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Background: LAMVYX was a multicenter, single‐arm, phase 2 trial designed to validate the safety and efficacy of CPX‐351 in patients aged 60–75 years with newly diagnosed, secondary acute myeloid leukemia and to generate evidence on key issues not addressed in the preceding regulatory pivotal trial. Methods: The primary end point of the study was the complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate after induction. Eligible patients were recommended to undergo allogeneic hematopoietic stem cell transplantation after the first consolidation cycle. Alternatively, patients could undergo up to six maintenance cycles with CPX‐351. Results: Twenty‐nine patients (49%; 95% exact confidence interval [CI], 37%–62%) patients achieved a CR/CRi after one or two cycles of induction, with a measurable residual disease negativity rate of 67% as assessed by centralized, multiparameter flow cytometry. Among patients who had serial next‐generation sequencing analyses available, clearance of somatic mutations that were present at diagnosis was achieved in 7 (35%). The median follow‐up among survivors was 16.8 months (range, 8.7–24.3 months). The median event‐free survival was 3.0 months (95% CI, 1.4–7.3 months), and the median overall survival was 7.4 months (95% CI, 3.7–12.7 months). In landmark analyses at day +100 from diagnosis, the 1‐year overall and event‐free survival rate among patients who underwent allogeneic hematopoietic stem cell transplantation was 70% (95% CI, 47%–100%) and 70% (95% CI, 47%–100%), respectively. The corresponding values were 89% (95% CI, 71%–100%) and 44% (95% CI, 21%–92%), respectively, for patients who entered the maintenance phase. No significant longitudinal changes were observed in severity index or quality‐of‐life visual analog scale scores. Conclusions: The current data provide novel insights that might inform the clinical positioning and optimal use of CPX‐351, complementing previous results (ClinicalTrials.gov identifier NCT04230239). In a phase 2 trial among older patients with secondary acute myeloid leukemia, treatment with CPX‐351 resulted in a complete remission/complete remission with incomplete hematologic recovery rate similar to that reported in the pivotal trial, with long‐term clinical benefit largely restricted to patients who underwent allogeneic hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Problem: Intrauterine infection is one of the most jeopardizing conditions associated with adverse outcomes, including preterm birth; however, multiple tolerance mechanisms operate at the maternal–fetal interface to avoid the rejection of the fetus. Among the factors that maintain the uterus as an immunoprivileged site, Galectin‐1 (Gal‐1), an immunomodulatory glycan‐binding protein secreted by the maternal‐fetal unit, is pivotal in promoting immune cell homeostasis. This work aimed to evaluate the role of Gal‐1 during a lipopolysaccharide (LPS)‐induced‐inflammatory milieu. Method of Study: Using an ex vivo culture with two independent compartments, human fetal membranes at term were pretreated with 40 and 80 ng/mL of Gal‐1, then to reproduce an intraamniotic inflammation, the fetal side of membranes was stimulated with 500 ng/mL of LPS for 24 h. The concentrations of tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, monocyte chemoattractant protein (MCP1), macrophage inflammatory protein (MIP1) α, regulated upon activation normal T cell expressed and secreted (RANTES), and matrix metalloproteinase (MMP)‐9 were measured in both amnion and choriodecidua compartments. Results: In a tissue‐specific fashion profile, pretreatment with the physiologic concentration of Gal‐1 significantly diminished the LPS‐dependent secretion of TNF‐α, IL‐1β, Il‐6, MCP1, MIP1α, RANTES, and MMP‐9. Conclusion: Gal‐1 elicits an anti‐inflammatory effect on the human fetal membranes stimulated with LPS, which supports the hypothesis that Gal‐1 is part of the immunomodulatory mechanisms intended to stop the harmful effect of inflammation of the maternal–fetal interface. [ABSTRACT FROM AUTHOR]

Summary: Early stress detection of crops requires a thorough understanding of the signals showing the very first symptoms of the alterations in the photosynthetic light reactions. Detection of the activation of the regulated heat dissipation mechanism is crucial to complement passively induced fluorescence to resolve ambuiguities in energy partitioning.Using leaf spectroscopy, we evaluated the capability of pigment spectral unmixing to calculate the fluorescence quantum efficiency (FQE) and simultaneously retrieve fast absorption changes in a drought and nitrogen deficiency experiment with tomato. In addition, active fluorescence measurements and pigment analyses of xanthophylls, carotenes and chlorophylls were conducted.We observed notable responses in noninvasive proximal sensing‐retrieved FQE values under stress, but as expected, these alone were not enough to identify the constraints in photosynthetic efficiency. Reflectance‐based detection of the 535‐nm peak absorption change was able to complement FQE and indicate the activation of regulated heat dissipation for both stress treatments under growing light conditions. However, further complexity in the light harvesting energy regulation needs to be accounted for when considering additional light stress.Our results underscore the potential of complementary in vivo quantitative spectroscopy‐based products in the early and nondestructive stress diagnosis of plants, marking the path for further applications. [ABSTRACT FROM AUTHOR]

Summary: Grasses (Poaceae) comprise c. 11 800 species and are central to human livelihoods and terrestrial ecosystems. Knowing their relationships and evolutionary history is key to comparative research and crop breeding. Advances in genome‐scale sequencing allow for increased breadth and depth of phylogenomic analyses, making it possible to infer a new reference species tree of the family.We inferred a comprehensive species tree of grasses by combining new and published sequences for 331 nuclear genes from genome, transcriptome, target enrichment and shotgun data. Our 1153‐tip tree covers 79% of grass genera (including 21 genera sequenced for the first time) and all but two small tribes. We compared it to a newly inferred 910‐tip plastome tree.We recovered most of the tribes and subfamilies previously established, despite pervasive incongruence among nuclear gene trees. The early diversification of the PACMAD clade could represent a hard polytomy. Gene tree–species tree reconciliation suggests that reticulation events occurred repeatedly. Nuclear–plastome incongruence is rare, with very few cases of supported conflict.We provide a robust framework for the grass tree of life to support research on grass evolution, including modes of reticulation, and genetic diversity for sustainable agriculture. [ABSTRACT FROM AUTHOR]

Background: Patients with secondary acute myeloid leukemia who previously received hypomethylating agents for prior myeloid neoplasms (HMA‐sAML) face a dismal prognosis. Methods: The authors analyze the characteristics, therapeutic approaches, and outcomes of patients with HMA‐sAML from the Programa Español para el Tratamiento de Hemopatías Malignas (PETHEMA) registry. Results: A total of 479 patients were included, mostly from prior myelodysplastic syndrome (84%). Frontline therapy consisted of intensive chemotherapy (IC) in 31%, low‐dose cytarabine‐based in 19%, supportive care and clinical trial 17% each, and HMA‐based therapy in 12% and 4% in venetoclax‐based regimen. Complete remission was achieved in 95 patients (27%), with higher rate among IC and venetoclax‐based groups (44% and 41%, respectively). The median overall survival (OS) was 4.93 months, with 7.68 months for IC patients, 7.82 months after HMA monotherapy, and 4.66 months after venetoclax‐based regimens. Patients who underwent allogeneic hematopoietic stem cell transplantation in first remission (n = 33, 9%) had a better survival outcome (median OS not reached). Multivariate analyses identified age (≥65 years), Eastern Cooperative Oncology Group >2, higher white blood cell count, and adverse risk cytogenetic as adverse prognostic factors, whereas NPM1 mutation was a favorable factor. Conclusions: Patients with HMA‐sAML have a poor prognosis and suboptimal outcomes with conventional treatments, including BCL2 inhibitors, highlighting the need for clinical trials targeting this population. This study analyzes the characteristics and outcomes of adults with secondary acute myeloid leukemia who previously received hypomethylating agents for prior myeloid neoplasms (HMA‐sAML). This analysis of 479 patients from the PETHEMA registry shows a poor overall survival of 4.93 months with suboptimal outcomes, highlighting the unmet clinical need for this population. Whenever is feasible, fit HMA‐sAML patients should undergo an allo‐hematopoietic stem cell transplantation in first remission. [ABSTRACT FROM AUTHOR]

Aim: Maternal health and gestational control are crucial to improving the newborn's prognosis. This study analyses demographic and obstetric factors at the beginning of pregnancy related to neonatal health, assessing their impact on the risk of hospital admission and prematurity. Methods: Observational retrospective study conducted in Northeast Spain with data of 9560 newborns between February 2017 and February 2022. The following have been evaluated as risk factors for hospital admission: nulliparity, multiple gestation, fertilisation techniques, foreign maternal origin, maternal age, smoking and residential location, dividing the sample according to gestational age. Hypothesis testing and logistic regression were performed. Results: Nulliparity, fertilisation techniques and multiple gestation represent a risk factor for neonatal admission (OR 22.48, 4.04 and 3.34, respectively), especially in premature newborns <32 weeks of GA (OR: 30.71, 10.71 and 22.76, respectively). Foreign maternal origin also adds risk of admission, both in term newborns (OR 1.26; CI: 1.10–1.43) and in premature babies <32 weeks of GA (OR 1.61; CI: 1.09–2.38). Tobacco does not present a significant risk of neonatal admission. The multivariate analysis model confirms the influence of the following factors in all the studied groups: nulliparity, multiple gestation and foreign maternal origin. Conclusions: Nulliparity and multiple pregnancies are both main risk factors for neonatal admission and premature delivery. The use of fertilisation techniques and the foreign origin of the mother significantly associate increased risk of admission and neonatal prematurity. These findings underscore the need for a comprehensive approach to prenatal care to improve neonatal prognosis and promote long‐term health in risk populations. [ABSTRACT FROM AUTHOR]

Background: Herein, we present the results of the phase 2 IMMUNOSARC study (NCT03277924), investigating sunitinib and nivolumab in adult patients with advanced bone sarcomas (BS). Methods: Progressing patients with a diagnosis of BS were eligible. Treatment was comprised of sunitinib (37.5 mg/day on days 1–14, 25 mg/day afterword) plus nivolumab (3 mg/kg every 2 weeks). Primary end point was progression‐free survival rate (PFSR) at 6 months based on central radiology review. Secondary end points were overall survival (OS), overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and safety. Results: A total of 46 patients were screened, 40 patients entered the study, and 38 underwent central radiological review and were evaluable for primary end point. Median age was 47 years (range, 21–74). Histologies include 17 (43%) osteosarcoma, 14 chondrosarcoma (35%, 10 conventional, four dedifferentiated [DDCS]), eight (20%) Ewing sarcoma, and one (2%) undifferentiated pleomorphic sarcoma. The PFSR at 6 months was 42% (95% confidence interval [CI], 27–58). With a median follow‐up of 39.8 months (95% CI, 37.9–41.7), the median PFS and OS were 3.8 months (95% CI, 2.7–4.8) and 11.9 months (95% CI, 5.6–18.2). ORR by RECIST was 5%, with two of 38 partial responses (one of four DDCS and one of 17 osteosarcoma), 19 of 38 (50%) stable disease, and 17 of 38 (45%) progressions. Grade ≥3 adverse events were neutropenia (six of 40, 15%), anemia (5/40, hypertension (6/40, 15%), 12.5%), ALT/AST elevation (5/40, 12.5%), and pneumonitis (1/40, 2.5%). Seventeen percent of patients discontinued treatment due to toxicity, including a treatment‐related grade 5 pneumonitis Conclusion: The trial met its primary end point in the BS cohort with >15% of patients progression‐free at 6 months. However, the toxicity profile of this regimen was relevant. With a progression‐free survival of 42% at 6 months, this trial with nivolumab and sunitinib in 40 patients with advanced bone sarcoma met its primary end point. The response rate was high (25%) in patients with dedifferentiated chondrosarcoma (DDCS) and an international expansion phase 2 trial in DDCS is currently enrolling. [ABSTRACT FROM AUTHOR]

The development of narrow bandgap A‐D‐A‐ and ADA′DA‐type non‐fullerene small molecule acceptors (NFSMAs) along with small molecule donors (SMDs) have led to significant progress in all‐small molecule organic solar cells. Remarkable power conversion efficiencies, nearing the range of 17–18 %, have been realized. These efficiency values are on par with those achieved in OSCs based on polymeric donors. The commercial application of organic photovoltaic technology requires the design of more efficient organic conjugated small molecule donors and acceptors. In recent years the precise tuning of optoelectronic properties in small molecule donors and acceptors has attracted considerable attention and has contributed greatly to the advancement of all‐SM‐OSCs. Several reviews have been published in this field, but the focus of this review concerns the advances in research on OSCs using SMDs and NFSMAs from 2018 to the present. The review covers the progress made in binary and ternary OSCs, the effects of solid additives on the performance of all‐SM‐OSCs, and the recently developed layer‐by‐layer deposition method for these OSCs. Finally, we present our perspectives and a concise outlook on further advances in all‐SM‐OSCs for their commercial application. [ABSTRACT FROM AUTHOR]

Background and Objective: Patients with pulmonary hypertension (PH) may present with hypoxaemia at rest or during daily activities. There is no epidemiological data on the prescription of long‐term oxygen therapy (LTOT) in patients with PH. The study sought to analyse the prevalence and incidence of LTOT prescription among patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) in Spain and to determine predictors for this prescription. Methods: A retrospective analysis was performed from the Spanish Registry of Pulmonary Arterial Hypertension (REHAP). Collected data included demographics and anthropometric measurements, functional class (FC), arterial blood gases, pulmonary function tests, haemodynamic measurements, six‐minute walking distance (6MWD) and LTOT prescription. In addition, we assessed the prevalence and incidence of LTOT prescription by PH group and subtype and potential predictors for LTOT initiation in the first 5 years after diagnosis. Results: We analysed 4533 patients (69.9% PAH and 30.1% CTEPH), mostly female (64.5%), with a mean age of 53.0 ± 18.3 years. The prevalence of LTOT was 19.3% for all patients. The incidence of LTOT prescriptions decreased from 5.6% to 1.6% between 2010 and 2019, respectively. Predictors for LTOT prescription, excluding those that represent the indication for oxygen therapy were: FC (HR: 1.813), 6MWD (HR: 1.002), mean pulmonary arterial pressure (mPAP) (HR: 1.014), cardiac index (CI) (HR: 1.253), pulmonary vascular resistance (PVR) (HR: 1.023) and diffusing capacity of carbon monoxide (DLCO) (HR: 1.294). Conclusion: The prevalence of LTOT in PAH and CTEPH patients is close to 20%. FC, 6MWD, mPAP, CI, PVR and DLCO were predictors for LTOT prescription. [ABSTRACT FROM AUTHOR]

Fishes inhabiting the mesopelagic zone of the world's oceans are estimated to account for the majority of the world's fish biomass. They have recently attracted new attention because they are part of the biological carbon pump and have been reconsidered as a contribution to food security. Hence, there is an urgent need to understand how environmental conditions and species interactions shape their assemblages, and how they contribute to the functioning of marine ecosystems. Trait‐based approaches are valuable for addressing these types of questions. However, the biology and ecology of mesopelagic fishes are understudied compared to fishes in shallow and epipelagic waters. Here, we synthesise existing knowledge of traits of mesopelagic fishes and relate them to their role in survival, feeding and growth and reproduction, the key functions that contribute to fitness. Vertical migrations, specialised vision and the use of bioluminescence are among the most striking adaptations to the conditions in the mesopelagic realm. Many traits are interrelated as a result of trade‐offs, which may help to understand selection pressures. While morphological traits are straightforward to observe, major knowledge gaps exist for traits that require frequent sampling, assessment under experimental conditions or age determination. The unique adaptations of mesopelagic fishes need to be included in management strategies as well as fundamental research of the habitat. [ABSTRACT FROM AUTHOR]

Background: Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease with poor prognosis. It is known that the activation of STAT3 signaling pathways promotes the development and progression of this neoplasia and it has been described the role of PTPRT as a negative regulator of STAT3. Then, we have evaluated the impact of them as biomarkers of outcome in a series of patients with recurrent and/or metastatic SCCHN treated with weekly paclitaxel‐plus‐cetuximab (ERBITAX) regimen. Patients and methods: Between 2008 and 2017, 52 patients with recurrent/metastatic SCCHN were treated with ERBITAX at our center, 34 of whom had available tumor samples. Phosphorylated STAT3 (pSTAT3) protein expression was analyzed by immunohistochemistry, STAT3 mRNA expression by qPCR, and PTPRT promoter methylation by methylation‐specific PCR. Molecular results were correlated with response rate (RR), progression‐free survival (PFS), and overall survival (OS). Results: pSTAT3 overexpression was detected in 67% and PTPRT promoter hypermethylation in 41% of tumor samples. PTPRT promoter hypermethylation showed a trend towards an association with lower RR (21% vs. 60%; p = 0.06). A lower RR was also observed in patients with pSTAT3 overexpression (36% vs. 54%) and in those with high STAT3 mRNA levels (43% vs. 64%), but these differences did not reach statistical significance. PTPRT promoter hypermethylation correlated with pSTAT3 overexpression (p = 0.009) but not with STAT3 mRNA overexpression. OS and PFS was shorter in patients with activated STAT3, but the difference did not reach statistical significance. Conclusions: Although this was a relatively small retrospective study, it provides preliminary indications of the potential role of the STAT3 pathway on outcome in SCCHN and confirms that PTPRT acts as a negative regulator of STAT3. Our findings warrant investigation in a larger patient cohort to determine if inactivating this pathway through specific targeted treatments could improve outcomes in recurrent/metastatic SCCHN patients. [ABSTRACT FROM AUTHOR]

There is disagreement amongst political theorists as to whether a European demos based on a culturally grounded identity as a precondition for a stronger integration of the European Union (EU) exists. We study a part of this question from a constructivist perspective by analysing how individuals in Europe perceive European culture and how this perception is related to support for the EU. We focus on the following questions: (a) whether European respondents perceive a shared European culture, (b) whether they consider this culture to be of higher value than other cultures and (c) whether they are proud of European cultures. We study these questions on the basis of a survey conducted in 2021 in nine European countries, including both EU and non‐EU countries. Our results show that the perception of a shared European culture and its positive evaluation, both inclusive and exclusive, covary positively with support for the EU. [ABSTRACT FROM AUTHOR]

ABSTRACT An in‐depth analysis of susceptibility factors modifying the penetrance of rare Leber hereditary optic neuropathy‐causing mutations in respiratory complex I genes encoded in mitochondrial deoxyribonucleic acid has not been performed. To bridge this gap, we conducted a review of the literature on rare mutations associated with LHON, selected those with substantial evidence of pathogenicity, and performed an in‐depth analysis of the various pedigrees. Examining the influences that modify the penetrance of the classical mutations associated with this disease may offer insights into susceptibility factors in individuals carrying the rare mutations. [ABSTRACT FROM AUTHOR]

A simple and efficient method was developed to prepare the novel fluorescent tetra‐substituted thiophene derivatives. This method involves using the Gewald's conditions, followed by the Vilsmeier–Haack–Arnold (VHA) formylation. By judiciously controlling the use of the VHA reagent, we have selectively introduced a formyl group into position 5 of the thiophene. This had a direct impact on its fluorescence properties. The resulting compounds have showed an intense fluorescence in the emission wavelength range of 420–500 nm with a 10−6 M concentration. All new products have been structurally confirmed by spectroscopic data. The structure of compound 2g was confirmed by single‐crystal X‐ray diffraction. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion The identification of a heterozygous exonic GGC repeat expansion in ZFHX3 underlying spinocerebellar ataxia type 4 (SCA4) has solved a 25‐year diagnostic conundrum. We used adaptive long‐read sequencing to decipher the pathogenic expansion in the index Utah family and an unrelated family from Iowa of Swedish ancestry. Contemporaneous to our discovery, other groups identified the same repeat expansion in affected individuals from Utah, Sweden, and Germany, highlighting the current pivotal time for detection of novel repeat expansion disorders.Given that the pathogenic repeat expansion is rare on a population level, we proposed a common ancestor across all families. Here, we employed targeted long‐read sequencing through adaptive sampling, enriching for the chr16q22 region of interest.Using phased sequencing results from individuals from Utah, Iowa, and Southern Sweden, we confirmed a common ~2000‐year‐old ancestral haplotype harbouring the repeat expansion.This study provides further insight into the genetic architecture of SCA4. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

The lack of selectivity toward the oxygen reduction reaction (ORR) in metal nanoparticles can be linked to the generation of intermediates. This constitutes a crucial constraint on the performance of specific electrochemical devices, such as fuel cells and metal–air batteries. To boost selectivity of metal nanoparticles, a novel methodology that harnesses the unique electrocatalytic properties of polyoxometalates (POM) to scavenge undesired intermediates of the ORR (such as HO2−) promoting selectivity is proposed. It involves the covalent functionalization of metal nanoparticle's surface with an electrochemically active capping layer containing a new sulfur‐functionalized vanadium‐based POM (AuNP@POM). To demonstrate this approach, preformed thiolate Au(111) nanoparticles with a relatively poor ORR selectivity are chosen. The dispersion of AuNP@POM on the surface of carbon nanofibers (CNF) enhances oxygen diffusion, and therefore the ORR activity. The resulting electrocatalyst (AuNP@POM/CNF) exhibits superior stability against impurities like methanol and a higher pH tolerance range compared to the standard commercial Pt/C. The work demonstrates for the first time, the use of a POM‐based electrochemically active capping layer to switch on the selectivity of poorly selective gold nanoparticles, offering a promising avenue for the preparation of electrocatalyst materials with improved selectivity, performance, and stability for ORR‐based devices. [ABSTRACT FROM AUTHOR]

The article discusses the impact of global change on water-driven ecological and biogeochemical corridors in the Polar-Alpine biome. It highlights how longer thaw phases and more frequent dry periods are transforming transitional ecosystems, potentially leading to biotic homogenization and a loss of biodiversity. The study emphasizes the importance of understanding water-driven connectivity dynamics and the potential consequences of fluctuating connectivity on biodiversity distribution. The authors call for further research to safeguard species, metacommunity dynamics, and ecosystem functioning in the face of increasing biotic homogenization due to global change. [Extracted from the article]

The cognitive‐behavioral model of generalized Problematic Internet Use (PIU) is the theoretical approach that has obtained the most evidence on the study of this problem, which includes four components: Online Social Preference, Mood Regulation, Deficient Self‐Regulation, and Negative Outcomes. This study aimed to identify PIU profiles using Latent Profile Analysis, and to analyze the differences in them attending to some of the principal PIU risk and protective factors. A total of 675 Spanish adolescents completed questionnaires assessing PIU, Internet usage, mental health problems, personality, psychological strengths, and family relationships. Four profiles were obtained: Nonproblematic use (68.30% of the sample), Slightly problematic use (17.90% of the sample), Problematic use (8.50% of the sample), and Severe problematic use (5.40% of the sample). Results showed differences between them, with the profile with more PIU having more risk factors and less protective factors. Results showed that many different personal and social variables included in the study play a role in PIU. Knowing the different PIU profiles can help in the design of more specific and precise procedures and instruments for risk assessment, as well as aiding in prevention and in the design of more individualized treatments. [ABSTRACT FROM AUTHOR]

Background and purpose: The purpose was to describe the risk of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, hospitalization for coronavirus disease 2019 (COVID‐19) and related death and to assess the impact of the pandemic in the survival of amyotrophic lateral sclerosis (ALS) patients. Methods: The risk of SARS‐CoV‐2 infection, hospitalization for COVID‐19 and related death was assessed in ALS patients alive between March 2020 and July 2022. To evaluate its impact in the overall survival of ALS patients, the survival of patients who died before and during the pandemic was compared. Results: Amongst 263 ALS patients alive during the pandemic, 62 got infected during the study period (infection rate 14.34 per 100 person‐years). Most infections (68%) occurred during the sixth wave (November 2021 to January 2022) and most patients (67%) were vaccinated at the time of infection. The hospitalization rate due to COVID‐19 was 4.16 per 100 person‐years. The multivariable model confirmed non‐invasive ventilation (NIV) use prior to infection as a risk factor for hospitalization (odds ratio [OR] = 7.96, p = 0.003) and COVID‐19 vaccination as a protective factor (OR = 0.093, p = 0.025) independent of age, sex and gastrostomy. Within 30 days after infection, 7% of non‐ventilated patients started NIV and five patients (8.06%) died, of whom four were previously ventilated. The median survival of ALS patients was similar before and during the pandemic and no effect was found in the Cox regression model (hazard ratio 1.02, p = 0.89). Conclusions: This study shows a high risk of severe COVID‐19 amongst ALS patients requiring NIV. Nevertheless, the pandemic showed no impact in the overall survival of ALS patients, probably due to a high vaccination rate and an adequate access to healthcare resources. [ABSTRACT FROM AUTHOR]

This paper provides new empirical evidence on the role of landfill taxes in reducing landfill waste and promoting recycling. We focus on the impacts of the 2017 landfill tax law reform in Catalonia, a Spanish region, which increased the tax rate from 18 to 47 euros per tonne over the period 2017–20. Using municipality‐level data for Catalonia from the 2013–20 period, we contrast municipalities that differed in the use of door‐to‐door waste collection by the beginning of our study period. As door‐to‐door waste collection is advocated as especially efficient at reducing landfill waste, we hypothesise that municipalities that had not yet adopted this system had greater leeway in responding to the tax changes. Based on a two‐way fixed effects design, our findings reveal large differential responses to the tax hike. Compared with municipalities that had implemented door‐to‐door waste collection by 2013, we estimate that those that had not done this responded to the tax hike by reducing landfill waste by an additional 12 per cent, reducing total waste by 4 per cent, and increasing the share of recycled waste and waste that is sorted as organic by 6 and 2.5 percentage points, respectively. We provide suggestive evidence that the adoption of door‐to‐door waste collection is the main mechanism driving these responses. [ABSTRACT FROM AUTHOR]

Malaria remains a significant global health problem, mainly due to Plasmodium falciparum, which is responsible for most fatal infections. Infected red blood cells (iRBCs) evade spleen clearance by adhering to endothelial cells (ECs), triggering capillary blockage, inflammation, endothelial dysfunction and altered vascular permeability, prompting an endothelial transcriptional response. The iRBCIT4var04/HBEC‐5i model, where iRBCs present IT4var04 (VAR2CSA) on their surface, was used to analyze the effects of iRBC binding on ECs at different temperature (37°C vs. 40°C). Binding of non‐infected RBCs (niRBCs) and fever alone altered the expression of hundreds of genes in ECs. Comparing the expression profile of HBEC‐5i cells cultured either in the presence of iRBCs or in the presence of niRBCs revealed significant upregulation of genes linked to immune response, nucleosome assembly, NF‐kappa B signaling, angiogenesis, and antiviral immune response/interferon‐alpha/beta signaling. Raising the temperature to 40°C, simulating fever, led to further upregulation of many genes, particularly those involved in cytokine production and angiogenesis. In summary, the presence of iRBCs stimulates ECs, activating several immunological pathways and affecting antiviral (−parasitic) mechanisms and angiogenesis. Our data uncovered the induction of the interferon‐alpha/beta signaling pathway in ECs in response to iRBCs. [ABSTRACT FROM AUTHOR]

Background and Purpose: ITPR3 encodes type 3 inositol‐tri‐phosphate receptor (IP3R3), a protein expressed in Schwann cells, predominantly in the paranodal region, and involved in the regulation of Ca2+ release from the endoplasmic reticulum. Dominant variants in ITPR3 have recently been recognized as a rare cause of intermediate Charcot–Marie–Tooth disease (CMT). Methods: We collected the clinical data of a family with autosomal dominant neuropathy whose proband was diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) for many years. The genetic diagnosis was achieved by whole exome sequencing. Results: The proband developed symmetrical sensory–motor neuropathy with demyelinating features at 32 years old. He was diagnosed with CIDP and received numerous immunomodulatory treatments. However, his condition progressed, leading to severe proximal leg and hand atrophy that confined him to a wheelchair at 60 years. The patient's two sons began to exhibit symptoms suggestive of neuropathy shortly after age 30 years, and the condition was reoriented as inherited. Exome sequencing identified a heterozygous c.4271C > T variant in the ITPR3 gene segregating with the disease. Nerve conduction studies showed a combination of demyelinating and axonal features that vary by nerve, disease duration, and patient. A uniform thickening of the nerves was identified on nerve echography, as was distal symmetric fatty infiltration in lower limb muscle imaging. Conclusions: The c.4271C > T ITPR3 variant causes a late onset CMT that can be considered an intermediate CMT. Considering the electrophysiological findings and the distribution of IP3R3, we hypothesize that this variant could start as nodal dysfunction that progresses to widespread nerve degeneration. [ABSTRACT FROM AUTHOR]

This study investigates whether audiovisual phonetic training with hand gestures encoding visible or nonvisible articulation features has a differential impact on learning second language sounds. Ninety‐nine Catalan–Spanish bilingual students were trained to differentiate English /æ/ and /ʌ/, which differ in the visible lip aperture and nonvisible tongue position, with training involving no gestures, gestures representing the lip aperture, or gestures representing the tongue position. Before, immediately after, and 1 week after the training, participants' perception of the targets was assessed through a word‐identification task, and their production was tested through paragraph‐reading, picture‐naming, and word‐imitation tasks. Although all participants improved in perception and production, the lip hand gesture was more effective in adjusting lip aperture than the other two conditions in the paragraph‐reading and picture‐naming tasks. These results suggest that hand gestures encoding visible rather than nonvisible articulation features are more effective for improving second language pronunciation. A one‐page Accessible Summary of this article in nontechnical language is freely available in the Supporting Information online and at https://oasis‐database.org. [ABSTRACT FROM AUTHOR]

This conceptual article focuses on how a National Professional Development grant through the Office of English Language Acquisition in the U.S. Department of Education supported multilingual paraprofessionals' equitable access to and participation in high‐quality, ongoing professional development aimed at supporting young multilingual learners, and how they leveraged both prior and newfound knowledge and experiences during their participation. We understood that paraprofessionals had been positioned as less white, less English‐speaking, and less knowledgeable than their teacher counterparts and knew that their engagement needed to be utilized as a resource. Thus, we broadly draw on the concept of equity but specifically on the notions of funds of knowledge, translanguaging, and raciolinguistics as we document our process of working with Pre‐K–second grade paraprofessionals. [ABSTRACT FROM AUTHOR]

Identifying drivers that shape biodiversity across biogeographical regions is important to predict ecosystem responses to environmental changes. While β‐diversity has been widely used to describe biodiversity patterns across space, the dynamic assembly of species over time has been comparatively overlooked. Insights from terrestrial and marine studies on temporal β‐diversity has mostly considered environmental drivers, while the role of biotic mechanisms has been largely ignored. Here, we investigated patterns of temporal variation in β‐diversity of seagrass‐associated amphipods. We conducted a study in three biogeographical regions across a temperate to subtropical latitudinal gradient (approximately 2000 km, 13° of latitude in total). In each region, we randomly selected three Cymodocea nodosa meadows, totaling nine meadows sampled seasonally (i.e., four times per year) from 2016 to 2018. We partitioned temporal β‐diversity into its turnover (i.e., species replacement) and nestedness (i.e., differences in species composition caused by species losses) components and addressed the relative influence of both temporal variation in habitat structure (i.e., biotic driver) and environmental conditions on the observed β‐diversity patterns. Our study revealed high temporal β‐diversity of amphipod assemblages across the three biogeographical regions, denoting significant fluctuations in species composition over time. We identified species turnover as the primary driver of temporal β‐diversity, strongly linked to temporal variability in local habitat structure rather than to regional climatic drivers. Subtropical Atlantic meadows with high structural stability over time exhibited the largest turnover rates compared with temperate Mediterranean meadows, under lower structural stability, where nestedness was a more relevant component of temporal β‐diversity. Our results highlight the crucial role of habitat stability in modulating temporal β‐diversity patterns on animals associated with seagrasses, stressing the importance of monitoring variations in habitat structure over time for developing management plans and restoration actions in the context of diversity loss and fragmentation of ecosystems. [ABSTRACT FROM AUTHOR]

Coral reef ecosystems support high fish biodiversity through ecological interactions with structural complexity across multiple spatial scales including coral colony architecture and the surrounding seascape structure. In an era where the complexity of coral reef ecosystems is being diminished, understanding the importance of structural characteristics beyond single focal patches has the potential to better inform actions for protecting, restoring or creating habitat for reef‐associated species. A seascape ecology approach was applied to explore the associations between multiple scales of seascape structure and fish assemblage response variables within a small (49.6 km2) offshore no‐take MPA, Sir Bu Nair Island Protected Area, in Sharjah, United Arab Emirates. Fish–seascape associations were modelled with single regression trees. Both in situ and remote sensing–derived variables produced the best models with highest contributions from coral cover, amount of hard‐bottom habitat type and structural complexity of the seafloor terrain. Fish species richness was significantly higher where coral cover exceeded 35%. The hard‐bottom areas with coral supported diverse assemblages dominated by carnivorous and omnivorous fishes. The Sir Bu Nair Island Protected Area provides a critical refuge for threatened and regionally overexploited species including those with low resilience to fishing. The ecological success of this protected area is key to safeguarding regional marine biodiversity and recovering fish populations to enhance food security. [ABSTRACT FROM AUTHOR]

Summary: Neltuma ruscifolia, a neglected underutilised species (NUS) within the Fabaceae family, lacks formal commercial recognition, despite its nutritional richness and endemic status. The objective of this study was to evaluate the antioxidant and antiglycating properties, as well as to identify associated bioactive compounds, in extracts (ultrasound and agitation) of different grinding fractions of N. ruscifolia seeds. Bioactivity varied depending on the extraction procedure and milling fraction, with the highest value in ultrasound‐extracted residue (exocarp, mesocarp). Some additional polyphenolic compounds (like hydroxybenzoic/ellagic acids) only appeared upon ultrasound‐assisted extraction. It was possible to identify some polyphenols (such as chrysin, rutin, kaempferol and cinnamic, coumaric, protocatechuic, ellagic and caffeic acids) that were highly related to the bioactivity. The antioxidant, antiglycating, colourant and technological properties of the extracts different fractions of N. ruscifolia pods are mainly dependent on the selected milling fraction. The extraction method, in a second place, significantly affects the resulting quantity and the type of extracted compounds, defining their potential applications. [ABSTRACT FROM AUTHOR]

Fetal undernutrition establishes the foundations for hypertension development, with oxidative stress being a key hallmark. A growing interest in nutraceuticals for treating hypertension and environmental waste concerns prompted the present study aiming to evaluate whether supplementation with a polyphenol enriched extract from cocoa shell (CSE), a by‐product from the chocolate industry with antioxidant properties, reduces hypertension of developmental origin, thus improving mesenteric resistance artery (MRA) vasodilatation. Adult male and female offspring from rats exposed to 50% food restriction from mid‐gestation (maternal undernutrition, MUN) and controls were used. Supplementation was given through a gelatine (vehicle, VEH) or containing CSE (250 mg kg−1 day−1) 5 days week−1 for 3 weeks. Systolic blood pressure (SBP) was assessed by tail‐cuff plethysmography. MRA function was studied by wire myography, and superoxide anion and nitric oxide were investigated by fluorescent indicators and confocal microscopy. Compared to control‐VEH, MUN‐VEH males showed significantly higher SBP, reduced MRA as well as relaxation to ACh, sodium nitroprusside and the AMPK agonist 5‐aminoimidazole‐4‐carboxamide riboside, but not to isoproterenol. In MUN males, endothelial endothelium‐derived hyperpolarizing factor and nitric oxide were unaltered, but MRA released a vasoconstrictor prostanoid and produced higher levels of superoxide anion. CSE normalized blood pressure and improved all above‐mentioned MRA alterations in MUN males without an effect on control counterparts, except the reduction of superoxide anion. MUN‐VEH females were normotensive and only showed a tendency towards larger superoxide anion production, which was abolished by CSE. CSE supplementation reduces SBP improving endothelium‐dependent and independent MRA vasodilatation, related to local superoxide anion reduction, being a potential nutraceutical ingredient to counteract hypertension, in addition to contributing to the circular economy. Key points: Fetal undernutrition induces hypertension in males associated with deficient resistance artery vasodilatation, being normalized by cocoa shell extract (CSE).Release of a cyclooxygenase‐derived contractile factor is the main endothelial alteration, which is abolished by CSE.AMPK and soluble guanylyl cyclase‐mediated relaxation are also reduced in smooth muscle cells from maternal undernutrition resistance arteries, being improved by CSE.Vascular oxidative damage caused by excess superoxide anion generation can account for impaired vasodilatation, which is improved by CSE.The capacity of CSE to improve relaxation is probably related to its antioxidant bioactive factors, and thus cocoa shell is a potential food by‐product to treat hypertension. [ABSTRACT FROM AUTHOR]

Due to the difficult access of the electrolyte into the nanoconfined space of nanoporous reduced graphene oxide (rGO) electrodes, achieving the optimal electrochemical performance of these devices becomes a challenge. In this work, the dynamics of interfacial‐governed phenomena are investigated during a voltage‐controlled electrochemical activation of nanoporous rGO electrodes that leads to an enhanced electrochemical performance in terms of areal capacitance and electrochemical impedance. In situ/operando characterization techniques are used to reveal the dynamics of the irreversible material changes introduced during the activation process, including ionic diffusion and water confinement within the nanopores, along with the reduction of oxygenated groups and the decrease of the rGO interlayer distance. Furthermore, operando techniques are used to uncover the origin of the complex polarization‐dependent dynamic response of rGO electrodes. The study reveals that the reversible protonation/deprotonation of remaining functional groups and the cation electro‐adsorption/desorption process in the graphene basal plane govern the pseudocapacitive performance of nanoporous rGO electrodes. This work brings new understanding of the complex interplay between surface chemistry, ion confinement, and desolvation processes occurring during electrochemical cycling in nanoporous rGO electrodes, offering new insights for designing high‐performing electrodes based on nanoporous rGO. [ABSTRACT FROM AUTHOR]

This work presents a study of piezoelectric zinc oxide (ZnO) thin films deposited by a novel post‐reactive sputtering method. The process utilizes a rotating drum with DC magnetron sputtering deposition onto substrates with subsequent DC plasma‐assisted oxidation of the deposited metal to metal oxide. The paper analyzes the influence of plasmaassisted magnetron sputtering (PA‐MS) deposition parameters (O2 plasma source power, O2 flow, and Ar flow) on the morphological, structural, optical, and piezoelectric properties of ZnO thin films. Design of experiments has been utilized to evaluate the role of these parameters on the growth rate (rg) and the properties of resulting films. Results indicate a predominant influence of the plasma power on the rg over other parameters. Among the eight tested samples, three of them show high crystal quality with high intensity (0001) diffraction peak, characteristic of the wurtzite crystalline structure of ZnO, and one of them exhibits piezoelectric coefficient values of ≈11pC N−1. That sample corresponding to a ZnO film deposited at the lowest rg of 0.075 nm s−1, confirmed the key role of the deposition parameters on the piezoelectric response of films, and demonstrated PA‐MS as a promising technique to produce high‐quality piezoelectric thin films. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Parkinson disease (PD) is a complex and heterogeneous neurodegenerative disorder with a broad spectrum of clinical manifestations, determined by a complex interplay of environmental and genetic factors. This study aimed to investigate genetic variants associated with PD and assess their impact on the disease phenotype through genotype–phenotype correlations.We employed a targeted resequencing panel to analyze 27 genes linked to PD in a cohort of 1185 PD patients from southern Spain. Variants were categorized based on the American College of Medical Genetics and Genomics pathogenicity criteria. Demographic and clinical data were also collected.Among the patients analyzed, 13.5% carried potential disease‐causing pathogenic or likely pathogenic variants in 12 different genes, indicating significant genetic heterogeneity. The most frequently affected genes were LRRK2, PRKN, and GBA1 (accounting for 72.1% of positive cases). Sex‐specific differences were observed, with a higher proportion of female patients carrying LRRK2 variants. Differences in age at onset and clinical features were also observed among the different mutated genes. Notably, variants in genes associated with atypical parkinsonism presented distinct clinical presentations, highlighting the importance of genetic factors in the differential diagnosis.Our study provides valuable information on the genetic landscape of PD and its clinical manifestations. The observed genotype–phenotype correlations, along with sex‐specific differences, emphasize the complexity of PD pathogenesis, underlining the importance of personalized approaches to PD diagnosis and treatment. Further investigations into genetic interactions and population‐specific effects are warranted to enhance our understanding of PD etiology and improve patient care. [ABSTRACT FROM AUTHOR]

Fisher's general principle for sex allocation holds that population sex ratios are typically balanced because parents producing the rare sex are benefited and the rare sex alternates over time. In species that have temperature‐dependent sex determination (TSD), thermal reaction norms need to be adjusted at the population level to avoid extremely biased sex ratios and extinction. Extant species with TSD experienced drastic climatic changes in the geological past and must necessarily have mechanisms of adaptation. I propose here a conceptual framework to explain how TSD curves could be adjusted by means of natural selection, based on Fisher's equilibrium sex‐ratio principle. Through a process that alternatively favors mothers that tend to produce the rare sex under new temperatures, sex ratios eventually return toward a theoretical equilibrium. Prerequisites for this model are variability among mothers in the tendency to produce a particular sex at a given temperature (i.e., variability in the thermal reaction norm), inheritance of this trend, and higher fitness of the rare sex. This straightforward mechanism could facilitate thermal adaptation in species with TSD over multiple generations. [ABSTRACT FROM AUTHOR]

Background: Previous studies correlated Sensititre YeastOne and gradient diffusion plastic strips with standard procedures for the detection of echinocandin‐resistant C. glabrata isolates. However, these studies were limited by the low number of resistant isolates studied; the inclusion of sufficient numbers of mutant isolates is essential to test the procedures' capacity to detect resistance. Objective: We assessed the performance of Sensititre YeastOne and Etest strips to detect echinocandin resistance in susceptible or resistant C. glabrata isolates (n = 80) in which the FKS genes were sequenced, and MICs interpreted using EUCAST and CLSI breakpoints. Patients/Methods: Isolates were echinocandin‐susceptible (n = 50) or echinocandin‐resistant according to EUCAST 7.4 methodology. Echinocandin susceptibility using Sensititre YeastOne and Etest strips and categorical agreement were assessed. Results: All except one anidulafungin‐resistant isolate had an anidulafungin Sensititre YeastOne MIC ≥ 0.25 mg/L, while most micafungin‐resistant isolates had a MIC ≥ 0.25 mg/L. Likewise, all anidulafungin‐resistant isolates had an anidulafungin Etest strip‐obtained MIC ≥ 0.03 mg/L, whereas micafungin‐resistant isolates were ≥ 0.125 mg/L. Overall, these commercial methods correctly classified > 90% of isolates by using any breakpoint. Despite the low number of errors detected, these were mostly false resistance (major errors) with EUCAST breakpoints and false susceptibility (very major errors) with CLSI breakpoints. Conclusions: Sensititre YeastOne and Etest strips were suitable procedures to detect echinocandin resistance in C. glabrata. The high number of FKS mutants included reinforces our study and opens the door for multicentre validations. [ABSTRACT FROM AUTHOR]

Two‐component systems (TCSs) are vital signal transduction pathways ubiquitous among bacteria, facilitating their responses to diverse environmental stimuli. In Bacillus subtilis, the DesK histidine kinase thermosensor, together with the response regulator DesR, constitute a TCS dedicated to membrane lipid homeostasis maintenance. This TCS orchestrates the transcriptional regulation of the des gene, encoding the sole desaturase in these bacteria, Δ5‐Des. Additionally, B. subtilis possesses a paralog TCS, YvfT/YvfU, with unknown target gene(s). In this work, we show that YvfT/YvfU controls the expression of the yvfRS operon that codes for an ABC transporter. Interestingly, we found that this regulation also involves the action of DesK/DesR. Notably, opposite to des, yvfRS transcription is induced at 37°C and not at 25°C. Our in vivo and in vitro experiments demonstrate that both YvfU and DesR directly bind to the operon promoter region, with DesR exerting its control over yvfRS expression in its unphosphorylated state. Our study uncovers an intriguing case of cross‐regulation where two homologous TCSs interact closely to finely tune gene expression in response to environmental cues. These findings shed light on the complexity of bacterial signal transduction systems and their critical role in bacterial adaptability. [ABSTRACT FROM AUTHOR]

Objective: Limited evidence exists regarding the impact of the COVID‐19 pandemic on the onset and trajectory of eating disorders (EDs) among young in Spain. This study aims to analyze the characteristics and recent trends in hospital admissions for EDs within the pediatric population. Methods: A retrospective analysis was conducted on hospital admissions for EDs among patients aged 10–19 years between 2016 and 2022. The main outcomes examined included hospital rates (overall, stratified by ED type and age group), psychiatric comorbidities, and length of stay. Results: A total of 8275 hospitalizations due to EDs were identified, constituting 1 in 6 hospital admissions for mental illness and behavioral disorders. Predominant characteristics of this population included female sex (93%), aged 15–19 years (58.3%), admission primarily for anorexia nervosa (71.6%), and psychiatric comorbidity (35.6%). Hospital admissions for EDs in the pediatric population showed an increasing trend, with an annual average increase of 11.1% (95% CI: 2.6, 22.6). This rise was led by children aged 10–14 years, with a yearly increase in EDs hospitalization rates of 28.4% (95% CI: 13.5, 56.3) since 2019. Each discharge related to EDs was associated with a median stay of 24 days (IQR: 10, 40). Discussion: Efforts in community healthcare should prioritize early detection and intervention for symptoms indicative of EDs in the pediatric population, aiming to mitigate the severity of cases requiring hospitalization. These findings underscore the necessity for targeted health planning policies to address the growing burden of EDs among Spanish youth. [ABSTRACT FROM AUTHOR]

Background: The misuse of psychotropic medication has increased during the past decade, especially among adolescents. The aim of our study was to describe the prevalence and patterns of the nonmedical use of benzodiazepines (BDZ) and Z‐hypnotics among school‐aged adolescents through the lens of sex. In addition, we sought to analyze the temporal evolution of the nonmedical use of these drugs during the period 2016–2021. Methods: The temporal evolution of the nonmedical use of these drugs was analyzed based on survey data collected in 2016, 2018 and 2021, which includes the first years of the COVID‐19 pandemic. To assess the possible effect of the COVID‐19 pandemic, the year at survey was conducted was introduced as a categorical variable. We used data from the Spanish State Survey on Drug Use in Secondary Education, which covers drug use among students aged 14–18 years. Using multivariate logistic regression models, we estimated the independent effect of different variables (sociodemographic data, use of other psychoactive substances, risk perception and availability) on the nonmedical use of BDZ and Z‐hypnotics. Results: In total, survey data from 95,700 adolescents were included in our analysis. The nonmedical use of BDZ and Z‐hypnotics increased among adolescents during the study period. The adjusted odds ratio (AOR) from 2016 to 2018 was 1.11 (95% CI 0.94–1.31) and from 2018 to 2021 the AOR was 1.26 (95% CI 1.08–1.46), using 2016 and 2018, respectively, as reference years. The nonmedical use of BDZ and Z‐hypnotics was more likely in adolescent girls than boys (AOR = 2.11). The nonmedical use of prescription opioids (AOR = 3.44), novel psychoactive substances and other illicit psychoactive drugs (AOR = 4.10) were risk factors for the nonmedical use of BDZ and Z‐hypnotics in both sexes. Use of cannabis (AOR = 1.38) was a predictor of nonmedical use in female adolescents only. Conclusions: This study shows that the trend of the nonmedical use of BDZ and Z‐hypnotics among school‐aged adolescents in Spain increased between 2016 and 2021. Among adolescents aged 14 to 18, the probability of nonmedical use of these psychoactive substances was twice as high for female adolescents as for male adolescents. [ABSTRACT FROM AUTHOR]

Objective: Obstetric forceps play an important role in safe childbirth, yet there is a lack of distinction between various forceps types in clinical practice. This study aimed to evaluate and compare perineal pressure and forces on the baby during nonrotational forceps‐assisted births using Simpson‐Braun forceps, Kielland forceps, and Thierry spatulas on a simulation model. Methods: This experimental study involved six obstetricians conducting 108 forceps‐assisted births on a simulation model. Instruments were assessed for their impact on perineal pressure, traction force, and operator‐assessed difficulty. Results: Thierry's spatulas exerted the lowest force on the baby, while Kielland forceps exhibited the lowest perineal pressure, though not statistically significant. An experienced obstetrician demonstrated less perineal pressure with Simpson forceps. Notably, no significant differences in difficulty were observed between instruments. Conclusion: This study highlights distinctions in forceps performance, with Thierry spatulas applying the least force on the fetal head, while an experienced obstetrician fared better with Simpson forceps in terms of perineal pressure. Kielland forceps remain a viable alternative for nonrotational forceps births, showing comparable outcomes. Synopsis: Thierry spatulas are gentlest on the fetal head, Simpson forceps are favored by experienced obstetricians for perineal pressure, and Kielland forceps offer an alternative with similar outcomes. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The Alzheimer's Prevention Initiative (API) Generation Studies evaluated the BACE inhibitor umibecestat for Alzheimer's disease (AD) prevention. The studies were terminated early, and the reversibility of umibecestat's side effects was assessed. METHODS: Cognitively unimpaired 60‐ to 75‐year‐old apolipoprotein E (APOE) ε4 homozygotes and heterozygotes (the latter with elevated brain amyloid deposition) (n = 1556) received umibecestat (50 or 15 mg daily) or placebo for 7 months on average and were followed for a median (interquartile range) of 4 (3 to 6) months after washout. RESULTS: Compared to placebo, umibecestat‐treated participants had small, non‐progressive, but statistically significant decline in performance on certain cognitive batteries including Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and API Preclinical Composite Cognitive test, but not Clinical Dementia Rating‐Sum of Boxes. RBANS differences were no longer significant at the end of follow‐up. DISCUSSION: In people at genetic risk for AD, high‐dose beta‐site amyloid precursor protein cleaving enzyme (BACE) inhibition was associated with early mild cognitive worsening, which reversed shortly after washout, suggesting a symptomatic side effect not associated with neurodegeneration. Fully anonymized data, images, and samples are available upon request for further research on BACE inhibition. Highlights: This is the first trial with blinded assessment of reversibility of BACE inhibitor side effects.Umibecestat was tested in cognitively unimpaired persons at genetic risk for AD.Umibecestat led to early mild cognitive decline that reversed shortly after washout.This suggests a potentially manageable effect not associated with neurodegeneration.Further research may determine the future of BACE inhibition in AD prevention. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Understanding the impact of biomarker‐based dementia risk estimation in people with mild cognitive impairment (MCI) and their care partners is critical for patient care. METHODS: MCI patients and study partners were counseled on Alzheimer's disease (AD) biomarker and dementia risk was disclosed. Data on mood, quality of life (QoL), and satisfaction with life (SwL) were obtained 1 week and 3 months after disclosure. RESULTS: Seventy‐five dyads were enrolled, and two‐thirds of the patients opted for biomarker testing. None of the participants experienced clinically relevant depression or anxiety after disclosure. All dyads reported moderate to high QoL and SwL throughout the study. Patients reported more subthreshold depressive symptoms 1 week and lower QoL and SwL 3 months after disclosure. In patients, depression (odds ratio [OR]: 0.76) and anxiety (OR: 0.81) were significant predictors for the decision against biomarker testing. DISCUSSION: No major psychological harm is to be expected in MCI patients and care partners after dementia risk disclosure. TRIAL REGISTRATION: This study is registered in the German clinical trials register (Deutsches Register Klinischer Studien, DRKS): http://www.drks.de/DRKS00011155, DRKS registration number: DRKS00011155, date of registration: 18.08.2017. Highlights: Patients with mild cognitive impairment (MCI) and study partners were counseled on Alzheimer's disease (AD) biomarker‐based dementia risk estimation.About two‐thirds of patients opted for biomarker testing and received their dementia risk based on their AD biomarker status.Patients who decided in favor or against CSF biomarker testing differed in psychological features.We did not observe major psychological harm after the dementia risk disclosure.Coping strategies were associated with better subsequent mood and well‐being in all participants. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a widespread environmental contaminant with high toxicity to human health. Melatonin has been shown to improve Cd‐induced liver damage. However, its mechanism has not yet been elucidated. In this study, we aimed to investigate the effects of melatonin on Cd‐induced liver damage and fibrosis. A combination of 16S rRNA gene sequencing and mass spectrometry‐based metabolomics was adopted to investigate changes in the gut microbiome and its metabolites on the regulation of melatonin in Cd‐induced liver injury and fibrosis of mice. Further, nonabsorbable antibiotics, a fecal microbiota transplantation (FMT) program and intestine‐specific farnesoid X receptor (FXR) knockout mice were employed to explore the mechanism of melatonin (MT) on liver injury and fibrosis in Cd treated mice. MT significantly improved hepatic inflammation, bile duct hyperplasia, liver damage, and liver fibrosis, with a notable decrease in liver bile acid levels in Cd‐exposed mice. MT treatment remodeled the gut microbiota, improved gut barrier function, and reduced the production of gut‐derived lipopolysaccharide (LPS). MT significantly decreased the intestinal tauro‐β‐muricholic acid levels, which are known as FXR antagonists. Notably, MT prominently activated the intestinal FXR signaling, subsequently inhibiting liver bile acid synthesis and decreasing hepatic inflammation in Cd‐exposed mice. However, MT could not ameliorate Cd‐induced liver damage and fibrosis in Abx‐treated mice. Conversely, MT still exerted a protective effect on Cd‐induced liver damage and fibrosis in FMT mice. Interestingly, MT failed to reverse liver damage and fibrosis in Cd‐exposed intestinal epithelial cell‐specific FXR gene knockout mice, indicating that intestinal FXR signaling mediated the protective effect of MT treatment. MT improves Cd‐induced liver damage and fibrosis through reshaping the intestinal flora, activating the intestinal FXR‐mediated suppression of liver bile acid synthesis and reducing LPS leakage in mice. [ABSTRACT FROM AUTHOR]

Haploidentical haematopoietic stem cell transplantation (haplo‐HSCT) is one of the most effective therapies for treating malignant haematological disorders. However, HLA disparities are significant barriers to the success of this process since they increase the risk of graft versus host disease (GvHD). HLA disparities quantification could help to anticipate the probability and degree of GvHD, but the best tool for such quantification remains a challenge. The aim of this study was to quantify the degree of HLA epitope incompatibilities using PIRCHE (Predicted Indirectly Recognisable HLA Epitopes) algorithm for immunogenicity prediction and their potential relationship with GvHD degree and clinical outcome. We studied 145 patients who underwent a haplo‐HSCT with post‐transplant cyclophosphamide (PTCy) from a related donor between 2013 and 2020 at our centre evaluating molecular HLA mismatches by PIRCHE‐algorithm. Patients with PIRCHE Score (PS) I + II > 38 in GvH direction, developed acute GvHD grade II–IV earlier than their counterparts (HR: 1.71, 95% CI: 1.02–2.87, p = 0.032). In addition, PS‐B > 1 in GvH direction was an independent risk factor for chronic GvHD, (HR: 2.51, 95% CI 1.17–5.36, p = 0.017). A higher incidence of relapse was found for patients with PS‐II > 28 HvG (HR: 9.16, 95% CI: 2.47–33.92, p < 0.001) which also favoured a worse GvHD/relapse‐free survival in patients with PS‐II > 27 in HvG direction (HR: 1.88, 95% CI: 1.11–3.18, p = 0.017). These findings indicate that the alloreactivity inferred by epitope HLA disparities is associated with post‐transplant outcomes. Thus, analysing PS could benefit the selection of the most suitable donors allowing patient stratification based on HLA mismatches in the context of haplo‐HSCT with PTCy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Truffle cultivation is evolving rapidly and new agronomic practices such as 'truffle nests' (localized peat amendments of the orchard soil) are being developed. Truffle nests improve the shape of truffles and their depth in the soil and reduce the occurrence of insect damage but have also raised concerns about their impact on the ripeness and maturity of the harvested truffles. In this study, the effect of the nests on the volatile organic compounds profile and the aromatic profile of black truffles was evaluated, as well as the existence of perceptible sensorial differences in truffles. For this, truffles growing in nests were compared with truffles growing in the bulk soil of the same host tree. RESULTS: Gas chromatography showed that nest truffles had a less complex volatile organic compound profile than bulk‐soil truffles. Olfactometry indicated that nest truffles were associated with higher modified frequency values of odorants corresponding to sulfur‐containing compounds. Despite this, sensory evaluation with consumers could not clearly show that nest truffles can be distinguished sensorially from bulk‐soil truffles. CONCLUSION: The results prove that soil conditions can influence the aromatic profile of truffles and thus suggest the possibility of managing truffle aroma using agronomic practices. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Selecting a good mate is a decision with important fitness consequences. For this reason, mate choice has promoted the evolution of sexual ornaments signaling the quality of an individual. In fossorial animals, inhabiting visually restricted underground environments, chemical senses should be very important for mate choice. We examined whether sexual chemical signals (substrate scent marks) produced by males of the Iberian worm lizard, Blanus cinereus, a strictly fossorial blind amphisbaenian, provide information to females on morphological traits and health state. We administered corticosterone (CORT) to males simulating a continuous stressor affecting their health. Females preferred settling at sites scent‐marked by males in comparison with similar sites with female scent or unmarked sites, but the attractiveness of males' scent differed between individuals. Females preferred scent marks of larger/older males and with a higher immune response, while their body condition and CORT treatment were unrelated to female preferences. Chemical analyses showed that proportions of some compounds in precloacal secretions of males (used to produce scent marks) were correlated with the morphological (body size) and health state (immune response and body condition, but not CORT treatment) of these males. These results suggest that females may make site‐selection decisions based on assessing the chemical characteristics of males' scent marks, which were reliably related to some of the traits of the male that produced the scent. Therefore, females might use chemical senses to increase the opportunities to find and mate with males of high quality, coping with the restrictions of the subterranean environment. [ABSTRACT FROM AUTHOR]

In this article, we compile and characterize a total of 43 collaborative web map projects by a set of parameters that enable the understanding and comparability of current and future projects. We then develop a comprehensive methodological framework to explore volunteered geographic information (VGI) and spatial data infrastructure (SDI) convergence based on this review. The main results show the dominance of citizen science projects, followed by initiatives promoting sustainability values, local development, and governance. Although values remain low, the potential to achieve convergence in VGI–SDI features is very high in citizen science projects, where the presence of experts and the funding of these projects by governments and decision‐making entities enable quality standards in the collection and distribution of the contributed information. The work concludes by addressing two major challenges facing current VGI projects: firstly, accessing affordable technological solutions that allow the creation of collaborative web maps with SDI‐like functions. Secondly, guaranteeing the project's sustainability and the preservation of the information gathered. [ABSTRACT FROM AUTHOR]

The aim of the current study is to demonstrate the feasibility of radiofrequency (RF) pulses generated via an optimal control (OC) algorithm to perform magnetic resonance elastography (MRE) and quantify the mechanical properties of materials with very short transverse relaxation times (T2 < 5 ms) for the first time. OC theory applied to MRE provides RF pulses that bring isochromats from the equilibrium state to a fixed target state, which corresponds to the phase pattern of a conventional MRE acquisition. Such RF pulses applied with a constant gradient allow to simultaneously perform slice selection and motion encoding in the slice direction. Unlike conventional MRE, no additional motion‐encoding gradients (MEGs) are needed, enabling shorter echo times. OC pulses were implemented both in turbo spin echo (OC rapid acquisition with refocused echoes [RARE]) and ultrashort echo time (OC UTE) sequences to compare their motion‐encoding efficiency with the conventional MEG encoding (classical MEG MRE). MRE experiments were carried out on agar phantoms with very short T2 values and on an ex vivo bovine tendon. Magnitude images, wave field images, phase‐to‐noise ratio (PNR), and shear storage modulus maps were compared between OC RARE, OC UTE, and classical MEG MRE in samples with different T2 values. Shear storage modulus values of the agar phantoms were in agreement with values found in the literature, and that of the bovine tendon was corroborated with rheometry measurements. Only the OC sequences could encode motion in very short T2 samples, and only OC UTE sequences yielded magnitude images enabling proper visualization of short T2 samples and tissues. The OC UTE sequence produced the best PNRs, demonstrating its ability to perform anatomical and mechanical characterization. Its success warrants in vivo confirmation in further studies. [ABSTRACT FROM AUTHOR]

Background: Halitosis in children implies psychosocial repercussions. Risk factors associated with this condition are unclear, and detection methods are inaccurate. Aim: To quantify the levels of sulfur‐like compounds in children with asthma and healthy children from a novel validated assay, and to establish the risk factors related to halitosis. Design: One hundred and twenty‐eight individuals (63 healthy and 65 asthmatic) from 3 to 17 years of age were tested using a passive colorimetric sensor to measure the levels of sulfur‐like compounds in breath and saliva. Information was collected on oral hygiene habits, gingival and dental health, breathing type, and dental malocclusion. Results: The mean values of hydrogen sulfide were 4.0 ± 6.8 and 19.7 ± 12.2 ppbv (parts per billion in volume) in the control and asthmatic groups, respectively (p <.001). The presence of higher concentrations of sulfur compounds was significantly associated (p <.05) with the presence of gingival inflammation, tongue coating, dental plaque, mouth breathing, hypomineralization, age, tongue brushing, and the use of dental floss. Conclusion: The level of sulfur in breath and saliva was significantly higher in patients with asthma. These results can serve as a precedent to raise awareness among paediatricians and parents about oral hygiene care in children and adolescents. [ABSTRACT FROM AUTHOR]

Background: Asthma pathology may induce changes in naïve/memory lymphocyte proportions assessable through the evaluation of surface CD26 (dipeptidyl peptidase 4/DPP4) levels. Our aim was to investigate the association of asthma phenotype/severity with the relative frequency of CD26−/lo, CD26int and CD26hi subsets within different lymphocyte populations. Methods: The proportion of CD26−/lo, CD26int and CD26hi subsets within CD4+ effector T cells (Teff), total CD4− lymphocytes, γδ‐T cells, NK cells and NKT cells was measured in peripheral blood samples from healthy (N = 30) and asthma (N = 119) donors with different phenotypes/severities by flow cytometry. We performed K‐means clustering analysis and further characterised the CD4+CD26−/lo Teff cell subset by LC–MS/MS and immunofluorescence. Results: Cluster analysis including clinical and flow cytometry data resulted in four groups, two of them with opposite inflammatory profiles (neutrophilic vs. eosinophilic). Neutrophilic asthma presented reduced CD4−CD26hi cells, which negatively correlated with systemic inflammation. Eosinophilic asthma displayed a general expansion of CD26−/lo subsets. Specifically, CD4+CD26−/lo Teff expansion was confirmed in asthma, especially in atopic patients. Proteomic characterisation of this subset with a TEM/TEMRA phenotype revealed upregulated levels of innate (e.g. MPO and RNASE2) and cytoskeleton/extracellular matrix (e.g. MMP9 and ACTN1) proteins. Immunofluorescence assays confirmed the presence of atypical proteins for CD4+ T cells, and an enrichment in 'flower‐like' nuclei and MMP9/RNASE2 levels in CD4+CD26−/lo Teff compared to CD4+ T lymphocytes. Conclusion: There is an association between CD26 levels in different lymphocyte subsets and asthma phenotype/severity. CD4+CD26−/loTEMRA cells expressing innate proteins specific to eosinophils/neutrophils could be determinant in sustaining long‐term inflammation in adult allergic asthma. [ABSTRACT FROM AUTHOR]