in neurodevelopment evidenced as deficits in cognitive functions. Disruption of the formation of precise neural circuits by alterations in VGSC kinetics during the perinatal stages of brain development may also underlie neurodevelopmental disorders. Gaps in our understanding include the specific critical developmental windows and the quantitative relationship of binding to VGSC and subsequent disruption and cognitive function. Despite the limited quantitative information at all KER levels, regulatory applications of this AOP for DNT assessment have been identified.

Abstract It is accepted that loliginids, like other squid, deposit their eggs in crevices on the seabed and then abandon them. In this work, we present observational evidence of egg guarding behavior in wild European squid, Loligo vulgaris. While monitoring a squid spawning crevice at night in Spain, a large mass of squid eggs was located and filmed 17 times during 42 days, until hatching. A male and a female of L. vulgaris were filmed in front of the crevice. The same male was filmed guarding the eggs on consecutive days. In the presence of the divers, male and female alternated their approaches to the crevice repeatedly touching and flushing the egg clusters. This guarding behavior differs from the reproductive habits assumed for the European squid and could represent the first evidence of egg guarding by a male in cephalopods.

Abstract The 22‐hydroxy‐23,24‐bisnorchol‐4‐ene‐3‐one (4‐HBC) is a C22 steroid synthon of pharmaceutical interest that can be produced as a lateral end‐product of the catabolism of natural sterols (e.g., cholesterol or phytosterols). This work studies the role of an aldehyde dehydrogenase coded by the MSMEG_6563 gene of Mycolicibacterium smegmatis, named msRed, in 4‐HBC production. This gene is located contiguously to the MSMEG_6561 encoding the aldolase msSal which catalyses the retroaldol elimination of acetyl‐CoA of the metabolite intermediate 22‐hydroxy‐3‐oxo‐cholest‐4‐ene‐24‐carboxyl‐CoA to deliver 3‐oxo‐4‐pregnene‐20‐carboxyl aldehyde (3‐OPA). We have demonstrated that msRed reduces 3‐OPA to 4‐HBC. Moreover, the role of msOpccR reductase encoded by MSMEG_1623 was also explored confirming that it also performs the reduction of 3‐OPA into 4‐HBC, but less efficiently than msRed. To obtain a M. smegmatis 4‐HBC producer strain we deleted MSMEG_5903 (hsd4A) gene in strain MS6039‐5941 (ΔkshB1, ΔkstD1) that produces 4‐androstene‐3,17‐dione (AD) from natural sterols (cholesterol or phytosterols). The triple MS6039‐5941‐5903 mutant was able to produce 9 g/L of 4‐HBC from 14 g/L of phytosterols in 2 L bioreactor, showing a productivity of 0.140 g/L h−1. To improve the metabolic flux of sterols towards the production of 4‐HBC we have cloned and overexpressed the msSal and msRed enzymes in the MS6039‐5941‐5903 mutant rendering a production titter of 12.7 g/L with a productivity of 0.185 g/L h−1, and demonstrating that the new recombinant strain has a great potential for its industrial application.

Abstract The EFSA Scientific Committee has updated its 2010 Guidance on risk–benefit assessment (RBA) of foods. The update addresses methodological developments and regulatory needs. While it retains the stepwise RBA approach, it provides additional methods for complex assessments, such as multiple chemical hazards and all relevant health effects impacting different population subgroups. The updated guidance includes approaches for systematic identification, prioritisation and selection of hazardous and beneficial food components. It also offers updates relevant to characterising adverse and beneficial effects, such as measures of effect size and dose–response modelling. The guidance expands options for characterising risks and benefits, incorporating variability, uncertainty, severity categorisation and ranking of different (beneficial or adverse) effects. The impact of different types of health effects is assessed qualitatively or quantitatively, depending on the problem formulation, scope of the RBA question and data availability. The integration of risks and benefits often involves value‐based judgements and should ideally be performed with the risk–benefit manager. Metrics such as Disability‐Adjusted Life Years (DALYs) and Quality‐Adjusted Life Years (QALYs) can be used. Additional approaches are presented, such as probability of all relevant effects and/or effects of given severities and their integration using severity weight functions. The update includes practical guidance on reporting results, interpreting outcomes and communicating the outcome of an RBA, considering consumer perspectives and responses to advice.

Abstract Bottom currents play a major role in deep‐sea sedimentation, but their significance in the burial of organic carbon is poorly quantified at a global scale. Here we show that Holocene fluxes of organic carbon into the contourite drifts are high, with a global average of 0.09 g cm−2 Kyr−1. At individual drift sites, fluxes are commonly 1–2 orders of magnitude greater than rates in surrounding areas and in global depth‐similar zones. These high fluxes of organic carbon into the contourite drifts are due to high rates of sedimentation. Over the past 50 million years, sedimentation rates at the studied contourite drift sites have overall increased, coincident with decreasing atmospheric CO2 and a cooling global climate. Our work suggests that a ramp‐up of the bottom‐current carbon pump has accelerated removal of CO2 from the atmosphere and oceanic water, thus contributing to the overall global cooling after the Eocene Thermal Maximum.

Abstract We document an apparent downward displacement of the Matuyama‐Brunhes magnetic reversal by ∼20 m at Scotia Sea International Ocean Discovery Program Site U1538 (Pirie Basin) by comparison with the well‐defined paleomagnetic record at nearby Site U1537 (Dove Basin). Detailed stratigraphic correlation between the two sites is possible due to similar lithologic variations. However, the two sites have distinctly different porewater geochemistry. Notably, Site U1538 indicates a greater demand for electron acceptors to oxidize organic carbon and Fe2+ enrichment below the depth of SO42− depletion. Magnetic parameters indicate enrichment of an authigenic magnetic mineral with strong remanence properties around the depth of SO42− depletion (∼46 m at Site U1538) relative to magnetic parameters at correlative depths at Site U1537. Fe2+ enrichment below the depth of SO42− depletion is not predicted based on the energetically favorable order of electron acceptors for microbial respiration but is documented here and in other depositional settings. This indicates Fe2+ production exceeds the production of H2S by SO42− reduction, providing a geochemical environment that favors the production and preservation of ferrimagnetic remanence‐bearing iron sulfides over paramagnetic pyrite and, thus, a mechanism for deep chemical remanent magnetization acquisition at depths of tens of meters. The influence of authigenic ferrimagnetic iron sulfides on paleomagnetic signals can be difficult to demonstrate with magnetic properties alone; therefore, this finding has implications for evaluating the fidelity of magnetostratigraphic records with complementary geochemical data. Such situations should be considered in other depositional environments with similar porewater Fe2+ accumulation below the SO42− reduction depth.

Abstract Multiple myeloma (MM) is a genetically heterogeneous disease and the management of relapses is one of the biggest clinical challenges. TP53 alterations are established high‐risk markers and are included in the current disease staging criteria. KRAS is the most frequently mutated gene affecting around 20% of MM patients. Applying Clonal Competition Assays (CCA) by co‐culturing color‐labeled genetically modified cell models, we recently showed that mono‐ and biallelic alterations in TP53 transmit a fitness advantage to the cells. Here, we report a similar dynamic for two mutations in KRAS (G12A and A146T), providing a biological rationale for the high frequency of KRAS and TP53 alterations at MM relapse. Resistance mutations, on the other hand, did not endow MM cells with a general fitness advantage but rather presented a disadvantage compared to the wild‐type. CUL4B KO and IKZF1 A152T transmit resistance against immunomodulatory agents, PSMB5 A20T to proteasome inhibition. However, MM cells harboring such lesions only outcompete the culture in the presence of the respective drug. To better prevent the selection of clones with the potential of inducing relapse, these results argue in favor of treatment‐free breaks or a switch of the drug class given as maintenance therapy. In summary, the fitness benefit of TP53 and KRAS mutations was not treatment‐related, unlike patient‐derived drug resistance alterations that may only induce an advantage under treatment. CCAs are suitable models for the study of clonal evolution and competitive (dis)advantages conveyed by a specific genetic lesion of interest, and their dependence on external factors such as the treatment.

Key Clinical Message The commonest renal involvement after bee stings is acute kidney injury due to rhabdomyolysis. Nephrotic syndrome combined with AKI is unusual complication of Hymenoptera stings. We diagnosed a minimal change disease and six‐year follow up relapses.

Abstract The biochemical pathway for propionic acid (PA) production is an interesting alternative that can include the utilization of biomass as feedstock. This study evaluated the utilization of Agave bagasse (AB), a lignocellulosic residue, to produce PA by Propionibacterium acidipropinici in batch systems (125 mL‐hermetic bottles and 1000 mL‐bioreactor). The process included a steam explosion pretreatment at 142°C for 15 min and enzymatic hydrolysis, where solid loading (2.75% and 5% in pretreatment and 2.5%, 3.75%, and 5% in enzymatic hydrolysis) was evaluated. Furthermore, the enzymatic concentrations of 18.3 filter paper unit (FPU)/gAB (1×) of Cellic® CTec2 and 1.5× and 3× were tested. The yields of total carbohydrates (TC) obtained at the two solid loadings tested in the pretreatment were statistically similar, but the 3x enzymatic concentration enhanced the yields of TC, glucose, and xylose (0.23 ± 0.01, 0.15 ± 0.01 and 0.03 ± 0.01 g/gAB, respectively). The hydrolysates obtained under these conditions were evaluated as carbon sources for PA production, obtaining a productivity of 0.069 ± 0.006 g/L h and a yield product/substrate of 0.44 gPA/gTC. The control of pH in the culture reduced the fermentation time in the bioreactor by 52% compared with the hermetic bottles without pH control. The potential of hydrolysates as carbon sources for PA production was evidenced, as approximately 50% of the initial carbon was converted to this product. The observed yield product/substrate was similar to those reported from hydrolysates of diverse biomass types, pretreatments, or enzymatic cocktails and the same or related microorganisms. However, the system studied has advantages, such as not requiring the addition of chemical or detoxification stage, and lower temperature and time compared to other pretreatments.

Abstract Bioethanol has been identified as a renewable product with high potential for application as biofuel. On the other hand, high volumes of agri‐food residues are generated daily. Such residues have potential as raw materials for industrial bioethanol production. There is a significant advance in the synthesis of biofuels from fruit and vegetable residues; however, most of the studies are focused on the conversion of a single type of raw material, limiting the application of the synthesis routes. This work presents a conversion methodology to produce bioethanol from carrot and broccoli residues and from their mixture; the samples of vegetable wastes has been collected in the municipality of Guanajuato, Mexico. Using the 1H NMR technique, the characteristic signals of bioethanol are identified. On the other hand, using the UV–VIS spectrophotometry technique, a maximum of 25.63 mg of total sugar content has been determined for the mixture. Likewise, a maximum bioethanol concentration of 60.6 g/L is obtained. From a refractometry and HPLC study, a conversion to bioethanol of 34.8% is determined for the mixture of residues. This work analyses the potential of broccoli and carrot residues for bioethanol production, either as isolated or as mixed wastes.

BACKGROUND Atherosclerosis is triggered by the retention of apolipoprotein B‐containing lipoproteins by proteoglycans. In addition to low‐density lipoprotein, remnant lipoproteins have emerged as pivotal contributors to this pathology, particularly in the context of insulin resistance and diabetes. We have previously reported antiatherogenic properties of a monoclonal antibody (chP3R99) that recognizes sulfated glycosaminoglycans on arterial proteoglycans. METHODS AND RESULTS Solid‐phase assays demonstrated that chP3R99 effectively blocked >50% lipoprotein binding to chondroitin sulfate and vascular extracellular matrix in vitro. The preperfusion of chP3R99 (competitive effect) resulted in specific antibody‐arterial accumulation and reduced fluorescent lipoprotein retention by ~60% in insulin resistant JCR:LA‐cp rats. This competitive reduction was dose dependent (25–250 μg/mL), effectively decreasing deposition of cholesterol associated with lipoproteins. In a 5‐week vaccination study in insulin resistant rats with (200 μg subcutaneously, once a week), chP3R99 reduced arterial lipoprotein retention, and was associated with the production of antichondroitin sulfate antibodies (Ab3) able to accumulate in the arteries (dot‐blot). Neither the intravenous inoculation of chP3R99 (4.5 mg/kg), nor the immunization with this antibody displayed adverse effects on lipid or glucose metabolism, insulin resistance, liver function, blood cell indices, or inflammation pathways in JCR:LA‐cp rats. CONCLUSIONS Both acute (passive) and long‐term administration (idiotypic cascade) of chP3R99 antibody reduced low‐density lipoprotein and remnant lipoprotein interaction with proteoglycans in an insulin‐resistant setting. These findings support the innovative approach of targeting proatherogenic lipoprotein retention by chP3R99 as a passive therapy or as an idiotypic vaccine for atherosclerosis.

Abstract Selecting and mating parents in conventional phenotypic and genomic selection are crucial. Plant breeding programs aim to improve the economic value of crops, considering multiple traits simultaneously. When traits are negatively correlated and/or when there are missing records in some traits, selection becomes more complex. To address this problem, we propose a multitrait selection approach using the Multitrait Parental Selection (MPS) R package—an efficient tool for genetic improvement, precision breeding, and conservation genetics. The package employs Bayesian optimization algorithms and three loss functions (Kullback–Leibler, Energy Score, and Multivariate Asymmetric Loss) to identify parental candidates with desirable traits. The software's functionality includes three main functions—EvalMPS, FastMPS, and ApproxMPS—catering to different data availability scenarios. Through the presented application examples, the MPS R package proves effective in multitrait genomic selection, enabling breeders to make informed decisions and achieve strong performance across multiple traits.

Abstract Background Leptospirosis is a zoonotic disease and a challenge to global public health. There is an occupational risk, particularly in populations with direct contact with animals and in high‐humidity environments, which favors the survival of leptospires. This study aimed to determine the seroprevalence of leptospirosis in military personnel working in close contact with animals in México and to describe the available preventive measures and protection levels. Methods A cross‐sectional study was conducted from March to October 2015. Information regarding protective factors in daily activities was gathered through a self‐evaluation questionnaire. The serum samples of participants were analyzed through enzyme‐linked immunoassay (ELISA) and microscopic agglutination test. Results Serums were obtained from 65 active military personnel, 56 males (86.2%) and 9 females (13.8%). Out of the total, 54 (83.1%) tested positive for infection by leptospirosis, 49 were males (87.5%) and 5 were females (55.6%). The highest seroprevalence age group was in the ≥45 years group (15, 23.07%), where all tested positive. Regarding military ranks, 100% of the highest hierarchy turned out positive: Officers (4 out of 4) and Chiefs (14 out of 14); and troops resulted in a seroprevalence of 76.5%. Protection equipment available during daily chores included: Overall, 64.6% had gloves and 53.8% had boots; the reported frequency for the use of gloves was 35.3% (46/65) if worn during more than half of the workday, yet 29.2% (19/65) reported never wearing them. Conclusions This study makes the petition to implement protocols of continuous training regarding labor risks and having an epidemiologic surveillance program for exposed personnel indispensable to improve the health and sanitary conditions of military personnel who work in direct contact with animals.

Abstract Bdellovibrio bacteriovorus HD100 is an obligate predatory bacterium that preys upon Gram‐negative bacteria. It has been proposed to be applied as a “living antibiotic” in several fields such as agriculture or even medicine, since it is able to prey upon bacterial pathogens. Its interesting lifestyle makes this bacterium very attractive as a microbial chassis for co‐culture systems including two partners. A limitation to this goal is the scarcity of suitable synthetic biology tools for predator domestication. To fill this gap, we have firstly adapted the hierarchical assembly cloning technique Golden Standard (GS) to make it compatible with B. bacteriovorus HD100. The chromosomal integration of the Tn7 transposon's mobile element, in conjunction with the application of the GS technique, has allowed the systematic characterization of a repertoire of constitutive and inducible promoters, facilitating the control of the expression of heterologous genes in this bacterium. PJExD/EliR proved to be an exceptional promoter/regulator system in B. bacteriovorus HD100 when precise regulation is essential, while the synthetic promoter PBG37 showed a constitutive high expression. These genetic tools represent a step forward in the conversion of B. bacteriovorus into an amenable strain for microbial biotechnology approaches.

Abstract Intraspecific variation in plants is expected to have profound impacts on the arthropod communities associated with them. Because sexual dimorphism in plants is expected to provide consistent variation among individuals of the same species, researchers have often studied the effect it has on associated arthropods. Nevertheless, most studies have focused on the effect of sexual dimorphism in a single or a few herbivores, thus overlooking the potential effects on the whole arthropod community. Our main objective was to evaluate effects of Buddleja cordata's plant‐sex on its associated arthropod community. We surveyed 13 pairs of male and female plants every 2 months during a year (June 2010 to April 2011). Every sampling date, we measured plant traits (water content and leaf thickness), herbivory, and the arthropod community. We did not find differences in herbivory between plant sex or through time. However, we found differences in water content through time, with leaf water‐content matching the environmental seasonality. For arthropod richness, we found 68 morphospecies associated with female and 72 with male plants, from which 53 were shared by both sexes. We did not observe differences in morphospecies richness; however, we found sex‐associated differences in the diversity of all species and differences on the diversity of the most abundant species with an interesting temporal component. During peak flowering season, male plants showed higher values on both parameters, but during the peak fructification season female plants showed the higher values on both diversity parameters. Our research exemplifies the interaction between plant‐phenology and plant‐sex as drivers of arthropod communities' diversity, even when plant sexual‐dimorphism is inconspicuous, and highlighting the importance of accounting for seasonal variation. We stress the need of conducting more studies that test this time‐dependent framework in other dioecious systems, as it has the potential to reconcile previous contrasting observations reported in the literature.

Abstract Chemoresistance is a common problem in ovarian cancer (OvCa) treatment, where resistant cells, in response to chemotherapy, secrete small extracellular vesicles (sEVs), known as chemo‐sEVs, that transfer resistance to recipient cells. sEVs are formed as intraluminal vesicles (ILVs) within multivesicular endosomes (MVEs), whose trafficking is regulated by Ras‐associated binding (RAB) GTPases that mediate sEVs secretion or lysosomal degradation. A decrease in lysosomal function can promote sEVs secretion, but the relationship between MVEs trafficking pathways and sEVs secretion in OvCa chemoresistance is unclear. Here, we show that A2780cis cisplatin (CCDP) resistant OvCa cells had an increased number of MVEs and ILVs structures, higher levels of Endosomal Sorting Complex Required for Transport (ESCRTs) machinery components, and RAB27A compared to A2780 CDDP‐sensitive OvCa cells. CDDP promoted the secretion of chemo‐sEVs in A2780cis cells, enriched in DNA damage response proteins. A2780cis cells exhibited poor lysosomal function with reduced levels of RAB7, essential in MVEs‐Lysosomal trafficking. The silencing of RAB27A in A2780cis cells prevents the Chemo‐EVs secretion, reduces its chemoresistance and restores lysosomal function and levels of RAB7, switching them into an A2780‐like cellular phenotype. Enhancing lysosomal function with rapamycin reduced chemo‐sEVs secretion. Our results suggest that adjusting the balance between secretory MVEs and lysosomal MVEs trafficking could be a promising strategy for overcoming CDDP chemoresistance in OvCa.

Abstract Bagging is an essential skill that humans perform in their daily activities. However, deformable objects, such as bags, are complex for robots to manipulate. A learning‐based framework that enables robots to learn bagging is presented. The novelty of this framework is its ability to learn and perform bagging without relying on simulations. The learning process is accomplished through a reinforcement learning (RL) algorithm introduced and designed to find the best grasping points of the bag based on a set of compact state representations. The framework utilises a set of primitive actions and represents the task in five states. In our experiments, the framework reached 60% and 80% success rates after around 3 h of training in the real world when starting the bagging task from folded and unfolded states, respectively. Finally, the authors test the trained RL model with eight more bags of different sizes to evaluate its generalisability.

Societal Impact Statement The human population is expected to reach 9.7 billion in the next 30 years, increasing the strain on our already precarious food system. Climate change is shifting weather patterns, leading to unpredictable and catastrophic events that further threaten the agronomic sector. Plant scientists are implementing biotechnological tools to sustainably increase both the production and nutritional content of our crops. Engineering GOLDEN2‐LIKE (GLK) transcription factors is a promising route to improve photosynthesis, as well as other important agronomical traits, to achieve food security for a growing population under an unpredictable climate. Summary Using agricultural biotechnology to increase the photosynthetic efficiency of crops has been a focus of plant science research over the last two decades. Transcription factors coordinate the expression of gene networks that are the basis of plant development and physiological responses and, as such, are good targets to help improve photosynthesis. Among the known plant transcriptional regulators, GOLDEN2‐LIKE transcription factors (GLKs) may be ideal candidates to improve photosynthesis in crops, as they are master regulators of genes associated with photosynthesis and chloroplast biogenesis across a broad diversity of plant lineages. Moreover, recent work has revealed their involvement in environmental response, pathogen defence and development regulation across the plant's whole life cycle. Thus, manipulating GLK expression and activity, alone or likely in combination with other modifications, has clear potential to improve plant development and growth. Here, we review the research into GLK function and discuss the potential of these key transcription factors as biotechnological tools to enhance photosynthetic efficiency and stress tolerance in crops. Additionally, we take advantage of the vast plant genome and transcriptome datasets available to explore the evolutionary history of GLKs across the plant kingdom and discuss the implications for their adoption into crop engineering projects.

Abstract Ocrelizumab (OCR) is a humanized anti‐CD20 monoclonal antibody approved for treating multiple sclerosis. We present three patients who developed psoriasiform dermatitis (PsD) during OCR treatment and a review of the cases published to date. We hereby report the first exclusive fingernail involvement. Most of the cases had a mild skin involvement and only one case required OCR discontinuation. No association with arthritis, personal or family history of psoriasis was found. Data compiled suggests that PsD tends to appear within the first year of treatment. There are few studies focusing on B‐lymphocytes in psoriasis and several hypotheses attempt to explain their role. The most widely accepted is the depletion of regulatory B‐lymphocytes with immunomodulatory function through interleukin‐10. However, the exact mechanism by which this occurs with OCR remains unclear and the presented case of anti‐CD20‐induced PsD highlights the importance of continuous monitoring of new treatments in terms of dermatological side effects and the induction of skin diseases, in particular psoriasis. There is also a need to inform the professional community about the possibility of psoriasis in patients with multiple sclerosis and the consequences of this condition.

Abstract Objective The primary aim of this study was to evaluate the influence of targeted interventions, administered through comprehensive geriatric assessments on the incidence of hospitalization‐related complications among older adults diagnosed with pulmonary diseases. Methods A retrospective analysis of medical records encompassed individuals aged 75 years and older who were admitted to a lung center during the period spanning from March to June 2023. These admissions occurred in a context where standardized geriatric management protocols were systematically implemented. This study's scope extended to assessing the prevalence of hospital‐related complications, encompassing delirium and pressure ulcers. A rigorous multivariate logistic regression analysis was conducted to discern and characterize associated factors. Results The integration of comprehensive geriatric assessment yielded a substantial reduction in in‐hospital complications among the cohort of 118 patients (mean age : 82.1 ± 5.6 years, 44.5% women). The incidence of delirium decreased from 53.3% to 21.8% [odds ratio (OR): 0.246, 95% confidence interval (CI): 0.134–0.450, p

Abstract The gene dosage compensation hypothesis presents a mechanism through which the expression of certain genes is modulated to compensate for differences in the dose of genes when additional chromosomes are present. It is one of the means through which cancer cells actively cope with the potential damaging effects of aneuploidy, a hallmark of most cancers. Dosage compensation arises through several processes, including downregulation or overexpression of specific genes and the relocation of dosage‐sensitive genes. In cancer, a majority of compensated genes are generally thought to be regulated at the translational or post‐translational level, and include the basic components of a compensation loop, including sensors of gene dosage and modulators of gene expression. Post‐translational regulation is mostly undertaken by a general degradation or aggregation of remaining protein subunits of macromolecular complexes. An increasingly important role has also been observed for transcriptional level regulation. This article reviews the process of targeted gene dosage compensation in cancer and other biological conditions, along with the mechanisms by which cells regulate specific genes to restore cellular homeostasis. These mechanisms represent potential targets for the inhibition of dosage compensation of specific genes in aneuploid cancers. This article critically examines the process of targeted gene dosage compensation in cancer and other biological contexts, alongside the criteria for identifying genes subject to dosage compensation and the intricate mechanisms by which cells orchestrate the regulation of specific genes to reinstate cellular homeostasis. Ultimately, our aim is to gain a comprehensive understanding of the intricate nature of a systems‐level property. This property hinges upon the kinetic parameters of regulatory motifs, which we have termed “gene dosage sensor loops.” These loops have the potential to operate at both the transcriptional and translational levels, thus emerging as promising candidates for the inhibition of dosage compensation in specific genes. Additionally, they represent novel and highly specific therapeutic targets in the context of aneuploid cancer.

Abstract Models derived from satellite image data are needed to monitor the status of terrestrial ecosystems across large spatial scales. However, a remote sensing‐based approach to quantify soil multifunctionality at the global scale is missing despite significant research efforts on this topic. A major constraint for doing so is the availability of suitable global‐scale field data to calibrate remote sensing indicators (RSI) and, to a lesser extent, the sensitivity of spectral data of available satellite sensors to soil background and atmospheric conditions. Here, we aimed to develop a soil multifunctionality model to monitor global drylands coupling ground data on 14 soil functions of 222 dryland areas from six continents to 18 RSI derived from a time series (2006–2013) Landsat dataset. Among the RSI evaluated, the chlorophyll absorption ratio index was the best predictor of soil multifunctionality in single‐variable‐based models (r = 0.66, P

Abstract Objectives Periodontal disease is understood to be a result of dysbiotic interactions between the host and the biofilm, causing a unique reaction for each individual, which in turn characterizes their susceptibility. The objective of this study was to chronologically evaluate periodontal tissue destruction induced by systemic bacterial challenge in known susceptible (BALB/c) and resistant (C57BL/6) mouse lineages. Material and Methods Animals, 6–8 weeks old, were allocated into three experimental groups: Negative control (C), Gavage with sterile carboxymethyl cellulose 2%—without bacteria (Sham), and Gavage with carboxymethyl cellulose 2% + Porphyromonas gingivalis (Pg‐W83). Before infection, all animals received antibiotic treatment (sulfamethoxazole/trimethoprim, 400/80 mg/5 mL) for 7 days, followed by 3 days of rest. Microbial challenge was performed 3 times per week for 1, 2, or 3 weeks. After that, the animals were kept until the completion of 42 days of experiments, when they were euthanized. The alveolar bone microarchitecture was assessed by computed microtomography. Results Both C57BL/6 and BALB/c mice exhibited significant bone volume loss and lower trabecular thickness as well as greater bone porosity compared to the (C) and (Sham) groups after 1 week of microbial challenge (p

Abstract The difficulty in predicting fatal outcomes in patients with coronavirus disease 2019 (COVID‐19) impacts the general morbidity and mortality due to severe acute respiratory syndrome‐coronavirus 2 infection, as it wears out the hospital services that care for these patients. Unfortunately, in several of the candidates for prognostic biomarkers proposed, the predictive power is compromised when patients have pre‐existing comorbidities. A cohort of 147 patients hospitalized for severe COVID‐19 was included in a descriptive, observational, single‐center, and prospective study. Patients were recruited during the first COVID‐19 pandemic wave (April–November 2020). Data were collected from the clinical history whereas immunophenotyping by multiparameter flow cytometry analysis allowed us to assess the expression of surface markers on peripheral leucocyte. Patients were grouped according to the outcome in survivors or non‐survivors. The prognostic value of leucocyte, cytokines or HLA‐DR, CD39, and CD73 was calculated. Hypertension and chronic renal failure but not obesity and diabetes were conditions more frequent among the deceased patient group. Mixed hypercytokinemia, including inflammatory (IL‐6) and anti‐inflammatory (IL‐10) cytokines, was more evident in deceased patients. In the deceased patient group, lymphopenia with a higher neutrophil‐lymphocyte ratio (NLR) value was present. HLA‐DR expression and the percentage of CD39+ cells were higher than non‐COVID‐19 patients but remained similar despite the outcome. Receiver operating characteristic analysis and cutoff value of NLR (69.6%, 9.4), percentage NLR (pNLR; 71.1%, 13.6), and IL‐6 (79.7%, 135.2 pg/mL). The expression of HLA‐DR, CD39, and CD73, as many serum cytokines (other than IL‐6) and chemokines levels do not show prognostic potential, were compared to NLR and pNLR values.

Abstract A feeding trial with Macrobrachium acanthurus juveniles was performed to determine growth performance and utilization of diets varying in protein, lipid, and carbohydrate level. Twelve diets were formulated with three levels of protein (P) and supplemented with different proportions of lipids (L) and carbohydrates (C): P30‐L20‐C8, P30‐L15‐C19, P30‐L12‐C25, P30‐L10‐C31, P35‐L20‐C3, P35‐L15‐C15, P35‐L10‐C26, P35‐L5‐C38, P40‐L15‐C8, P40‐L10‐C19, P40‐L5‐C31, and P40‐L1‐C40. Lipids and carbohydrates were added allowing an overall energy content limit of 400 kcal per 100 g of diet. Each diet was fed to triplicate groups of juveniles with an initial weight of 60.9 ± 10.9 mg (mean ± SD) for 60 days. Overall growth performance and gene expression of fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucose‐6‐phosphatase (G6P), and hexokinase (HK) in the hepatopancreas were assessed. Highest weight gain values and specific growth rates were observed in prawns fed diets with 35% of protein inclusion. Expression of FAS was downregulated when fed 30% of protein. Results indicate M. acanthurus use protein as their primary source of energy and when this is low in the diet, lipids are used to spare the energy from proteins. Suggested inclusion of protein, lipids, and carbohydrates in diets for M. acanthurus should be 35%, 15%, and 15%, respectively.