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Patients with multiple myeloma (MM) frequently present with kidney involvement, of which a non-negligible proportion will progress to end-stage kidney disease. Kidney transplantation (KT) is the preferred kidney replacement therapy for selected patients; however, there are still many uncertainties regarding its application in MM patients. The risk of hematological relapse and subsequent graft loss or patient death often leads nephrologists to deem these patients unfit for KT. As such, data on KT in MM patients are heterogeneous and originate from individual case reports and small case series. Although MM is still an incurable disease, the addition of newer drugs and autologous hematopoietic stem cell transplant (HSCT) in the standard of care has been increasing patients' overall survival in recent decades. Risk stratification using cytogenetic studies and minimal residual disease detection are helpful in assessing the risk of relapse in patients who attain a complete response after HSCT. The greatest challenges remain the correct identification of patients who will most probably benefit from KT from a survival perspective and the determination of how long relapse-free survival should be before the transplant is performed.

The aim of this paper is to summarize the available evidence in the literature regarding the effects generated by exposure to an enriched environment (EE) on the modulation of epigenetic processes in the central nervous system under adverse environmental conditions. Searches were conducted in three databases: PubMed/Medline (1053 articles), Scopus (121 articles), and Embase (52 articles), which were subjected to eligibility criteria. Of the 1226 articles found, 173 duplicates were removed. After evaluating titles/abstracts, 904 studies were excluded, resulting in 49 articles, of which 14 were included in this systematic review. EE was performed using different inanimate objects. Adverse environmental conditions included CUMS, sepsis, nicotine exposure, PCP exposure, early stress, WAS, high fructose intake, TBI, and sevoflurane exposure. Regarding microRNA expression, after exposure to EE, an increase in the expression of miR-221 and miR-483 was observed in the prefrontal cortex, and a reduction in the expression of miR-92a-3p and miR-134 in the hippocampus. Regarding histone modifications, in the hippocampus, there was a reduction of HAT, HDAC/HDAC4, H3 (acetyl K14), H4 (acetyl K15), H3K4me3, K3k27me3, and HDAC2/3/5. In the cortex, there was a reduction of HDAC2, and in the prefrontal cortex, there was an increase in acetylated H3. Regarding DNA modifications, there was a reduction of DNMT in the hippocampus. This systematic review concludes that the benefits of EE on the brain and behavior of animals are directly related to different epigenetic mechanisms, reflecting in cell growth and neuroplasticity. EE may be a non-pharmacological and easy-to-apply alternative to prevent symptoms in disorders affecting brain tissue., (© 2024. The Author(s).)

Seed dispersal is crucial for ecosystem persistence, especially in fragmented landscapes, such as those common in Europe. Ongoing defaunation might compromise effective seed dispersal, but the conservation status of pairwise interactions remains unknown. With a literature review, we reconstructed the first European-wide seed dispersal network and evaluated the conservation status of interactions by assessing each interacting partner's IUCN (International Union for Conservation of Nature) conservation status and population trends. We found that a third of the disperser species and interactions face potential extinction and that 30% of the plant species have most of their dispersers threatened or declining. Our study reveals a developing seed dispersal crisis in Europe and highlights large knowledge gaps regarding the dispersers and conservation status of zoochorous plants, urging further scrutiny and action to conserve the seed dispersal service.

Abemaciclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor used for hormone-receptor-positive and human epidermal growth factor receptor 2 (HER-2)-negative breast cancer, can lead to elevated serum creatinine without implications on the true renal function. Although clinical trials have shown no increase in other kidney function biomarkers, this may still represent a challenge in cancer patients. We report a case of a 74-year-old female who presented with creatinine and cystatin-C elevation during treatment with abemaciclib without an equivalent decrease in measured glomerular filtration rate (GFR) with renal scintigraphy. The confirmation of adequate kidney function allowed for the maintenance of treatments that would otherwise be limited by renal impairment. Healthcare providers should be aware of abemaciclib's effect on serum creatinine but should not eliminate the possibility of actual kidney injury. Alternative biomarkers for GFR assessment are recommended, although the usefulness of cystatin-C in patients receiving abemaciclib should be investigated in greater depth., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ferreira et al.)

Veterinary palliative care consists of end-of-life care of companion animals suffering from terminal or life-limiting diseases. Despite the growing need for veterinary palliative care, little research has been conducted on this topic. This perspective intends to provide an overview of the existing concerns and identify knowledge gaps to motivate further research. As a result, three main areas of research have been identified, namely: i) how to provide palliative care considering welfare implications of different diseases (e.g., pain management); ii) what can be considered a "good death", depending on the individual situation of the animal and its caregiver; iii) how to support caregivers' needs during their companion animal's end-of-life. Therefore, veterinary palliative care involves medical, ethical, and sociological considerations that should be addressed through guidelines and training., Competing Interests: Declaration of Competing Interest None of the authors of this paper has a financial or personal relationship with other people or organisations that could inappropriately influence or bias the content of the paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Animals can adjust their diet to maximize energy or nutritional intake. For example, birds often target fruits that match their beak size because those fruits can be consumed more efficiently. We hypothesized that pressure to optimize diet-measured as matching between fruit and beak size-increases under stressful environments, such as those that determine species' range edges. Using fruit-consumption and trait information for 97 frugivorous bird and 831 plant species across six continents, we demonstrate that birds feed more frequently on closely size-matched fruits near their geographic range limits. This pattern was particularly strong for highly frugivorous birds, whereas opportunistic frugivores showed no such tendency. These findings highlight how frugivore interactions might respond to stressful conditions and reveal that trait matching may not predict resource use consistently.

Objective: To evaluate the performance of prenatal screening for common autosomal trisomies in twin pregnancies through the use of rolling-circle replication (RCR)-cfDNA as a first-tier test., Method: Prospective multicenter study. Women who underwent prenatal screening for trisomy (T) 21, 18 and 13 between January 2019 and March 2022 in twin pregnancies were included. Patients were included in two centers. The primary endpoint was the rate of no-call results in women who received prenatal screening for common autosomal trisomies by RCR-cfDNA at the first attempt, compared to that in prospectively collected samples from 16,382 singleton pregnancies. The secondary endpoints were the performance indices of the RCR-cfDNA., Results: 862 twin pregnancies underwent screening for T21, T18 and T13 by RCR-cfDNA testing at 10-33 weeks' gestation. The RCR-cfDNA tests provided a no-call result from the first sample obtained from the patients in 107 (0.7%) singleton and 17 (2.0%) twin pregnancies. Multivariable regression analysis demonstrated that significant independent predictors of test failure were twin pregnancy and in vitro fertilization conception. All cases of T21 (n = 20/862; 2.3%), T18 (n = 4/862; 0.5%) and T13 (n = 1/862; 0.1%) were correctly detected by RCR-cfDNA (respectively, 20, 4 and 1 cases). Sensitivity was 100% (95% CI, 83.1%-100%), 100% (95% CI 39.8%-100%) and 100% (95% CI 2.5%-100%) for T21, T18 and T13, respectively, in twin pregnancies., Conclusion: The RCR-cfDNA test appears to have good accuracy with a low rate of no-call results in a cohort of twin pregnancies for the detection of the most frequent autosomal trisomies., (© 2024 The Author(s). Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Background: Though maternal diabetes effects are well described in the literature, the effects of maternal diabetes in postnatal phases are often overlooked. Diabetic individuals have higher levels of circulating glycotoxins, and there is a positive correlation between maternal-derived glycotoxins and circulating glycotoxins in their progeny. Previous studies evaluated the metabolic effects of high glycotoxin exposure during lactation in adult animals. However, here we focus on the cardiovascular system of juvenile rats., Methods: For this, we used two experimental models: 1. High Methylglyoxal (MG) environment: pregnant Wistar rats were injected with PBS (VEH group) or Methylglyoxal (MG group; 60 mg/kg/day; orally, postnatal day (PND) 3 to PND14). 2. GLO-1 inhibition: pregnant Wistar rats were injected with dimethyl sulfoxide (VEH group) or a GLO-1 inhibitor (BBGC group; 5 mg/kg/day; subcutaneously, PND1-PND5). The offspring were evaluated at PND45., Results: MG offspring presented cardiac dysfunction and subtly worsened vasomotor responses in the presence of perivascular adipose tissue, without morphological alterations. In addition, an endogenous increase in maternal glycotoxins impacts offspring vasomotricity due to impaired redox status., Conclusions: Our data suggest that early glycotoxin exposure led to cardiac and vascular impairments, which may increase the risk for developing cardiovascular diseases later in life.

Species phenology - the timing of key life events - is being altered by ongoing climate changes with yet underappreciated consequences for ecosystem stability. While flowering is generally occurring earlier, we know much less about other key processes such as the time of fruit ripening, largely due to the lack of comprehensive long-term datasets. Here we provide information on the exact date and site where seeds of 4,462 taxa were collected for the Index Seminum (seed exchange catalogue) of the Botanic Garden of the University of Coimbra, between 1926 and 2013. Seeds were collected from spontaneous and cultivated individuals across Portugal, including both native and introduced taxa. The database consists of 127,747 curated records with information on the species, or infraspecific taxa (including authority), and the day and site where seeds were collected. All records are georeferenced and provided with a confidence interval for the collection site. Taxonomy was first curated manually by in-house botanists and then harmonized according to the GBIF backbone taxonomy., (© 2024. The Author(s).)

Global water demand and environmental concerns related to climate change require industries to develop high-efficiency wastewater treatment methods to remove pollutants. Likewise, toxic pollutants present in wastewater negatively affect the environment and human health, requiring effective treatment. Although conventional treatment processes remove carbon and nutrients, they are insufficient to remove pharmaceuticals, pesticides, and plasticizers. Electrochemical processes effectively remove pollutants from wastewater through the mineralization of non-biodegradable pollutants with consequent conversion into biodegradable compounds. Its advantages include easy operation, versatility, and short reaction time. In this way, this review initially provides a global water scenario with a view to the future. It comprises global demand, treatment methods, and pollution of water resources, addressing various contaminants such as heavy metals, nutrients, organic compounds, and emerging contaminants. Subsequently, the fundamentals of electrochemical treatments are presented as well as electrochemical treatments, highlighting the latest studies involving electrocoagulation, electroflocculation, electroflotation, capacitive deionization and its derivatives, eletrodeionization, and electrochemical advanced oxidation process. Finally, the challenges and perspectives were discussed. In this context, electrochemical processes have proven promising and effective for the treatment of water and wastewater, allowing safe reuse practices and purification with high contaminant removal., 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 Ltd. All rights reserved.)

Purpose: This study evaluates expert opinion on laryngeal electromyography (LEMG)., Methods: A cross-sectional design was used to conduct an online survey of LEMG experts in 2021. They were questioned about the number LEMG performed annually, type of electrodes used, sector worked in, pain during the test, placement of the needle electrodes, interpretation of electrical muscle parameters, diagnosis of neuromuscular injury, prognostic sensitivity in vocal fold paralysis (VFP), laryngeal dystonia, tremor and synkinesis and quantifying LEMG., Results: Thirty-seven professionals answered (23 Spanish and 14 from other countries), with a response rate of 21.56%. All physicians used LEMG. 91.9% had one- or two-years' experience and 56.8% performed 10-40 LEMG per year. 70.3% were otolaryngologists and 27%, neurologists. In 89.1% of cases, a team of electrodiagnostic physician and otolaryngologist performed LEMG. 91.3% of Spanish respondents worked in Public Health, 7.14% of other nationalities; 37.8% in a university department. Bipolar concentric needles electrodes were used by 45.9% and monopolar concentric by 40.5%. 57% professionals considered good patients' tolerance to the test. LEMG sensitivity was regarded as strong, median and interquartile range were 80.0 [60.0;90.0] to diagnose peripheral nerve injuries, less for other levels of lesions, and strong to evaluate prognosis, 70.0 [50.0;80.0]. Respondents believe locate the thyroarytenoid and the cricothyroid muscles with the needle, 80.0 [70.0;90.0], as opposed to 20.0 [0.00;60.0] the posterior cricoarytenoid. The interpretation of the electrical parts of the LEMG was strong, 80.0 [60.0;90.0]. LEMG identify movements disorders, 60.0 [20.0;80.0], and synkinesis, 70.0 [30.0;80.0]. The professionals prefer quantitative LEMG, 90.0 [60.0;90.0]., Conclusions: The experts surveyed consider LEMG that is well tolerated by patients. The insertional and spontaneous activity, recruitment and waveform morphology can be assessed easily. LEMG is mainly useful in the study of peripheral nerve injuries, and its value in VFP prognosis is considered strong., (Copyright © 2023 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: In singleton pregnancies, the use of cell-free DNA (cfDNA) analysis as a screening test for common fetal trisomies has spread worldwide though we still lack sufficient data for its use in triplet pregnancies. The objective of this study is to assess the performance of cfDNA testing in detecting fetal aneuploidies in triplet pregnancies as a first-tier test., Method: We performed a retrospective cohort study including data from pregnant women with a triplet pregnancy who underwent cfDNA testing between May 1, 2017, and January 15, 2020. cfDNA was obtained by massive parallel sequencing (VeriSeq NIPT solution; Illumina®). The objectives of the study were to assess the diagnostic performance of cfDNA testing for trisomy 21 (T21) (primary outcome), trisomy 18 (T18) and 13 (secondary outcomes)., Results: During the study period, cfDNA testing was performed in 255 women with triplet pregnancy, of which 165 (64.7%) had a neonatal outcome available. Three tests were positive for T21, one of which was confirmed by an antenatal karyotype, and the other was confirmed at birth. The third case did not undergo an invasive procedure and was not confirmed at birth (false positive). In one case, cfDNA testing was positive for T18 and was confirmed by an antenatal karyotype. There were no cases of trisomy 13 in the cohort. The no-call rate was 2.4% at first sampling. Fifty-eight (22.7%) women had embryo reduction, which in 40 (69%) of whom was performed after the cfDNA test result., Conclusion: cfDNA testing could be offered as primary screening for main fetal aneuploidies in triplet pregnancies after provision of appropriate patient information., (© 2024 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Purpose: Polycystic ovary syndrome (PCOS) is a common endocrine disorder often linked to metabolic syndrome (MS), raising the risk of cardiovascular disease and type II diabetes. Certain indicators, such as the lipid accumulation product (LAP) and homeostatic model assessment for insulin resistance (HOMA-IR), can predict MS in PCOS patients. This study aimed to assess the predictive power of the visceral adiposity index (VAI) in comparison to LAP and HOMA-IR as predictors of MS in PCOS patients., Methods: In this cross-sectional observational study, data from 317 diagnosed PCOS women were analyzed. VAI, LAP, and HOMA-IR were computed as indexes. Participants were categorized into two groups for index accuracy comparison: PCOS patients with and without MS. The data were assessed using a ROC curve., Results: Among PCOS women with MS, 92.3% had abnormal VAI results, 94.5% had abnormal LAP results, and only 50.5% had abnormal HOMA-IR results. Conversely, the majority of PCOS women without MS had normal HOMA-IR (64.6%). When comparing these indexes using the ROC curve, VAI displayed the highest accuracy, followed by LAP and HOMA-IR., Conclusion: The VAI index proved to be a superior predictor of metabolic MS in PCOS women when compared to other indexes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Steroid myopathy is a clinically challenging condition exacerbated by prolonged corticosteroid use or adrenal tumors. In this study, we engineered a functional three-dimensional (3D) in vitro skeletal muscle model to investigate steroid myopathy. By subjecting our bioengineered muscle tissues to dexamethasone treatment, we reproduced the molecular and functional aspects of this disease. Dexamethasone caused a substantial reduction in muscle force, myotube diameter and induced fatigue. We observed nuclear translocation of the glucocorticoid receptor (GCR) and activation of the ubiquitin-proteasome system within our model, suggesting their coordinated role in muscle atrophy. We then examined the therapeutic potential of taurine in our 3D model for steroid myopathy. Our findings revealed an upregulation of phosphorylated AKT by taurine, effectively countering the hyperactivation of the ubiquitin-proteasomal pathway. Importantly, we demonstrate that discontinuing corticosteroid treatment was insufficient to restore muscle mass and function. Taurine treatment, when administered concurrently with corticosteroids, notably enhanced contractile strength and protein turnover by upregulating the AKT-mTOR axis. Our model not only identifies a promising therapeutic target, but also suggests combinatorial treatment that may benefit individuals undergoing corticosteroid treatment or those diagnosed with adrenal tumors., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

In Portugal, the number of fires and the size of burnt areas are rising dramatically every year, increasing with improper management of agroforestry wastes (AFRs). This work aims to study the composting of these wastes with minimal operational costs and understand the environmental impact and the compost application on burnt soil. Thus, a study of life cycle assessment (LCA) was carried out based on windrow composting processes, considering the avoided environmental impacts associated with the end-product quality and its application as an organic amendment. Three composting piles were made with AFRs from the Residual Biomass Collection Centre (RBCC) in Bodiosa (Portugal). Sewage sludges (SS) from an urban wastewater treatment plant were used as conditioning agent. One pile with AFRs (MC) and another with AFRs and SS (MCS) were managed according to good composting practices. Another pile with the AFRs was developed without management (NMC), thus with a minimal operational cost. Periodically, it was measured several physical and chemical parameters according to standard methodologies. Eleven environmental impacts of compost production, MC and MCS, were analyzed by a LCA tool, and their effect on the growth of Pinus pinea was evaluated, using peat as reference. Composting evolution was expected for both piles. Final composts, MC and MCS, were similar, complying with organic amendment quality parameters. Compost NMC, with no operational management, showed the highest germination index. Piles MC and MCS showed similar environmental impacts, contributing to a negative impact on global warming, acidification, and eutrophication. Greater growth was obtained with application of MCS, followed by MC, and finally, peat. Composting is a sustainable way to valorize AFRs wastes, producing compost that could restore burnt soils and promote plant growth and circular economy., (© 2024. The Author(s).)

Background: Acute kidney injury (AKI) is a common complication among cancer patients, often leading to longer hospital stays, discontinuation of cancer treatment, and a poor prognosis. This study aims to provide insight into the incidence of severe AKI in this population and identify the risk factors associated with renal replacement therapy (RRT) and in-hospital mortality., Methods: This retrospective cohort study included 3201 patients with cancer and severe AKI admitted to a Comprehensive Cancer Center between January 1995 and July 2023. Severe AKI was defined according to the KDIGO guidelines as grade ≥ 2 AKI with nephrological in-hospital follow-up. Data were analyzed in two timelines: Period A (1995-2010) and Period B (2011-2023)., Results: A total of 3201 patients (1% of all hospitalized cases) were included, with a mean age of 62.5 ± 17.2 years. Solid tumors represented 75% of all neoplasms, showing an increasing tendency, while hematological cancer decreased. Obstructive AKI declined, whereas the incidence of sepsis-associated, prerenal, and drug-induced AKI increased. Overall, 20% of patients required RRT, and 26.4% died during hospitalization. A predictive model for RRT (AUC 0.833 [95% CI 0.817-0.848]) identified sepsis and hematological cancer as risk factors and prerenal and obstructive AKI as protective factors. A similar model for overall in-hospital mortality (AUC 0.731 [95% CI 0.71-0.752]) revealed invasive mechanical ventilation (IMV), sepsis, and RRT as risk factors and obstructive AKI as a protective factor. The model for hemato-oncological patients' mortality (AUC 0.832 [95% CI 0.803-0.861]) included IMV, sepsis, hematopoietic stem cell transplantation, and drug-induced AKI. Mortality risk point score models were derived from these analyses., Conclusions: This study addresses the demographic and clinical features of cancer patients with severe AKI. The development of predictive models for RRT and in-hospital mortality, along with risk point scores, may play a role in the management of this population.

Fused filament fabrication (FFF) is an extrusion-based additive manufacturing (AM) technology mostly used to produce thermoplastic parts. However, producing metallic or ceramic parts by FFF is also a sintered-based AM process. FFF for metallic parts can be divided into five steps: (1) raw material selection and feedstock mixture (including palletization), (2) filament production (extrusion), (3) production of AM components using the filament extrusion process, (4) debinding, and (5) sintering. These steps are interrelated, where the parameters interact with the others and have a key role in the integrity and quality of the final metallic parts. FFF can produce high-accuracy and complex metallic parts, potentially revolutionizing the manufacturing industry and taking AM components to a new level. In the FFF technology for metallic materials, material compatibility, production quality, and cost-effectiveness are the challenges to overcome to make it more competitive compared to other AM technologies, like the laser processes. This review provides a comprehensive overview of the recent developments in FFF for metallic materials, including the metals and binders used, the challenges faced, potential applications, and the impact of FFF on the manufacturing (prototyping and end parts), design freedom, customization, sustainability, supply chain, among others.

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is associated with ACADM gene mutations, leading to an impaired function and/or structure of MCAD. Importantly, after import into the mitochondria, MCAD must incorporate a molecule of flavin adenine dinucleotide (FAD) per subunit and assemble into tetramers. However, the effect of MCAD amino acid substitutions on FAD incorporation has not been investigated. Herein, the commonest MCAD variant (p.K304E) and 11 additional rare variants (p.Y48C, p.R55G, p.A88P, p.Y133C, p.A140T, p.D143V, p.G224R, p.L238F, p.V264I, p.Y372N, and p.G377V) were functionally and structurally characterized. Half of the studied variants presented a FAD content <65 % compared to the wild-type. Most of them were recovered as tetramers, except the p.Y372N (mainly as dimers). No correlation was found between the levels of tetramers and FAD content. However, a correlation between FAD content and the cofactor's affinity, proteolytic stability, thermostability, and thermal inactivation was established. We showed that the studied amino acid changes in MCAD may alter the substrate chain-length dependence and the interaction with electron-transferring-flavoprotein (ETF) necessary for a proper functioning electron transfer thus adding additional layers of complexity to the pathological effect of ACADM missense mutations. Although the majority of the variant MCADs presented an impaired capacity to retain FAD during their synthesis, some of them were structurally rescued by cofactor supplementation, suggesting that in the mitochondrial environment the levels and activity of those variants may be dependent of FAD's availability thus contributing for the heterogeneity of the MCADD phenotype found in patients presenting the same genotype., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

(1) Background: Aspergillus flavus is a cosmopolitan mold with medical, veterinary, and agronomic concerns. Its morphological similarity to other cryptic species of the Flavi section requires molecular identification techniques that are not routinely performed. For clinical isolates of Aspergillus section Flavi , we present the molecular identification, susceptibility to six antifungal agents, and clinical context of source patients. (2) Methods: One hundred forty fungal clinical isolates were included in the study. These isolates, recovered over a 15-year period (2001-2015), were identified based on their morphological characteristics as belonging to section Flavi . After the subculture, sequencing of a part of the β-tubulin and calmodulin genes was performed, and resistance to azole antifungals was screened on agar plates containing itraconazole and voriconazole. Minimum inhibitory concentrations were determined for 120 isolates by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. (3) Results: Partial β-tubulin and calmodulin sequences analysis showed that 138/140 isolates were A. flavus sensu stricto , 1 isolate was A. parasiticus/sojae, and 1 was A. nomiae . Many of the isolates came from samples collected in the context of respiratory tract colonization. Among probable or proven aspergillosis, respiratory infections were the most frequent, followed by ENT infections. Antifungal susceptibility testing was available for isolates (n = 120, all A. flavus ss ) from one hospital. The MIC range (geometric mean MIC) in mg/L was 0.5-8 (0.77), 0.5-8 (1.03), 0.125-2 (0.25), 0.03-2 (0.22), 0.25-8 (1.91), and 0.03-0.125 (0.061) for voriconazole, isavuconazole, itraconazole, posaconazole, amphotericin B, and caspofungin, respectively. Two (1.67%) isolates showed resistance to isavuconazole according to current EUCAST breakpoints with MICs at 8 mg/L for isavuconazole and voriconazole. One of these two isolates was also resistant to itraconazole with MIC at 2 mg/L. (4) Conclusions: The present characterization of a large collection of Aspergillus belonging to the Flavi section confirmed that A. flavus ss is the predominant species. It is mainly implicated in respiratory and ENT infections. The emergence of resistance highlights the need to perform susceptibility tests on section Flavi isolates.

Duchenne muscular dystrophy (DMD) is the most prevalent neuromuscular disease diagnosed in childhood. It is a progressive and wasting disease, characterized by a degeneration of skeletal and cardiac muscles caused by the lack of dystrophin protein. The absence of this crucial structural protein leads to sarcolemmal fragility, resulting in muscle fiber damage during contraction. Despite ongoing efforts, there is no cure available for DMD patients. One of the primary challenges is the limited efficacy of current preclinical tools, which fail in modeling the biological complexity of the disease. Human-based three-dimensional (3D) cell culture methods appear as a novel approach to accelerate preclinical research by enhancing the reproduction of pathophysiological processes in skeletal muscle. In this work, we developed a patient-derived functional 3D skeletal muscle model of DMD that reproduces the sarcolemmal damage found in the native DMD muscle. These bioengineered skeletal muscle tissues exhibit contractile functionality, as they responded to electrical pulse stimulation. Sustained contractile regimes induced the loss of myotube integrity, mirroring the pathological myotube breakdown inherent in DMD due to sarcolemmal instability. Moreover, damaged DMD tissues showed disease functional phenotypes, such as tetanic fatigue. We also evaluated the therapeutic effect of utrophin upregulator drug candidates on the functionality of the skeletal muscle tissues, thus providing deeper insight into the real impact of these treatments. Overall, our findings underscore the potential of bioengineered 3D skeletal muscle technology to advance DMD research and facilitate the development of novel therapies for DMD and related neuromuscular disorders., (Creative Commons Attribution license.)

This study aims to understand airline passengers' satisfaction trends by analyzing the most influential factors on satisfaction before and during the COVID-19 pandemic. The sample consists of a dataset with 9745 passenger reviews published on airlinequality.com. The reviews were analyzed with a sentiment analysis tool calibrated for the aviation industry for accuracy. Machine learning algorithms were then implemented to predict review sentiment based on airline company, travelers' type and class, and country of origin. Findings show passengers were unhappy before the pandemic, aggravated after the COVID-19 outbreak. The staff's behavior is the main factor influencing passengers' satisfaction. Predictive modeling showed that it is possible to predict negative review sentiments with satisfactory performance rather than positive reviews. The main takeaway is that passengers, after the pandemic, are most worried about refunds and aircraft cabin cleanliness. From a managerial standpoint, airline companies can benefit from the created knowledge to adjust their strategies in agreement and meet their customers' expectations., (© 2023 The Authors.)

Lignocellulosic biomasses have a complex and compact structure, requiring physical and/or chemical pretreatments to produce glucose before hydrolysis. Mathematical modeling of enzymatic hydrolysis highlights the interactions between cellulases and cellulose, evaluating the factors contributing to reactor scale-up and conversion rates. Furthermore, this study evaluated the influence of two pretreatments (hydrothermal and organosolv) on the kinetics of enzymatic hydrolysis of sugarcane bagasse. The kinetic parameters of the model were estimated using the Pikaia genetic algorithm with data from the experimental profiles of cellulose, cellobiose, glucose, and xylose. The model considered the phenomenon of non-productive adsorption of cellulase on lignin and inhibition of cellulase by xylose. Moreover, it included the behavior of cellulase adsorption on the substrate throughout hydrolysis and kinetic equations for obtaining xylose from xylanase-catalyzed hydrolysis of xylan. The model for both pretreatments was experimentally validated with bagasse concentration at 10% w / v . The Plackett-Burman design identified 17 kinetic parameters as significant in the behavior of process variables. In this way, the modeling and parameter estimation methodology obtained a good fit from the experimental data and a more comprehensive model.

Background: Seed dispersal is a critical process in plant colonisation and demography. Fruits and seeds can be transported by several vectors (typically animals, wind and water), which may have exerted strong selective pressures on plant's morphological traits. The set of traits that favour dispersal by a specific vector have been historically considered as seed dispersal syndromes. As seed dispersal syndromes have a great potential to predict how seeds move (i.e. the relative importance of the standard mechanisms of seed dispersal), they have attracted the attention of naturalists and researchers for centuries. However, given that observations of actual dispersal events and colonisation are seldom reported, there is still much confusion in current studies failing to properly discriminate between seed dispersal syndromes (i.e. sets of traits that favour a particular mechanism) and actual seed dispersal (i.e. the vector that moves a given seed in one dispersal event). This distinction is important because the presence of any seed dispersal syndrome does not preclude the seed being occasionally dispersed by other non-standard mechanisms (i.e. different from the one predicted). Similarly, the absence of seed dispersal syndromes does not prevent seeds from being dispersed. The correct coding of seed dispersal syndromes thus requires a systematic and evolutive, rather than a phenomenological approach. Unfortunately, such approach has rarely been implemented at a community-level and no comprehensive datasets of seed dispersal syndromes are yet available for any entire flora., New Information: This database contains categorisation of the native European flora into eight seed dispersal syndromes. Information for a total of 9,874 species retrieved from the volumes of Flora Europaea were analysed. Earlier versions of this database, which only coded for the presence of four long-distance dispersal syndromes (endozoochorous, epizoochorous, thalassochorous and anemochorous diaspores), were used in four previous studies. Here, we present a fully revised and expanded database, including the presence of four additional short-distance dispersal syndromes (myrmecochorous, vertebrate hoarding, freshwater hydrochorous and ballochorous diaspores), a nomenclatural update for all species and the codification of 416 additional species.Roughly half (51.3%) of the native European flora produce diaspores without traits clearly associated with facilitating seed dispersal. The other half (48.7%) of the European plant species produces diaspores with some specialised traits associated with seed dispersal, most of which (79.9%) with a potential to facilitate long-distance dispersal events. The most common diaspores are those with anemochorous (23.5%), epizoochorous (8.0%), endozoochorous (7.8%), myrmecochorous (7.2%), thalassochorous (2.3%), freshwater dispersal (2.1%), ballochorous (4.6%) and vertebrate hoarding associated traits (0.2%). Two-thirds (66.3%) of the European shrub and tree species have diaspores with some specialisation for biotic seed dispersal., (Pablo Vargas, Ruben Heleno, José M. Costa.)

About 0.3% of all variants are due to de novo mobile element insertions (MEIs). The massive development of next-generation sequencing has made it possible to identify MEIs on a large scale. We analyzed exome sequencing (ES) data from 3232 individuals (2410 probands) with developmental and/or neurological abnormalities, with MELT, a tool designed to identify MEIs. The results were filtered by frequency, impacted region and gene function. Following phenotype comparison, two candidates were identified in two unrelated probands. The first mobile element (ME) was found in a patient referred for poikilodermia. A homozygous insertion was identified in the FERMT1 gene involved in Kindler syndrome. RNA study confirmed its pathological impact on splicing. The second ME was a de novo Alu insertion in the GRIN2B gene involved in intellectual disability, and detected in a patient with a developmental disorder. The frequency of de novo exonic MEIs in our study is concordant with previous studies on ES data. This project, which aimed to identify pathological MEIs in the coding sequence of genes, confirms that including detection of MEs in the ES pipeline can increase the diagnostic rate. This work provides additional evidence that ES could be used alone as a diagnostic exam., (© 2022. The Author(s), under exclusive licence to European Society of Human Genetics.)

Immunoassays show great potential for the detection of low levels of cytokines, due to their high sensitivity and excellent specificity. There is a particular demand for biosensors that enable both high-throughput screening and continuous monitoring of clinically relevant cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα). To this end, we here introduce a novel bioluminescent immunoassay based on the ratiometric plug-and-play immunodiagnostics (RAPPID) platform, with an improved intrinsic signal-to-background and an >80-fold increase in the luminescent signal. The new dRAPPID assay, comprising a dimeric protein G adapter connected via a semiflexible linker, was applied to detect the secretion of IL-6 by breast carcinoma cells upon TNFα stimulation and the production of low concentrations of IL-6 (∼18 pM) in an endotoxin-stimulated human 3D muscle tissue model. Moreover, we integrated the dRAPPID assay in a newly developed microfluidic device for the simultaneous and continuous monitoring of changes in IL-6 and TNFα in the low-nanomolar range. The luminescence-based read-out and the homogeneous nature of the dRAPPID platform allowed for detection with a simple measurement setup, consisting of a digital camera and a light-sealed box. This permits the usage of the continuous dRAPPID monitoring chip at the point of need, without the requirement for complex or expensive detection techniques.

Background and Objective: GLUT1 deficiency syndrome (Glut1DS) is a treatable neurometabolic disease that causes a wide range of neurologic symptoms in children and adults. However, its diagnosis relies on an invasive test, that is, a lumbar puncture (LP) to measure glycorrhachia, and sometimes complex molecular analyses of the SLC2A1 gene. This procedure limits the number of patients able to receive the standard of care. We wished to validate the diagnostic performance of METAglut1, a simple blood test that quantifies GLUT1 on the erythrocyte surface., Methods: We performed a multicenter validation study in France, involving 33 centers. We studied 2 patient cohorts: a prospective cohort consisting of patients with a clinical suspicion of Glut1DS explored through the reference strategy, that is, LP and analyses of the SLC2A1 gene, and a retrospective cohort that included patients previously diagnosed with Glut1DS. All patients were blind-tested with METAglut1., Results: We analyzed 428 patients in the prospective cohort, including 15 patients newly diagnosed with Glut1DS, and 67 patients in the retrospective cohort. METAglut1 was 80% sensitive and >99% specific for the diagnosis of Glut1DS. Concordance analyses showed a substantial agreement between METAglut1 and glycorrhachia. In the prospective cohort, the positive predictive value of METAglut1 was slightly higher than that of glycorrhachia. METAglut1 succeeded to identify patients with Glut1DS with SCL2A1 mosaicism and variants of unknown significance., Discussion: METAglut1 is an easily performed, robust, and noninvasive diagnostic test for the diagnosis of Glut1DS, which allows wide screening of children and adults, including those with atypical forms of this treatable condition., Classification of Evidence: This study provides Class I evidence that a positive METAglut1 test accurately distinguishes patients with suspected GLUT1 deficiency syndrome from other neurologic syndromes as compared with invasive and genetic testing., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Muscular dystrophies are a heterogeneous group of highly debilitating diseases that result in muscle atrophy and weakness. The lack of suitable cellular and animal models that reproduce specific aspects of their pathophysiology is one of the reasons why there are no curative treatments for these disorders. This highlights a considerable gap between current laboratory models and clinical practice. We strongly believe that organs-on-chip could help to fill this gap. Organs-on-chip, and in particular muscles-on-chip, are microfluidic devices that integrate functional skeletal muscle tissues. Biosensors in these systems allow monitoring of muscle homeostasis or drug responses in situ. This Perspective outlines the potential of organs-on-chip as advanced models for muscular dystrophies, as well as the current challenges and future opportunities for this technology., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

The wine sector faces important challenges related to sustainability issues and the impact of climate change. More frequent extreme climate conditions (high temperatures coupled with severe drought periods) have become a matter of concern for the wine sector of typically dry and warm regions, such as the Mediterranean European countries. Soil is a natural resource crucial to sustaining the equilibrium of ecosystems, economic growth and people's prosperity worldwide. In viticulture, soils have a great influence on crop performance (growth, yield and berry composition) and wine quality, as the soil is a central component of the terroir . Soil temperature (ST) affects multiple physical, chemical and biological processes occurring in the soil as well as in plants growing on it. Moreover, the impact of ST is stronger in row crops such as grapevine, since it favors soil exposition to radiation and favors evapotranspiration. The role of ST on crop performance remains poorly described, especially under more extreme climatic conditions. Therefore, a better understanding of the impact of ST in vineyards (vine plants, weeds, microbiota) can help to better manage and predict vineyards' performance, plant-soil relations and soil microbiome under more extreme climate conditions. In addition, soil and plant thermal data can be integrated into Decision Support Systems (DSS) to support vineyard management. In this paper, the role of ST in Mediterranean vineyards is reviewed namely in terms of its effect on vines' ecophysiological and agronomical performance and its relation with soil properties and soil management strategies. The potential use of imaging approaches, e.g. thermography, is discussed as an alternative or complementary tool to assess ST and vertical canopy temperature profiles/gradients in vineyards. Soil management strategies to mitigate the negative impact of climate change, optimize ST variation and crop thermal microclimate (leaf and berry) are proposed and discussed, with emphasis on Mediterranean systems., 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 © 2023 Costa, Egipto, Aguiar, Marques, Nogales and Madeira.)

The rechargeable alkaline aqueous zinc-air batteries (ZABs) are prospective candidates to supply the energy demand for their high theoretical energy density, inherent safety, and environmental friendliness. However, their practical application is mainly restricted by the unsatisfactory efficiency of the air electrode, leading to an intense search for high-efficient oxygen electrocatalysts. In recent years, the composites of carbon materials and transition metal chalcogenides (TMC/C) have emerged as promising alternatives because of the unique properties of these single compounds and the synergistic effect between them. In this sense, this review presented the electrochemical properties of these composites and their effects on the ZAB performance. The operational fundamentals of the ZABs were described. After elucidating the role of the carbon matrix in the hybrid material, the latest developments in the ZAB performance of the monometallic structure and spinel of TMC/C were detailed. In addition, we report topics on doping and heterostructure due to the large number of studies involving these specific defects. Finally, a critical conclusion and a brief overview sought to contribute to the advancement of TMC/C in the ZABs., 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 Elsevier B.V. All rights reserved.)

Objective: Although there is growing evidence associating nonfunctioning adrenal incidentalomas (NFAI) with cardiovascular risk factors, there are limited data whether NFAI and autonomous cortisol secretion (ACS) groups have similar or different clinical and metabolic features. The aim of this study is to compare cardiometabolic clinic parameters among patients with ACS and NFAI, as well as controls., Design: Cross-sectional study., Patients: Eighty nine NFAI, 58 ACS and 64 controls were evaluated., Measurements: Diagnosis of NFAI (1 mg dexamethasone suppression test [1 mg-DST] ≤50 nmol/L [≤1.8 μg/dl]) and ACS (1 mg-DST > 50 nmol/L [> 1.8 μg/dl]) was established according to current guidelines. The control group was selected based on a normal adrenal imaging exam., Results: There were no differences between groups regarding age, gender, ethnicity, menopause or body mass index. Patients with adrenal incidentaloma presented higher frequency of hypertension (74.1 vs. 57.8%; p = .02), resistant hypertension (45.4 vs. 9.4%; p < .001), dyslipidemia (80.1 vs. 63.9%; p = .01), as well as metabolic syndrome (84.2 vs. 61.7%; p = .001) compared to the controls, respectively. NFAI and ACS patients presented similar frequency of arterial hypertension (70.8 vs. 79.3%) and resistant hypertension (41.3 vs. 51.1%), dyslipidemia (79.3 vs. 81.5%) and metabolic syndrome (83.3 vs. 85.7%); also, levels of HbA1c were similar between the groups. Binary logistic regression showed that NFAI (p = .004) and ACS (p = .001) were independent predictors for resistant hypertension (p = .003); also, ACS was an independent predictor for metabolic syndrome (p = .04)., Conclusions: NFAI and ACS presented a higher frequency of cardiometabolic morbidities in comparison with individuals with normal adrenal glands. Additionally, we demonstrated that both ACS and NFAI groups have similar cardiometabolic conditions., (© 2022 John Wiley & Sons Ltd.)

This systematic review aimed to investigate the occurrence of phthalates (phthalic acid esters [PAEs]) in different food matrices, as well as report the main sources of PAEs in food, the potential risks to the population, and the factors that influence its migration from food contact materials (FCMs) to food. Nineteen PAEs were identified, including di-(2-ehtylhexyl) phthalate (DEHP), dibutyl-phthalate (DBP), benzylbutyl phthalate (BBP), diisononyl phthalate (DINP), and diisodecyl phthalate (DIDP) in fruits and vegetables, milk and dairy products, cereals, meat, fish, fat and oils, snacks, condiments and sauces, miscellaneous, and baby food. Fifty-seven values of PAEs were above the legal limits of countries. DEHP is the PAE with the highest incidence, with maximum concentrations above the specific migration limit (SML) for milk and dairy products, oils and fats, fish, cereals, condiments and sauces, meat, and fruits and vegetables. The risk of exceeding the tolerable daily intake (TDI) was high for DEHP and DBP in fish, fat and oils, cereals, and milk and dairy products for children and adults. Fat and oils are the most critical food for DEHP, DBP, BBP, and DINP. Comparing the estimated daily intake (EDI) with the TDI, there was a risk for "milk and dairy products" in adults and for "cereal and cereal products" in children concerning DEHP. "Cereal and cereal products" presented a risk in children and adults concerning DBP. The "fat and oils" category presented a risk in children and adults about DBP and DINP. Temperature, contact time between food and the FCM, fat percent, and acidity positively correlate with the PAE's migration. The contamination occurs in many steps of the production chain., (© 2023 Institute of Food Technologists®.)