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Understanding and modeling perceived properties of sky-dome illumination is an important but challenging problem due to the interplay of several factors such as the materials and geometries of the objects present in the scene being observed. Existing models of sky-dome illumination focus on the physical properties of the sky. However, these parametric models often do not align well with the properties perceived by a human observer. In this work, drawing inspiration from the Hosek-Wilkie sky-dome model, we investigate the perceptual properties of outdoor illumination. For this purpose, we perform a large-scale user study via crowdsourcing to collect a dataset of perceived illumination properties (scattering, glare, and brightness) for different combinations of geometries and materials under a variety of outdoor illuminations, totaling 5,000 distinct images. We perform a thorough statistical analysis of the collected data which reveals several interesting effects. For instance, our analysis shows that when there are objects in the scene made of rough materials, the perceived scattering of the sky increases. Furthermore, we utilize our extensive collection of images and their corresponding perceptual attributes to train a predictor. This predictor, when provided with a single image as input, generates an estimation of perceived illumination properties that align with human perceptual judgments. Accurately estimating perceived illumination properties can greatly enhance the overall quality of integrating virtual objects into real scene photographs. Consequently, we showcase various applications of our predictor. For instance, we demonstrate its utility as a luminance editing tool for showcasing virtual objects in outdoor scenes.

Introduction: Aryl-alcohol oxidase (AAO) shows a pronounced duality as oxidase and dehydrogenase similar to that described for other glucose-methanol-choline (GMC) oxidase/dehydrogenase superfamily proteins involved in lignocellulose decomposition. In this work, we detail the overall mechanism of AAOs from Pleurotus eryngii and Bjerkandera adusta for catalyzing the oxidation of natural aryl-alcohol substrates using either oxygen or quinones as electron acceptors and describe the crystallographic structure of AAO from B. adusta in complex with a product analogue. Methods: Kinetic studies with 4-methoxybenzyl and 3-chloro-4- methoxybenzyl alcohols, including both transient-state and steady-state analyses, along with interaction studies, provide insight into the oxidase and dehydrogenase mechanisms of these enzymes. Moreover, the resolution of the crystal structure of AAO from B. adusta allowed us to compare their overall folding and the structure of the active sites of both AAOs in relation to their activities. Results and Discussion: Although both enzymes show similar mechanistic properties, notable differences are highlighted in this study. In B. adusta , the AAO oxidase activity is limited by the reoxidation of the flavin, while in P. eryngii the slower step takes place during the reductive half-reaction, which determines the overall reaction rate. By contrast, dehydrogenase activity in both enzymes, irrespective of the alcohol participating in the reaction, is limited by the hydroquinone release from the active site. Despite these differences, both AAOs are more efficient as dehydrogenases, supporting the physiological role of this activity in lignocellulosic decay. This dual activity would allow these enzymes to adapt to different environments based on the available electron acceptors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Serrano, Cinca-Fernando, Carro, Velázquez-Campoy, Martínez-Júlvez, Martínez and Ferreira.)

Acute pancreatitis is the leading cause of inpatient care among gastrointestinal conditions. Despite early intervention, one-third of patients experience recurrent acute pancreatitis (RAP). A comprehensive diagnostic approach is warranted to identify and treat underlying factors in order to prevent recurrence. RAP is most frequent among men aged 30-40, smokers, and in those with excessive alcohol consumption. To identify the etiology is paramount to stratify patients according to their individual risk of RAP and for predicting an eventual evolution to chronic pancreatitis. Although the initial management of acute pancreatitis is widely homogeneous according to established guidelines, there are no defined protocols to investigate RAP. In the present editorial article we propose a structured algorithm with precise recommendations to investigate the etiology RAP as part of routine clinical practice. Although there are relevant knowledge gaps in this disease, we believe that our guidance would contribute for a more homogenous diagnostic approach of RAP in clinical practice.

Patients diagnosed with obesity are prescribed opioid medications at a higher rate than the general population; however, it is not known if eating a high fat diet might impact individual sensitivity to these medications. To explore the hypothesis that eating a high fat diet increases sensitivity of rats to the effects of morphine, 24 female Sprague-Dawley rats (n=8/diet) ate either a standard laboratory chow (17% kcal from fat), a high fat/low carbohydrate (ketogenic) chow (90.5% kcal from fat), or a traditional high fat/high carbohydrate chow (60% kcal from fat). Morphine-induced antinociception was assessed using a warm water tail withdrawal procedure, during which latency (in seconds) for rats to remove their tail from warm water baths was recorded following saline or morphine (0.32-56 mg/kg, IP) injections. Morphine was administered acutely and chronically, which involved 19 days of twice daily injections (increasing in 1/4 log dose increments every 3 days: 3.2-56 mg/kg, IP) to induce dependence and assess tolerance. The adverse effects of morphine (i.e., tolerance, withdrawal, changes in body temperature) were assessed throughout the study. Morphine induced comparable antinociception in rats eating different diets, and all rats developed tolerance following chronic morphine exposure. Additional adverse effects of morphine were also comparable among rats eating different diets; however, withdrawal-induced weight loss was less severe for rats eating ketogenic chow. These results suggest that dietary manipulation might modulate the severity of withdrawal-related weight loss, in ways that could be relevant for patients. Significance Statement The present study in female rats suggests that eating a high fat/low carbohydrate (ketogenic) or a traditional high fat/high carbohydrate diet does not impact the pain-relieving or adverse effects of opioids (i.e., tolerance or withdrawal). However, eating a ketogenic diet may have beneficial effects on opioid withdrawal-related weight loss. Individuals diagnosed with obesity taking opioids for pain-related conditions might therefore consider adopting a ketogenic diet when opioid administration is discontinued to potentially mitigate withdrawal-related weight loss., (Copyright © 2024 American Society for Pharmacology and Experimental Therapeutics.)

In their seminal experiment in 1944, Heider and Simmel revealed that humans have a pronounced tendency to impose narrative meaning even in the presence of simple animations of geometric shapes. Despite the shapes having no discernible features or emotions, participants attributed strong social context, meaningful interactions, and even emotions to them. This experiment, run on traditional 2D displays has since had a significant impact on fields ranging from psychology to narrative storytelling. Virtual Reality (VR), on the other hand, offers a significantly new viewing paradigm, a fundamentally different type of experience with the potential to enhance presence, engagement and immersion. In this work, we explore and analyze to what extent the findings of the original experiment by Heider and Simmel carry over into a VR setting. We replicate such experiment in both traditional 2D displays and with a head mounted display (HMD) in VR, and use both subjective (questionnaire-based) and objective (eye-tracking) metrics to record the observers' visual behavior. We perform a thorough analysis of this data, and propose novel metrics for assessing the observers' visual behavior. Our questionnaire-based results suggest that participants who viewed the animation through a VR headset developed stronger emotional connections with the geometric shapes than those who viewed it on a traditional 2D screen. Additionally, the analysis of our eye-tracking data indicates that participants who watched the animation in VR exhibited fewer shifts in gaze, suggesting greater engagement with the action. However, we did not find evidence of differences in how subjects perceived the roles of the shapes, with both groups interpreting the animation's plot at the same level of accuracy. Our findings may have important implications for future psychological research using VR, especially regarding our understanding of social cognition and emotions., (© 2024. The Author(s).)

Climate change is an environmental emergency threatening species and ecosystems globally. Oceans have absorbed about 90% of anthropogenic heat and 20%-30% of the carbon emissions, resulting in ocean warming, acidification, deoxygenation, changes in ocean stratification and nutrient availability, and more severe extreme events. Given predictions of further changes, there is a critical need to understand how marine species will be affected. Here, we used an integrated risk assessment framework to evaluate the vulnerability of 132 chondrichthyans in the Eastern Tropical Pacific (ETP) to the impacts of climate change. Taking a precautionary view, we found that almost a quarter (23%) of the ETP chondrichthyan species evaluated were highly vulnerable to climate change, and much of the rest (76%) were moderately vulnerable. Most of the highly vulnerable species are batoids (77%), and a large proportion (90%) are coastal or pelagic species that use coastal habitats as nurseries. Six species of batoids were highly vulnerable in all three components of the assessment (exposure, sensitivity and adaptive capacity). This assessment indicates that coastal species, particularly those relying on inshore nursery areas are the most vulnerable to climate change. Ocean warming, in combination with acidification and potential deoxygenation, will likely have widespread effects on ETP chondrichthyan species, but coastal species may also contend with changes in freshwater inputs, salinity, and sea level rise. This climate-related vulnerability is compounded by other anthropogenic factors, such as overfishing and habitat degradation already occurring in the region. Mitigating the impacts of climate change on ETP chondrichthyans involves a range of approaches that include addressing habitat degradation, sustainability of exploitation, and species-specific actions may be required for species at higher risk. The assessment also highlighted the need to further understand climate change's impacts on key ETP habitats and processes and identified knowledge gaps on ETP chondrichthyan species., (© 2024 The Author(s). Global Change Biology published by John Wiley & Sons Ltd.)

Background: Effective communication is founded on bidirectional participation from families and healthcare providers. In adult medicine, bidirectional communication promotes treatment adherence and builds the family-provider relationship. However, the relationship between communication styles in pediatrics remains poorly understood, particularly in culturally diverse settings. This study aims to investigate parent-provider communication dynamics and parental involvement during diagnostic cancer communication in Guatemala., Procedure: This qualitative study included 20 families of children with cancer and 10 providers at Unidad Nacional de Oncología Pediátrica in Guatemala. Psychoeducation and diagnostic conversations between parents, psychologists, and oncologists were recorded and thematically analyzed using a priori and novel codes exploring communication behaviors, parental engagement, and interpersonal dynamics., Results: Participating parents had children with various diagnoses. Only 15% of fathers and 5% of mothers reported education beyond primary school. Providers spoke 68% of words during psychoeducation and 85% of words during diagnosis conversations. Providers used supportive communication behaviors providing explanations, demonstrating verbal attentiveness, and soliciting questions and non-supportive behaviors including paternalistic talk. Parental participation was considered active when they asked questions, expressed hopes or concerns, or asserted their opinions, and non-active when participation was limited to brief responses to closed-ended questions. Supportive provider communication often encouraged active participation; non-supportive communication did not. Furthermore, active parental participation prompted supportive communication from providers, while non-active participation did not., Conclusions: Our findings highlight the bidirectional nature of effective communication, establishing that provider communication styles both influence and are influenced by parental participation, and emphasizing the importance of supportive provider communication for patient-centered care., (© 2024 Wiley Periodicals LLC.)

Voltage-gated Ca V 2.1 (P/Q-type) Ca 2+ channels play a crucial role in regulating neurotransmitter release, thus contributing to synaptic plasticity and to processes such as learning and memory. Despite their recognized importance in neural function, there is limited information on their potential involvement in neurodegenerative conditions such as Alzheimer's disease (AD). Here, we aimed to explore the impact of AD pathology on the density and nanoscale compartmentalization of Ca V 2.1 channels in the hippocampus in association with GABA B receptors. Histoblotting experiments showed that the density of Ca V 2.1 channel was significantly reduced in the hippocampus of APP/PS1 mice in a laminar-dependent manner. Ca V 2.1 channel was enriched in the active zone of the axon terminals and was present at a very low density over the surface of dendritic tree of the CA1 pyramidal cells, as shown by quantitative SDS-digested freeze-fracture replica labelling (SDS-FRL). In APP/PS1 mice, the density of Ca V 2.1 channel in the active zone was significantly reduced in the strata radiatum and lacunosum-moleculare, while it remained unaltered in the stratum oriens. The decline in Cav2.1 channel density was found to be associated with a corresponding impairment in the GABAergic synaptic function, as evidenced by electrophysiological experiments carried out in the hippocampus of APP/PS1 mice. Remarkably, double SDS-FRL showed a co-clustering of Ca V 2.1 channel and GABA B1 receptor in nanodomains (~40-50 nm) in wild type mice, while in APP/PS1 mice this nanoarchitecture was absent. Together, these findings suggest that the AD pathology-induced reduction in Ca V 2.1 channel density and Ca V 2.1-GABA B1 de-clustering may play a role in the synaptic transmission alterations shown in the AD hippocampus. Therefore, uncovering these layer-dependent changes in P/Q calcium currents associated with AD pathology can benefit the development of future strategies for AD management., (© 2024 The Author(s). Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

There is growing interest in clozapine clinical use, monitoring, and research, particularly adverse drug reactions (ADRs) other than agranulocytosis. In this study we focused on clozapine pharmacovigilance. Hence, we contacted clinicians and researchers in Latin America and requested information about local psychiatric services, clozapine availability, clinical use, and ADR monitoring with the VigiBase system. Only two countries have the minimum recommended number of psychiatric beds (15 per 100,000 residents): Uruguay (N = 34.9) and Argentina (N = 17). Bolivia is the only country where clozapine is unavailable. Nine out of twenty countries (45 %) reported ADRs to VigiBase. Argentina, Brazil, Chile, Colombia, and Mexico published national guidelines for schizophrenia treatment. Chile is the sole country with clozapine clinics with drug serum monitoring. Ethnicity-related drug titration in not described in package inserts in any country. We examined in detail the 9 most frequent and important clozapine ADRs in the worldwide database (pneumonia, sudden death, cardiac arrest, agranulocytosis, myocarditis, constipation, arrhythmia, seizure, and syncope). These 9 ADRs led to 294 reports with fatal outcomes in Argentina (N = 3), Brazil (N = 3), Chile (N = 2), and Peru (N = 1). Agranulocytosis was reported from 7 countries: constipation or seizures from 8 countries. Only two countries reported pneumonia and one country reported myocarditis. The number of clozapine reports in VigiBase has no relationship to the country's population. All Latin American countries underreport clozapine associated ADRs. Latin American governments, along with clinicians, researchers, and educators, should optimize clozapine use and monitoring for the benefit of people with severe mental and some neurological disorders., Competing Interests: Declaration of competing interest In the last 3 years, the other authors report no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The quality and quantity of clozapine safety monitoring considerably differs among South American countries and mainly focus on hematological surveillance. Few studies have been conducted on other clozapine-related adverse effects (ADRs) and mainly refer to case reports and literature reviews. We retrieved thirty-nine publications on clozapine related ADRs others than neutropenia. Studies in Brazil and Venezuela accounted for 67 % of all the publications, and 8 out of 12 countries published 2 or less manuscripts. Only Chile offers serum clozapine level measurement in public institutions. Given the recently recognized role of ethnicity, gender, smoking, obesity drug interactions in optimal clozapine administration, modernization of clozapine clinical use and research in psychiatry and neurology most be broadcasted and stimulated in South American countries., Competing Interests: Declaration of competing interest The authors report no competing conflicts of interest concerning the manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: Stigma is an understudied barrier to health care acceptance in pediatric oncology. We sought to explore the stigma experience, including its impact on cancer treatment decision making, and identify strategies to mitigate stigma for patients with osteosarcoma and retinoblastoma in Guatemala, Jordan, and Zimbabwe., Methods: Participants included caregivers, adolescent patients (age 12-19 years), and health care clinicians. A semistructured interview guide based on The Health Stigma and Discrimination Framework (HSDF) was adapted for use at each site. Interviews were conducted in English, Spanish, Arabic, or Shona, audio-recorded, translated, and transcribed. Thematic analysis focused on stigma practices, experiences, outcomes, drivers, mitigators, and interventions., Results: We conducted 56 interviews (28 caregivers, 19 health care clinicians, nine patients; 20 in Guatemala, 21 in Jordan, 15 in Zimbabwe). Major themes were organized into categories used to adapt the HSDF to global pediatric cancer care. Themes were described similarly across all sites, ages, and diagnoses, with specific cultural nuances noted. Pediatric cancer stigma was depicted as an isolating and emotional experience beginning at diagnosis and including internalized and associative stigma. Stigma affected decision making and contributed to negative outcomes including delayed diagnosis, treatment abandonment, regret, and psychosocial fragility. Overcoming stigma led to positive outcomes including resilience, treatment adherence, pride, and advocacy. Identified stigma drivers and mitigators were linked to potential interventions., Conclusion: Participants describe a shared stigma experience that transcends geography, cultural context, age, and diagnosis. Stigma manifestations have the potential to impact medical decision making and affect long-term psychological outcomes. Stigma assessment tools and interventions aimed at stigma mitigation including educational initiatives and support groups specific to pediatric cancer should be the focus of future research.

Background: Pseudomyxoma peritonei (PMP) is a rare peritoneal mucinous carcinomatosis with largely unknown underlying molecular mechanisms. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the only therapeutic option; however, despite its use, recurrence with a fatal outcome is common. The lack of molecular characterisation of PMP and other mucinous tumours is mainly due to the physicochemical properties of mucin., Results: This manuscript describes the first protocol capable of breaking the mucin barrier and isolating proteins from mucinous tumours. Briefly, mucinous tumour samples were homogenised and subjected to liquid chromatography using two specific columns to reduce mainly glycoproteins, albumins and immunoglobulin G. The protein fractions were then subjected to mass spectrometry analysis and the proteomic profile obtained was analysed using various bioinformatic tools. Thus, we present here the first proteome analysed in PMP and identified a distinct mucin isoform profile in soft compared to hard mucin tumour tissues as well as key biological processes/pathways altered in mucinous tumours. Importantly, this protocol also allowed us to identify MUC13 as a potential tumour cell marker in PMP., Conclusions: In sum, our results demonstrate that this protein isolation protocol from mucin will have a high impact, allowing the oncology research community to more rapidly advance in the knowledge of PMP and other mucinous neoplasms, as well as develop new and effective therapeutic strategies., (© 2024. The Author(s).)

Sertraline is a commonly used antidepressant of the selective serotonin reuptake inhibitors (SSRIs) class. In this study, we have used the patch-clamp technique to assess the effects of sertraline on Kv2.1 channels heterologously expressed in HEK-293 cells and on the voltage-gated potassium currents (I Kv ) of Neuro 2a cells, which are predominantly mediated by Kv2.1 channels. Our results reveal that sertraline inhibits Kv2.1 channels in a concentration-dependent manner. The sertraline-induced inhibition was not voltage-dependent and did not require the channels to be open. The kinetics of activation and deactivation were accelerated and decelerated, respectively, by sertraline. Moreover, the inhibition by this drug was use-dependent. Notably, sertraline significantly modified the inactivation mechanism of Kv2.1 channels; the steady-state inactivation was shifted to hyperpolarized potentials, the closed-state inactivation was enhanced and accelerated, and the recovery from inactivation was slowed, suggesting that this is the main mechanism by which sertraline inhibits Kv2.1 channels. Overall, this study provides novel insights into the pharmacological actions of sertraline on Kv2.1 channels, shedding light on the intricate interaction between SSRIs and ion channel function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Humans perceive the world by integrating multimodal sensory feedback, including visual and auditory stimuli, which holds true in virtual reality (VR) environments. Proper synchronization of these stimuli is crucial for perceiving a coherent and immersive VR experience. In this work, we focus on the interplay between audio and vision during localization tasks involving natural head-body rotations. We explore the impact of audio-visual offsets and rotation velocities on users' directional localization acuity for various viewing modes. Using psychometric functions, we model perceptual disparities between visual and auditory cues and determine offset detection thresholds. Our findings reveal that target localization accuracy is affected by perceptual audio-visual disparities during head-body rotations, but remains consistent in the absence of stimuli-head relative motion. We then showcase the effectiveness of our approach in predicting and enhancing users' localization accuracy within realistic VR gaming applications. To provide additional support for our findings, we implement a natural VR game wherein we apply a compensatory audio-visual offset derived from our measured psychometric functions. As a result, we demonstrate a substantial improvement of up to 40% in participants' target localization accuracy. We additionally provide guidelines for content creation to ensure coherent and seamless VR experiences.

Ginseng, a popular herbal supplement among athletes, is believed to enhance exercise capacity and performance. This study investigated the short-term effects of Panax ginseng extract (PG) on aerobic capacity, lipid profile, and cytokines. In a 14-day randomized, double-blind trial, male participants took 500 mg of PG daily. Two experiments were conducted: one in 10 km races ( n = 31) and another in a laboratory-controlled aerobic capacity test ( n = 20). Blood lipid and cytokine profile, ventilation, oxygen consumption, hemodynamic and fatigue parameters, and race time were evaluated. PG supplementation led to reduced total blood lipid levels, particularly in triacylglycerides (10 km races -7.5 mg/dL (95% CI -42 to 28); sub-maximal aerobic test -14.2 mg/dL (95% CI -52 to 23)), while post-exercise blood IL-10 levels were increased (10 km 34.0 pg/mL (95% CI -2.1 to 70.1); sub-maximal aerobic test 4.1 pg/mL (95% CI -2.8 to 11.0)), and oxygen consumption decreased during the sub-maximal aerobic test (VO 2 : -1.4 mL/min/kg (95% CI -5.8 to -0.6)). No significant differences were noted in race time, hemodynamic, or fatigue parameters. Overall, PG supplementation for 2 weeks showed benefits in blood lipid profile and energy consumption during exercise among recreational athletes. This suggests a potential role for PG in enhancing exercise performance and metabolic health in this population.

Voltage-gated Na v 1.5 channels are central to the generation and propagation of cardiac action potentials 1 . Aberrations in their function are associated with a wide spectrum of cardiac diseases including arrhythmias and heart failure 2-5 . Despite decades of progress in Na v 1.5 biology 6-8 , the lack of structural insights into intracellular regions has hampered our understanding of its gating mechanisms. Here we present three cryo-EM structures of human Na v 1.5 in previously unanticipated open states, revealing sequential conformational changes in gating charges of the voltage-sensing domains (VSDs) and several intracellular regions. Despite the channel being in the open state, these structures show the IFM motif repositioned in the receptor site but not dislodged. In particular, our structural findings highlight a dynamic C-terminal domain (CTD) and III-IV linker interaction, which regulates the conformation of VSDs and pore opening. Electrophysiological studies confirm that disrupting this interaction results in the fast inactivation of Na v 1.5. Together, our structure-function studies establish a foundation for understanding the gating mechanisms of Na v 1.5 and the mechanisms underlying CTD-related channelopathies., Competing Interests: Competing interests The authors declare that they have no competing interests.

Subtype 5 metabotropic glutamate receptors (mGlu 5 ) are known to play an important role in regulating cognitive, social and valence systems. However, it remains largely unknown at which circuits and neuronal types mGlu 5 act to influence these behavioral domains. Altered tissue- or cell-specific expression or function of mGlu 5 has been proposed to contribute to the exacerbation of neuropsychiatric disorders. Here, we examined how these receptors regulate the activity of somatostatin-expressing (SST+) neurons, as well as their influence on behavior and brain rhythmic activity. Loss of mGlu 5 in SST+ neurons elicited excitatory synaptic dysfunction in a region and sex-specific manner together with a range of emotional imbalances including diminished social novelty preference, reduced anxiety-like behavior and decreased freezing during retrieval of fear memories. In addition, the absence of mGlu 5 in SST+ neurons during fear processing impaired theta frequency oscillatory activity in the medial prefrontal cortex and ventral hippocampus. These findings reveal a critical role of mGlu 5 in controlling SST+ neurons excitability necessary for regulating negative emotional states., (© 2024. The Author(s).)

Hydrolytic enzymes play crucial roles in cellular processes, and dysregulation of their activities is implicated in various physiological and pathological conditions. These enzymes cleave substrates such as peptide bonds, phosphodiester bonds, glycosidic bonds, and other esters. Detecting aberrant hydrolase activity is vital for understanding disease mechanisms and developing targeted therapeutic interventions. This study introduces a novel approach to measuring hydrolase activity using giant magnetoresistive (GMR) spin valve sensors. These sensors change resistance in response to magnetic fields, and here, they are functionalized with specific substrates for hydrolases conjugated to magnetic nanoparticles (MNPs). When a hydrolase cleaves its substrate, the tethered magnetic nanoparticle detaches, causing a measurable shift in the sensor's resistance. This design translates hydrolase activity into a real-time, activity-dependent signal. The assay is simple, rapid, and requires no washing steps, making it ideal for point-of-care settings. Unlike fluorescent methods, it avoids issues like autofluorescence and photobleaching, broadening its applicability to diverse biofluids. Furthermore, the sensor array contains 80 individually addressable sensors, allowing for the simultaneous measurement of multiple hydrolases in a single reaction. The versatility of this method is demonstrated with substrates for nucleases, Bcu I and DNase I, and the peptidase, human neutrophil elastase. To demonstrate a clinical application, we show that neutrophil elastase in sputum from cystic fibrosis patients hydrolyze the peptide-GMR substrate, and the cleavage rate strongly correlates with a traditional fluorogenic substrate. This innovative assay addresses challenges associated with traditional enzyme measurement techniques, providing a promising tool for real-time quantification of hydrolase activities in diverse biological contexts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sveiven, Serrano, Rosenberg, Conrad, Hall and O’Donoghue.)

Introduction: Respiratory syncytial virus (RSV) causes an acute respiratory illness similar to influenza, although there are few data comparing both of them in adults. The existence of clinical differences between these two infections could have implications for their management., Materials and Methods: Retrospective observational cohort study including 63 adults with positive PCR for RSV and 221 for influenza during winter 2018-2019. Epidemiological, clinical characteristics and outcomes were contrasted between both groups., Results: Compared to influenza, RSV-positive patients presented a higher association with active neoplasia (OR=2.9; 95% CI: 1.2-6.9), dependence for basic activities of daily living (OR=3.4; 95% CI: 1.4-8.2) and immunosuppression due to chronic glucocorticoid administration (OR=7.6; 95% CI: 1.6-36.1). At diagnosis, fever was less common (OR=0.3; 95% CI: 0.2-0.7), and C-reactive protein level ≥100mg/l was more frequent (OR=2.1; 95% CI: 1.0-4.5). They developed bacterial co-infection by Staphylococcus aureus in a higher proportion (OR=8.3; 95% CI: 1.5-46.9) and presented a greater need for admission to the intensive care unit (OR=5.4; 95% CI: 1.4-19.2)., Conclusion: RSV is an important cause of respiratory illness in adults during the influenza season. It especially affects vulnerable patients with chronic underlying diseases, and has a higher morbidity than influenza. For all these reasons, specific detection, prevention and treatment of RSV is necessary in order to reduce the consumption of health care resources due to RSV disease in adults., (Copyright © 2022 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Background: High CO 2 pneumoperitoneum pressure during laparoscopy adversely affects the peritoneal environment. This study hypothesized that low pneumoperitoneum pressure may be linked to less peritoneal damage and possibly to better clinical outcomes., Materials and Methods: One hundred patients undergoing scheduled laparoscopic cholecystectomy were randomized 1:1 to low or to standard pneumoperitoneum pressure. Peritoneal biopsies were performed at baseline time and 1 hour after peritoneum insufflation in all patients. The primary outcome was peritoneal remodeling biomarkers and apoptotic index. Secondary outcomes included biomarker differences at the studied times and some clinical variables such as length of hospital stay, and quality and safety issues related to the procedure., Results: Peritoneal IL6 after 1 hour of surgery was significantly higher in the standard than in the low-pressure group (4.26±1.34 vs. 3.24±1.21; P =0.001). On the contrary, levels of connective tissue growth factor and plasminogen activator inhibitor-I were higher in the low-pressure group (0.89±0.61 vs. 0.61±0.84; P =0.025, and 0.74±0.89 vs. 0.24±1.15; P =0.028, respectively). Regarding apoptotic index, similar levels were found in both groups and were 44.0±10.9 and 42.5±17.8 in low and standard pressure groups, respectively. None of the secondary outcomes showed differences between the 2 groups., Conclusions: Peritoneal inflammation after laparoscopic cholecystectomy is higher when surgery is performed under standard pressure. Adhesion formation seems to be less in this group. The majority of patients undergoing surgery under low pressure were operated under optimal workspace conditions, regardless of the surgeon's expertise., Competing Interests: A.B.S., O.D.-C., and A.S. report personal fees from Merck Sharp & Dohme. J.M.-B. is a researcher at FIBio-HRC and supported by the Consejería de Sanidad (Comunidad Autónoma de Madrid). The remaining authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Persons with achondroplasia develop early obesity, which is a comorbidity associated with other complications. Currently, there are no validated specific predictive equations to estimate resting energy expenditure in achondroplasia., Methods: We analyzed the influence of body composition on this parameter and determined whether predictive models used for children with standard height are adjusted to achondroplasia. In this cross-sectional study, we measured anthropometric parameters in children with achondroplasia. Fat mass was obtained using the Slaughter skinfold-thickness equation and resting energy expenditure was determined with a Fitmate-Cosmed calorimeter and with predictive models validated for children with average height (Schofield, Institute of Medicine, and Tverskaya)., Results: All of the equations yielded a lower mean value than resting energy expenditure with indirect calorimetry (1256±200 kcal/day [mean±SD]) but the closest was the Tverskaya equation (1017 ± 64 kcal/day), although the difference remained statistically significant. We conclude that weight and height have the greatest influence on resting energy expenditure., Conclusion: We recommend studying the relationship between body composition and energy expenditure in achondroplasia in more depth. In the absence of valid predictive models suitable for clinical use to estimate body composition and resting energy expenditure in achondroplasia, it is recommended to use the gold standard methods by taking into account certain anthropometric parameters., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Volatile organic compounds (VOCs) play a crucial role in the formation of ozone (O 3 ) and secondary organic aerosol (SOA). We conducted measurements of VOC ambient mixing ratios during both summer and winter at two stations: a Barcelona urban background station (BCN) and the Montseny rural background station (MSY). Subsequently, we employed positive matrix factorization (PMF) to analyze the VOC mixing ratios and identify their sources. Our analysis revealed five common sources: anthropogenic I (traffic & industries); anthropogenic II (traffic & biomass burning); isoprene oxidation; monoterpenes; long-lifetime VOCs. To assess the impact of these VOCs on the formation of secondary pollutants, we calculated the ozone formation potential (OFP) and secondary organic aerosol formation potential (SOAP) associated with each VOC. In conclusion, our study provides insights into the sources of VOCs and their contributions to the formation of ozone and SOA in NE Spain. The OFP was primarily influenced by anthropogenic aromatic compounds from the traffic & industries source at BCN (38-49 %) and during winter at MSY (34 %). In contrast, the summer OFP at MSY was primarily driven by biogenic contributions from monoterpenes and isoprene oxidation products (45 %). Acetaldehyde (10-35 %) and methanol (13-14 %) also made significant OFP contributions at both stations. Anthropogenic aromatic compounds originating from traffic, industries, and biomass burning played a dominant role (88-93 %) in SOA formation at both stations during both seasons. The only exception was during the summer at MSY, where monoterpenes became the primary driver of SOA formation (41 %). These findings emphasize the importance of considering both anthropogenic and biogenic VOCs in air quality management strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

In this paper, we present the results of a research experience of implementing andragogy in a learning environment designed to better meet the needs of adult learners studying part-time at a distance university. The learning environment was composed of a learning experience on a formal distance university online course that has been enriched with a non-formal component based on students' participation in a Massive Online Open Course (MOOC) related to the same topic. The non-formal experience was designed to consolidate the learning of specific content that involved difficult concepts and foster collaborative skills. The university online course is in the field of computer science and human-computer interaction. The instructional design, including the course assignments, has been guided by Knowles' principles of andragogy. Results from the data analysis of five years of academic results and student satisfaction has helped to understand the learning experience from including a MOOC in adult distance formal learning., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Descriptions on impact of SARS-CoV-2 infection in patients with cardiac amyloidosis (CA) are lacking. Our aim was to describe the prognosis of those patients., Methods: Retrospective observational study of unvaccinated patients with CA who developed SARS-CoV-2 infection enrolled in eleven centres (March 2020 to May 2021). Descriptive analysis of basal characteristics, hospitalization, mortality, and severe clinical course was performed. Comparisons to a population-based control group were made., Results: Forty-one patients were identified. Most patients had wild-type transthyretin CA (61%) and were on NYHA Class II-III (80.5%). CA patients were commonly hospitalized (73.2%) and those were more symptomatic than outpatients (p=0.035). The 24.4% of CA patients died as consequence of SARS-CoV-2 infection. Patients with CA had an increased risk of hospitalization [OR 6.23 (3.05-12.74), p<0.001] and mortality [OR 2.18 (1.01-4.68), p=0.047] when compared to control population after adjustment by age and sex. After a medium follow-time of 311 days, 41.5% of the CA cohort died., Conclusions: SARS-CoV-2 infection is associated with high mortality and hospitalization rates in patients with CA, which exceed that expected by their sex and advanced age., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

We aimed to assess changes in the composition of the waiting list for liver transplantation (LT) after expanding from Milan to "up-to-seven" criteria in patients with hepatocellular carcinoma (HCC). A consecutive cohort of 255 LT candidates was stratified in a pre-expansion era (2016-2018; n = 149) and a post-expansion era (2019-2021; n = 106). The most frequent indication for LT was HCC in both groups (47.7% vs. 43.4%; p = 0.5). The proportion of patients exceeding the Milan criteria in the explanted liver was nearly doubled after expansion (12.5% vs. 21.1%; p = 0.25). Expanding criteria had no effect in drop-out (12.3% vs. 20.4%; p = 0.23) or microvascular invasion rates (37.8% vs. 38.7%; p = 0.93). The length on the waiting list did not increase after the expansion (172 days [IQR 74-282] vs. 118 days [IQR 67-251]; p = 0.135) and was even shortened in the post-expansion HCC subcohort (181 days [IQR 125-232] vs. 116 days [IQR 74-224]; p = 0.04). Tumor recurrence rates were reduced in the post-expansion cohort (15.4% vs. 0%; p = 0.012). In conclusion, expanding from Milan to up-to-seven criteria for LT in patients with HCC had no meaningful impact on the waiting list length and composition, thus offering the opportunity for the adoption of more liberal policies in the future.

Background: Microscopy continues to be the mainstay for the evaluation of parasitaemia in malaria but requires laboratory support and microbiological experience. Other fast and simple methods are necessary., Methods: A retrospective observational study of imported malaria treated from July-2007 to December-2020 was carried out to evaluate the association between the degree of parasitaemia and both rapid diagnostic tests (RDT) reactivity patterns and haematological parameters. Plasmodium falciparum monoinfections diagnosed by peripheral blood smear and/or polymerase chain reaction (PCR),which also had a positive RDT result in the same blood sample, were included in the study., Results: A total of 273 patients were included. Most of them were male (n = 256; 93.8%) and visiting friends and relatives (VFR) travellers (n = 252; 92.3%). Patients with plasmodial lactate dehydrogenase (pLDH) or aldolase and histidine-rich protein 2 (HRP-2) co-reactivity (Pan/Pf pattern) had a parasitaemia range between 0 and 37% while those with just HRP-2 reactivity (P. falciparum pattern) had ranges between 0 and 1%. Not a single case of P. falciparum pattern was found for parasitaemia ranges greater than 1%, showing a negative predictive value of 100% for high parasitaemia. All the correlations between haematological parameters and parasitaemia resulted to be weak, with a maximum rho coefficient of -0.35 for lymphocytes and platelets, and of 0.40 for neutrophils-to-lymphocytes count ratio. Multivariate predictive models were constructed reflecting a poor predictive capacity., Conclusions: The reactivity pattern of RDT allows a rapid semi-quantitative assessment of P. falciparum parasitaemia in travellers with imported malaria, discriminating patients with lower parasite loads. Haematological parameters were not able to estimate parasitaemia with sufficient precision., (© 2023. The Author(s).)

Understanding human visual behavior within virtual reality environments is crucial to fully leverage their potential. While previous research has provided rich visual data from human observers, existing gaze datasets often suffer from the absence of multimodal stimuli. Moreover, no dataset has yet gathered eye gaze trajectories (i.e., scanpaths) for dynamic content with directional ambisonic sound, which is a critical aspect of sound perception by humans. To address this gap, we introduce D-SAV360, a dataset of 4,609 head and eye scanpaths for 360° videos with first-order ambisonics. This dataset enables a more comprehensive study of multimodal interaction on visual behavior in virtual reality environments. We analyze our collected scanpaths from a total of 87 participants viewing 85 different videos and show that various factors such as viewing mode, content type, and gender significantly impact eye movement statistics. We demonstrate the potential of D-SAV360 as a benchmarking resource for state-of-the-art attention prediction models and discuss its possible applications in further research. By providing a comprehensive dataset of eye movement data for dynamic, multimodal virtual environments, our work can facilitate future investigations of visual behavior and attention in virtual reality.

Visual behavior depends on both bottom-up mechanisms, where gaze is driven by the visual conspicuity of the stimuli, and top-down mechanisms, guiding attention towards relevant areas based on the task or goal of the viewer. While this is well-known, visual attention models often focus on bottom-up mechanisms. Existing works have analyzed the effect of high-level cognitive tasks like memory or visual search on visual behavior; however, they have often done so with different stimuli, methodology, metrics and participants, which makes drawing conclusions and comparisons between tasks particularly difficult. In this work we present a systematic study of how different cognitive tasks affect visual behavior in a novel within-subjects design scheme. Participants performed free exploration, memory and visual search tasks in three different scenes while their eye and head movements were being recorded. We found significant, consistent differences between tasks in the distributions of fixations, saccades and head movements. Our findings can provide insights for practitioners and content creators designing task-oriented immersive applications.

Introduction: Transvaginal radiofrequency ablation is a relatively noninvasive approach for the treatment of fibroids in patients who do not wish to undergo conventional surgery. Information on potential complications of this novel technique is very scarce., Methods: Retrospective, descriptive, epidemiological study of 115 patients who underwent transvaginal radiofrequency ablation of fibroids and for whom complications were recorded., Results: We performed 115 transvaginal radiofrequency ablation procedures, we recorded a total of 11 complications (9.6%; 95% CI, 3.8-14.8). Of these, 8 (7.0%) were classified as Clavien-Dindo type I, 1 (0.9%,) as type II, and 2 (1.7%) as type IIIb (severe). No other complications were recorded in a year follow-up., Conclusion: Transvaginal radiofrequency ablation is a treatment option that makes it possible to treat fibroids that are difficult to manage using other techniques. Few associated complications have been described, and most of them are mild., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (© 2023 The Authors.)

Injuries to the dentofacial region caused by third parties can affect physiological, sensory and esthetic functions with legal repercussions. The personal and social circumstances generated by Covid-19 and the governmental measures taken to control it, have increased the risk factors for violence and with it, the resulting injury rate. The aim of the present investigation was to compare the amount of civil liability for dental injury crimes agreed by Spanish courts, in certain Autonomous Communities, before and during the pandemic situation caused by Covid-19. For this purpose, a analytic cross-sectional study was carried out by analyzing sentences from the database of the Judicial Documentation Center. A comparison of means (one-way ANOVA) was used on the amount of compensation between the different years, and between the Autonomous Communities of Madrid, Catalonia Cataluña, Andalusia, the Canary Islands and the Valencian Community. It was observed that the year 2020 stood out for the increase in the number of cases of dental injury offenses. For its part, the Autonomous Community of Andalusia showed the highest amount of compensation during the pandemic, although the highest number of cases corresponded to the Community of Madrid. The statistical analysis yielded a probability of more than 0.05, which eliminated the possibility of significant differences in each of the comparisons., (© 2023. Springer Nature Limited.)

Background: The incidence of postoperative residual curarisation remains unacceptably high. We assessed whether an educational intervention on perioperative neuromuscular block management can reduce it., Methods: In this multicentre, cluster randomised crossover trial, centres were allocated to receive an educational intervention either in a first or a second period. The educational intervention consisted of a lecture about neuromuscular management key points, including quantitative neuromuscular monitoring and use of reversal agents. The lecture was streamed to allow repetition. Additionally, memory cards were distributed in each operating theatre. The primary outcome was postoperative residual curarisation in the PACU. Secondary outcomes were frequency of quantitative neuromuscular monitoring, use of reversal agents, and incidence of postoperative pulmonary complications during hospital stay. Measurements were performed before randomisation and after the first and the second period. The effect of the educational intervention was estimated using multivariable mixed effects logistic regression models., Results: We included 2314 subjects in 34 Spanish centres. Postoperative residual curarisation incidence was not affected by the educational intervention (odds ratio [OR] 0.90 [95% confidence interval {CI}: 0.51-1.58]; P=0.717 and 1.30 [0.73-2.30]; P=0.371] for first and second time-period interaction). The educational intervention increased the quantitative neuromuscular monitor usage (OR 2.04 [95% CI: 1.31-3.19]; P=0.002), the use of reversal agents was unchanged (OR 0.79 [95% CI: 0.50-1.26]; P=0.322), and the incidence of postoperative pulmonary complications decreased (OR 0.19 [95% CI: 0.10-0.35]; P<0.001)., Conclusions: An educational intervention on perioperative neuromuscular block management did not reduce the incidence of postoperative residual curarisation nor increase reversal, despite increased quantitative neuromuscular monitoring. Sugammadex reversal was associated with reduced postoperative residual curarisation. The educational intervention was associated with a decrease in postoperative pulmonary complications., Clinical Trial Registration: NCT03128151., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

The activity of neuronal Kv7.2/Kv7.3 channels is critically dependent on PIP 2 and finely modulated by cholesterol. Here, we report the crosstalk between cholesterol and PIP 2 in the regulation of Kv7.2/Kv7.3 channels. Our results show that currents passing through Kv7.2/Kv7.3 channels in cholesterol-depleted cells, by acute application of methyl-β-cyclodextrin (MβCD), were less sensitive to PIP 2 dephosphorylation strategies than those of control cells, suggesting that cholesterol depletion enhances the Kv7.2/Kv7.3-PIP 2 interaction. In contrast, the sensitivity of Kv7.2/Kv7.3 channels to acute membrane cholesterol depletion by MβCD was not altered in mutant channels with different apparent affinities for PIP 2 ., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: Congenital hypothyroidism (CH) is a decrease in thyroid hormone function in newborns, being one of the leading causes of neurological deficits and long-term metabolic complications. This study aims to determine the prevalence and characteristics of CH cases in Bogotá, Colombia, between 2015 and 2021, as notified through the mandatory report to the Public Health Surveillance System (PHSS)., Methods: A retrospective cross-sectional study was conducted. All live births (LB) with a weight ≥500 g, diagnosed with CH with or without goiter (ICD-10 codes E030 and E031, respectively) in Bogotá during 2015-2021 were analyzed., Results: For a total of 201 cases, the prevalence rate was 3.29 cases per 10,000 LB. 92.54 % were classified as isolated cases of CH, 4.48 % syndromic, and 2.98 % polymalformated. A total of 16.92 % was small for gestational age. The mean gestational age was 37.38 weeks (SD 2.76), 26.87 % were preterm births. Among the mothers, 8.96 % suffered from pregnancy-related or chronic diseases, the most common being hypertensive disorders of pregnancy and pre-existant hypothyroidism (without clarity concerning etiology). A total of 66.67 % of cases did not receive treatment after diagnosis. Treatment was established by an average age of 27 days after birth (SD 36.02) and 17 days after case notification to the PHSS (SD 36.13)., Conclusions: Observed prevalence is similar to the rate reported by health authorities in Colombia but inferior to reports from high-income countries, highlighting the importance of improvements in the Colombian LB's screening program. Time to diagnosis and treatment was observed to be prolonged, suggesting that new pathways are required for timely CH treatment., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

The United States Department of Agriculture defines food insecurity (FI) as reduced quality and variety of diet or overall reduced food intake. To date, limited research has investigated the relationship between FI, weight stigma, and bariatric surgery. The existing literature suggests that FI in bariatric surgery patients is significantly associated with being a person of color, depression, receiving Medicare or Medicaid, and higher eating disorder (ED) pathology. Research also suggests that weight stigma in bariatric surgery patients is associated with worsened weight loss outcomes. No research to our knowledge has investigated FI, internalized weight stigma, weight-based discrimination, and history of bariatric surgery in one sample. Bariatric surgery patients in this study (N = 266) reported elevated rates of FI relative to the general population, via an online questionnaire. Those with FI also reported higher rates of depression, anxiety, ED pathology, internalized weight stigma, and experiences of weight-based discrimination compared to those who were food secure. Given these findings, bariatric surgical centers should evaluate all potential patients for FI before surgery and, at the bare minimum, provide additional support before and post-surgery. The ethics of conducting bariatric surgery in those with FI who lack significant medical comorbidity also must be considered., Competing Interests: Competing interests The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aryl-alcohol oxidases (AAOs) are members of the glucose-methanol-choline oxidase/dehydrogenase (GMC) superfamily. These extracellular flavoproteins have been described as auxiliary enzymes in the degradation of lignin by several white-rot basidiomycetes. In this context, they oxidize fungal secondary metabolites and lignin-derived compounds using O 2 as an electron acceptor, and supply H 2 O 2 to ligninolytic peroxidases. Their substrate specificity, including mechanistic aspects of the oxidation reaction, has been characterized in Pleurotus eryngii AAO, taken as a model enzyme of this GMC superfamily. AAOs show broad reducing-substrate specificity in agreement with their role in lignin degradation, being able to oxidize both nonphenolic and phenolic aryl alcohols (and hydrated aldehydes). In the present work, the AAOs from Pleurotus ostreatus and Bjerkandera adusta were heterologously expressed in Escherichia coli, and their physicochemical properties and oxidizing abilities were compared with those of the well-known recombinant AAO from P. eryngii. In addition, electron acceptors different from O 2 , such as p -benzoquinone and the artificial redox dye 2,6-Dichlorophenolindophenol, were also studied. Differences in reducing-substrate specificity were found between the AAO enzymes from B. adusta and the two Pleurotus species. Moreover, the three AAOs oxidized aryl alcohols concomitantly with the reduction of p -benzoquinone, with similar or even higher efficiencies than when using their preferred oxidizing-substrate, O 2 . IMPORTANCE In this work, quinone reductase activity is analyzed in three AAO flavooxidases, whose preferred oxidizing-substrate is O 2 . The results presented, including reactions in the presence of both oxidizing substrates-benzoquinone and molecular oxygen-suggest that such aryl-alcohol dehydrogenase activity, although less important than its oxidase activity in terms of maximal turnover, may have a physiological role during fungal decay of lignocellulose by the reduction of quinones (and phenoxy radicals) from lignin degradation, preventing repolymerization. Moreover, the resulting hydroquinones would participate in redox-cycling reactions for the production of hydroxyl free radical involved in the oxidative attack of the plant cell-wall. Hydroquinones can also act as mediators for laccases and peroxidases in lignin degradation in the form of semiquinone radicals, as well as activators of lytic polysaccharide monooxygenases in the attack of crystalline cellulose. Moreover, reduction of these, and other phenoxy radicals produced by laccases and peroxidases, promotes lignin degradation by limiting repolymerization reactions. These findings expand the role of AAO in lignin biodegradation., Competing Interests: The authors declare no conflict of interest.

Adipocyte dysfunction is the driver of obesity and correlates with insulin resistance and the onset of type 2 diabetes. Protein kinase N1 (PKN1) is a serine/threonine kinase that has been shown to contribute to Glut4 translocation to the membrane and glucose transport. Here, we evaluated the role of PKN1 in glucose metabolism under insulin-resistant conditions in primary visceral adipose tissue (VAT) from 31 patients with obesity and in murine 3T3-L1 adipocytes. In addition, in vitro studies in human VAT samples and mouse adipocytes were conducted to investigate the role of PKN1 in the adipogenic maturation process and glucose homeostasis control. We show that insulin-resistant adipocytes present a decrease in PKN1 activation levels compared to nondiabetic control counterparts. We further show that PKN1 controls the adipogenesis process and glucose metabolism. PKN1-silenced adipocytes present a decrease in both differentiation process and glucose uptake, with a concomitant decrease in the expression levels of adipogenic markers, such as PPARγ, FABP4, adiponectin and CEBPα. Altogether, these results point to PKN1 as a regulator of key signaling pathways involved in adipocyte differentiation and as an emerging player of adipocyte insulin responsiveness. These findings may provide new therapeutic approaches for the management of insulin resistance in type 2 diabetes.

Background: In high-income countries, hope facilitates parental coping and builds the clinical relationship between families of children with cancer and their clinicians. However, the manifestation of hope in low- and middle-income countries (LMICs) remains poorly understood. Our study explores Guatemalan parents' experiences with hope during the pediatric oncology diagnostic process and aims to identify discrete actions clinicians take to support hope., Methods: This qualitative study utilized audio-recordings of the diagnostic process and an additional semi-structured interview for 20 families of children with cancer at Unidad Nacional de Oncología Pediátrica in Guatemala. Spanish audio-recordings were translated into English, transcribed, and coded using a priori and novel codes. Thematic content analysis using constant comparative methods explored parents' hopes and concerns., Results: At diagnosis, Guatemalan parents expressed both hopes and concerns related to the entire cancer continuum. Throughout the diagnostic process, hope grew as concerns were alleviated. Clinicians supported hope by creating a supportive environment, providing information, affirming religious beliefs, and empowering parents. These strategies helped parents shift their focus from fear and uncertainty toward hope for their child's future. Parents expressed that establishing hope improved mood, promoted acceptance, and enabled them to care for themselves and their children., Conclusion: These results confirm the relevance of supporting hope in pediatric oncology settings in LMICs and suggest that culture informs hope-related needs. Supporting hope is critical across cultures and can be integrated into clinical conversation using the four processes identified by our results., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Lentinula is a broadly distributed group of fungi that contains the cultivated shiitake mushroom, L. edodes . We sequenced 24 genomes representing eight described species and several unnamed lineages of Lentinula from 15 countries on four continents. Lentinula comprises four major clades that arose in the Oligocene, three in the Americas and one in Asia-Australasia. To expand sampling of shiitake mushrooms, we assembled 60 genomes of L. edodes from China that were previously published as raw Illumina reads and added them to our dataset. Lentinula edodes sensu lato (s. lat.) contains three lineages that may warrant recognition as species, one including a single isolate from Nepal that is the sister group to the rest of L. edodes s. lat., a second with 20 cultivars and 12 wild isolates from China, Japan, Korea, and the Russian Far East, and a third with 28 wild isolates from China, Thailand, and Vietnam. Two additional lineages in China have arisen by hybridization among the second and third groups. Genes encoding cysteine sulfoxide lyase ( lecsl ) and γ-glutamyl transpeptidase ( leggt ), which are implicated in biosynthesis of the organosulfur flavor compound lenthionine, have diversified in Lentinula . Paralogs of both genes that are unique to Lentinula ( lecsl 3 and leggt 5b) are coordinately up-regulated in fruiting bodies of L. edodes . The pangenome of L. edodes s. lat. contains 20,308 groups of orthologous genes, but only 6,438 orthogroups (32%) are shared among all strains, whereas 3,444 orthogroups (17%) are found only in wild populations, which should be targeted for conservation.

Schistosomiasis is a neglected tropical disease despite of being a major public health problem affecting nearly 240 million people in the world. Due to the migratory flow from endemic countries to Western countries, an increasing number of cases is being diagnosed in non-endemic areas, generally in migrants or people visiting these areas. Serology is the recommended method for screening and diagnosis of schistosomiasis in migrants from endemic regions. However, serological techniques have a highly variable sensitivity. The aim of this study was to evaluate retrospectively the sensitivity of three different serological tests used in real clinical practice for the screening and diagnosis of imported schistosomiasis in sub-Saharan migrant patients, using the detection of schistosome eggs in urine, faeces or tissues as the gold standard. We evaluated three different serological techniques in 405 sub-Saharan patients with confirmed schistosomiasis treated between 2004 and 2022: an enzyme-linked immunosorbent assay (ELISA), an indirect haemagglutination assay (IHA) and an immunochromatographic test (ICT). The overall sensitivity values obtained with the different techniques were: 44.4% for IHA, 71.2% for ELISA and 94.7% for ICT, respectively. According to species, ICT showed the highest sensitivity ( S. haematobium : 94%, S. mansoni : 93.3%; and S. intercalatum / guineensis : 100%). In conclusion, our study shows that Schistosoma ICT has the best performance in real clinical practice, when compared to ELISA and IHA, in both S. mansoni and S. haematobium infections.

Objective: To explore the experiences of people with persistent COVID in the Basque Country more than a year after the start of the pandemic, in order to understand the health and social impact it has, as well as to detect possible areas for improvement in the care that these people receive in order to develop health programms to support their recovery., Method: Qualitative phenomenological study. In-depth interviews will be carried out as a data collection technique until saturation of the discourse. Patients of legal age who present persistent COVID symptomatology with an evolution time of more than 12 weeks were included. Contact with the patients was made through the Basque Long COVID Collective. The interviews were carried out and recorded through the ZOOM application. After the literal transcription of the interviews, the thematic analysis will be carried out, identifying the first units of meaning and assigning codes that will later be grouped into the different categories., Results: 20 patients participated. A total of three main categories emerged from the analysis of the discourses: 1) affecting/impacting patients' quality of life; 2) identifying improvements in healthcare; and 3) comforting aspects., Conclusions: This study shows the significant impact on the quality of life suffered by these people. It is necessary to design health policies that favour a personalised, comprehensive and multidisciplinary approach to these patients., (Copyright © 2022 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

The use of virtual worlds in health-related education is increasingly popular, but an overview of their use in physiotherapy education is still needed. The aim of this review was to analyse the use of virtual and augmented reality (VR/AR) compared to traditional methods for teaching physiotherapy. A systematic review was performed up to October 2022 in PubMed, Web of Science, Scopus, CINAHL, and PsycInfo. The quality appraisal and risk of bias were assessed by the Joana Briggs Institute checklist and the Cochrane Collaboration's RoB Tool 2.0, respectively. A total of seven randomised and non-randomised controlled studies were included, involving 737 students. VR/AR-based teaching approaches included simulation and virtual worlds, and were conducted through immersive head-mounted displays, AR-based applications, and 3D visualisations. Three studies were focused on teaching anatomy content, two on clinical decision making skills, and the rest were focused on pathology, physiotherapy tasks or exercise performance, and movement analysis of lower limbs. Inconclusive results were found in terms of learning satisfaction and academic performance, showing VR/AR-based teaching models to be equally effective as traditional methods for teaching physiotherapy. We encourage researchers and teachers to include games in their VR/AR-based teaching approaches to enhance interaction and active learning in physiotherapy education.

Objective: To investigate barriers in accessing care for infertility in Mexico, because little is known about this issue for low and middle-income countries, which comprise 80% of the world's population., Design: Cross-sectional analysis., Setting: Mexcian Teachers' Cohort., Patients: A total of 115,315 female public school teachers from 12 states in Mexico., Interventions: None., Main Outcome Measures: The participants were asked detailed questions about their demographics, lifestyle characteristics, access to the health care system, and infertility history via a self-reported questionnaire. Log-binomial models, adjusted a priori for potential confounding factors, were used to estimate the prevalence ratios (PRs) and 95% confidence intervals ( CIs) of accessing medical care for infertility among women reporting a history of infertility., Results: A total of 19,580 (17%) participants reported a history of infertility. Of those who experienced infertility, 12,470 (63.7%) reported seeking medical care for infertility, among whom 8,467 (67.9%) reported undergoing fertility treatments. Among women who reported a history of infertility, women who taught in a rural school (PR, 0.95; 95% CI, 0.92-0.97), spoke an indigenous language (PR, 0.88; 95% CI, 0.84-0.92), or had less than a university degree (PR, 0.93; 95% CI, 0.90-0.97) were less likely to access medical care for fertility. Women who had ever had a mammogram (PR, 1.07; 95% CI, 1.05-1.10), had a pap smear in the past year (PR, 1.08; 95% CI, 1.06-1.10), or who had used private health care regularly or in times of illness were more likely to access medical care for fertility., Conclusions: The usage of infertility care varied by demographic, lifestyle, and access characteristics, including speaking an indigenous language, teaching in a rural school, and having a private health care provider., (© 2022 The Authors.)

This registered report introduces the largest, and for the first time, reproducible experimental survey on biomedical sentence similarity with the following aims: (1) to elucidate the state of the art of the problem; (2) to solve some reproducibility problems preventing the evaluation of most current methods; (3) to evaluate several unexplored sentence similarity methods; (4) to evaluate for the first time an unexplored benchmark, called Corpus-Transcriptional-Regulation (CTR); (5) to carry out a study on the impact of the pre-processing stages and Named Entity Recognition (NER) tools on the performance of the sentence similarity methods; and finally, (6) to bridge the lack of software and data reproducibility resources for methods and experiments in this line of research. Our reproducible experimental survey is based on a single software platform, which is provided with a detailed reproducibility protocol and dataset as supplementary material to allow the exact replication of all our experiments and results. In addition, we introduce a new aggregated string-based sentence similarity method, called LiBlock, together with eight variants of current ontology-based methods, and a new pre-trained word embedding model trained on the full-text articles in the PMC-BioC corpus. Our experiments show that our novel string-based measure establishes the new state of the art in sentence similarity analysis in the biomedical domain and significantly outperforms all the methods evaluated herein, with the only exception of one ontology-based method. Likewise, our experiments confirm that the pre-processing stages, and the choice of the NER tool for ontology-based methods, have a very significant impact on the performance of the sentence similarity methods. We also detail some drawbacks and limitations of current methods, and highlight the need to refine the current benchmarks. Finally, a notable finding is that our new string-based method significantly outperforms all state-of-the-art Machine Learning (ML) models evaluated herein., Competing Interests: NO authors have competing interests., (Copyright: © 2022 Lara-Clares et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Phenotypic plasticity is a main mechanism for organisms to cope with changing environments and broaden their ecological range. Plasticity is genetically based and can evolve under natural selection, such that populations within a species show distinct phenotypic responses to the environment if evolved under different conditions. Understanding how intraspecific variation in phenotypic plasticity arises is critical to assess potential adaptation to ongoing climate change. Theory predicts that plasticity is favored in more favorable but variable environments. Yet, many theoretical predictions about benefits, costs, and selection on plasticity remain untested. To test these predictions, we took advantage of three genetic trials in the northern Rocky Mountains, USA, which assessed 23 closely located Pinus ponderosa populations over 27 years. Mean environmental conditions and their spatial patterns of variation at the seed source populations were characterized based on six basic climate parameters. Despite the small area of origin, there was significant genetic variation in phenotypic plasticity for tree growth among populations. We found a significant negative correlation between phenotypic plasticity and the patch size of environmental heterogeneity at the seed source populations, but not with total environmental spatial variance. These results show that populations exposed to high microhabitat heterogeneity have evolved higher phenotypic plasticity and that the trigger was the grain rather than the total magnitude of spatial heterogeneity. Contrary to theoretical predictions, we also found a positive relationship between population plasticity and summer drought at the seed source, indicating that drought can act as a trigger of plasticity. Finally, we found a negative correlation between the quantitative genetic variance within populations and their phenotypic plasticity, suggesting compensatory adaptive mechanisms for the lack of genetic diversity. These results improve our understanding of the microevolutionary drivers of phenotypic plasticity, a critical process for resilience of long-lived species under climate change, and support decision-making in tree genetic improvement programs and seed transfer strategies., Competing Interests: The authors declare that there is no conflict of interest., (© 2022 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Background: Lower eosinophil counts observed during acute malaria episodes could hide helminth-related eosinophilia., Method: Retrospective observational study with sub-Saharan migrants with imported malaria from May-2007 to May-2020. Absolute eosinophil count was determined upon diagnosis at hospital admission and at least once after clearance of parasitemia. Helminthic co-infections were investigated by searching for stool and urine parasites, serology for Strongyloides spp. and Schistosoma spp., and Knott and/or saponin tests for blood microfilariae., Results: A total of 259 patients were included. Most of them were male (n = 237; 91.5%) and VFR travelers (n = 241; 93.1%). 131 patients (50.6%) were diagnosed with probable schistosomiasis, 15 (5.8%) with confirmed schistosomiasis, 16 (6.2%) with strongyloidiasis, 4 (1.6%) with soil-transmitted helminthiasis, and 4 (1.6%) with filariasis (Mansonella perstans). Prevalence of eosinophilia increased from 2.7% on admission to 32.5% during outpatient follow-up. Eosinophilia did not appear until several weeks after hospital discharge in up to 24% of the confirmed helminthic co-infections and in 61.1% of patients with probable schistosomiasis. Eosinophilia was associated with confirmed schistosomiasis and mansonellosis while 56.2% and 75% of cases with strongyloidiasis and soil-transmitted worms did not present eosinophilia at any time, respectively., Conclusions: Regardless of the absence of eosinophilia, patients hospitalized because of acute imported malaria might benefit from the screening of the main parasitic diseases, allowing for earlier diagnosis and treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Superparamagnetic iron nanoparticles (SPIONs) have become one of the most useful colloidal systems in nanomedicine. We report here the preparation of new hybrid core@shell systems based on SPION nanoparticles coated with a SiO 2 shell (SPION@SiO 2 ) and functionalized with carboxyl groups (SPION@SiO 2 -COOH). A series of new N-alkylamino- and N-alkylamido-terminated 1-phenyl- tetrahydroisoquinolines (THIQs) and 3-tetrahydrobenzazepines (THBs) derivatives presenting -SMe and -Cl groups, respectively, with potential dopaminergic activity, are synthesized and incorporated to the hybrid system. We include the synthetic details for THIQs and THBs derivatives preparation and investigate the influence of the terminal-functional group as well as the number of carbon atoms linked to THIQ and THB molecules during the coupling to the SPION@SiO 2 -COOH. Nuclear magnetic resonance (NMR) and electron ionization mass spectrometry (EI-MS) are used to characterize the synthesized THIQs and THBs. High-angle annular dark-field transmission electron microscopy (HAADF-TEM), energy dispersive X-ray transmission electron microscopy (EDX-TEM), and proton high-resolution magic angle spinning NMR spectroscopy 1 H HRMAS-NMR) are used to confirm the presence of THB and THIQ molecules onto the surface of the nanoparticles. The hybrid SPION@SiO 2 -THIQ and THB systems show significant activity toward the D 2 receptor, reaching Ki values of about 20 nM, thus having potential application in the treatment of central nervous system (CNS) diseases., (Copyright © 2022 Elsevier Ltd. All rights reserved.)