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Saline shallow lakes may play an important role in carbon exchange with the atmosphere, but their alteration may change carbon balance and greenhouse gas emissions patterns. This study investigated the relationship between carbon metabolic processes and environmental factors, focusing on alterations in salinity, hydroperiod length, and trophic status. The results revealed that disruptions to natural salinity patterns, driven by hydrological changes and ecological degradation, enhanced carbon greenhouse gas emitting metabolisms. In contrast, well-preserved lakes demonstrated significantly higher carbon retention and climate mitigation capacities (-188 ± 412 g C m -2  yr -1 ) compared to lakes with hydrological and trophic disturbances (-30 ± 141 g C m -2  yr -1 ). These findings emphasize the relevance of the metabolic activity of saline shallow lakes and highlight the need for targeted management and restoration efforts to maximize their climate regulation potential. The insights gained from this study may also be applicable to similar ecosystems in other regions., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Glioblastoma (GB) is an aggressive malignant central nervous system tumor that is currently incurable. One of the main pitfalls of GB treatment is resistance to the chemotherapeutic standard of care, temozolomide (TMZ). The role of aldehyde dehydrogenases (ALDHs) in the glioma stem cell (GSC) subpopulation has been related to chemoresistance. ALDHs take part in processes such as cell proliferation, differentiation, invasiveness or metastasis and have been studied as pharmacological targets in cancer treatment. In the present work, three novel α,β-acetylenic amino thiolester compounds, with demonstrated efficacy as ALDH inhibitors, were tested in vitro on a panel of six human GB cell lines and one murine GB cell line. Firstly, the expression of the ALDH1A isoforms was assessed, and then inhibitors were tested for their cytotoxicity and their ability to inhibit cellular ALDH activity. Drug combination assays with TMZ were performed, as well as an assessment of the cell death mechanism and generation of ROS. A knockout of several ALDH genes was carried out in one of the human GB cell lines, allowing us to discuss their role in cell proliferation, migration capacity and resistance to treatment. Our results strongly suggest that ALDH inhibitors could be an interesting approach in the treatment of GB, with EC50 values in the order of micromolar, decreasing ALDH activity in GB cell lines to 40-50%.

Objective: To determine the perceptions of persons with tuberculosis (TB) and health workers on Care TB - a mobile application for the community-led monitoring (CLM) of TB services., Methods: We used a qualitative research method. Six people with tuberculosis and ten health workers were chosen through purposive sampling for semi-structured interviews. The narrative data produced from the interviews were subjected to qualitative content analysis in order to uncover salient themes and patterns., Results: The community-led monitoring mobile application was shown to be acceptable both to TB healthcare providers and patients. It enhances information access and streamlines the process of reporting care barriers. The application also allows persons with TB to interact with one another, potentially eliminating stigma and discrimination. Potential challenges to implementing the CLM program include issues with internet connectivity, costs, and human resources., Conclusion: This study provides preliminary evidence of the acceptability and perceived feasibility of a mobile application for the community-led monitoring of TB services. For the CLM initiative to be scaled up across the country, more financial and technical support is required., Competing Interests: All authors declared no conflicts of interest. The sponsors/funders had no role in the design, execution, interpretation, or writing of the study., (© 2024 Acta Medica Philippina.)

The current work aimed to identify genomic regions and candidate genes associated with resilience in pigs. In previous work, we proposed the body weight deviation from the expected growth curve (ΔBW) and the increase of the positive acute-phase protein haptoglobin (ΔHP) after a vaccine challenge as resilience indicators which may be improved through selective breeding in pigs. Individuals with steady growth rate and minor activation of haptoglobin (high ΔBW and low ΔHP values) were considered resilient. In contrast, pigs with perturbed growth rate and high activation of haptoglobin (low ΔBW and high ΔHP values) were considered susceptible. Both ∆BW and ∆HP were simultaneously considered to select the most resilient (N = 40) and susceptible (N = 40) pigs. A genome-wide association study was carried out for the pigs' response classification to the challenge test using whole-genome sequence data (7,760,720 variants). Eleven associated genomic regions were identified, harbouring relevant candidate genes related to the immune response (such as pro- and anti-inflammatory responses) and growth pathways. These associated genomic regions harboured 41 potential functional mutations (frameshift, splice donor, splice acceptor, start loss and stop loss/gain) in candidate genes. Overall, this study advances our knowledge about the genetic determinism of resilience, highlighting its polygenic nature and strong relationship with immunity and growth., (© 2024 The Author(s). Journal of Animal Breeding and Genetics published by John Wiley & Sons Ltd.)

Nanoparticles (NPs) are receiving increasing interest in biomedical applications. However, due to their large surface area, in physiological environments, they tend to interact with plasma proteins, inducing their agglomeration and ultimately resulting in a substantial efficiency decrease in diagnostic and therapeutic applications. To overcome such problems, NPs are typically coated with a layer of hydrophilic and biocompatible polymers, such as PEG chains. However, few examples exist in which this property could be systematically fine-tuned and combined with added properties, such as emission. Herein, we report a novel mussel-inspired catechol-based strategy to obtain biocompatible and multifunctional coatings, using a previously developed polymerization methodology based on the formation of disulfide bridges under mild oxidative conditions. Two families of NPs were selected as the proof of concept: mesoporous silica NPs (MSNPs), due to their stability and known applications, and magnetite NPs (Fe 3 O 4 NPs), due to their small size (<10 nm) and magnetic properties. The PEG coating confers biocompatibility on the NPs and can be further functionalized with bioactive molecules, such as glucose units, through the end carboxylic acid moieties. Once we demonstrated the feasibility of our approach to obtaining PEG-based coatings on different families of NPs, we also obtained multifunctional coatings by incorporating fluorescein functionalities. The resulting coatings not only confer biocompatibility and excellent cell internalization, but also allow for the imaging and tracking of NPs within cells.

Colloidal quantum dots (cQDs), semiconductor materials with widely tunable properties, can be printed in submicrometer patterns through electrohydrodynamic printing, avoiding aggressive photolithography steps. Postprinting ligand exchange determines the final optoelectronic properties of the cQD structures. However, achieving a complete bulk exchange is challenging, and the conventional vibrational analysis lacks the required spatial resolution. Infrared nanospectroscopy enables quantitative analysis of vibrational signals and structural topography on the nanometer scale upon ligand substitution on lead sulfide cQDs. A solution of ethanedithiol led to rapid (∼60 s) exchange of ≤90% of the ligands, in structures up to ∼750 nm thick. Prolonged exposures (>1 h) caused the degradation of the microstructures, with a systematic removal of cQDs regulated by surface:bulk ratios and solvent interactions. This study establishes a method for the development of devices through a combination of tunable photoactive materials, additive manufacturing of microstructures, and their quantitative nanometer-scale analysis.

Background: Amyloidosis can affect the heart, causing arrhythmia, thromboembolic events, and sudden cardiac death. Coronary sinus thrombosis is an uncommon though life-threatening condition which requires early identification and management., Case Summary: A 72-year-old Caucasian man, who recovered from out-of-hospital cardiorespiratory arrest, was diagnosed with coronary sinus thrombosis using cardiac imaging techniques. He had no history of invasive procedures and was diagnosed with cardiac amyloidosis based on an extra-cardiac biopsy positive for light chain amyloid, with consistent clinical, echocardiographic, and magnetic resonance criteria., Discussion: A high frequency of intracardiac thrombosis is seen in amyloidosis. However, coronary sinus thrombosis is an uncommon complication. A multimodality imaging approach appears to be useful for the early diagnosis of coronary sinus thrombosis. The low specificity of the clinical signs, as well as the fast impairment of the patients, could result in fatal complications such as acute myocardial infarction, arrhythmia, and sudden death. Early screening, particularly in high-risk patients, as well as the use of early anticoagulant therapy, could reduce the associated morbidity and mortality., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most challenging viral diseases that cause substantial economic losses in the pig industry worldwide. The clinical signs of PRRS depend on, among others, the immunomodulatory properties of the PRRS virus strain, farm health status, herd immunity, and host genetics. The high virulence and mutation rate of PRRS virus limit the efficacy of vaccination programs. In recent years, several candidate genetic markers associated with PRRS resilience have been identified, and selective breeding was suggested as an additional approach to control PRRS under field conditions. Even so, it is essential to investigate the effects of these genetic markers on pigs' productivity. Our study aimed to assess the association between seven previously reported candidate genetic markers for host response to PRRS (rs80800372 in GBP1, rs340943904 in GBP5, rs322187731 in GBP6, rs1107556229 in CD163, rs338508371 in SGK1, rs80928141 in TAP1, and a 275-bp insertion in the promoter of MX1) and production traits in pigs under non-challenging conditions., Results: About 600 high-health Duroc pigs were genotyped for the selected genetic markers and their effects on production traits (live body weight, carcass weight, backfat thickness, intramuscular fat content and composition) were assessed using a linear model. The genetic markers GBP5&#95;rs340943904, GBP6&#95;rs322187731, CD163&#95;rs1107556229, and the 275-bp insertion at the promoter of MX1 showed no relevant associations with growth and carcass traits at slaughter. Regarding GBP1&#95;rs80800372 (WUR1000125), the favourable G allele for PRRS resilience displayed significant additive effects on backfat thickness (+ 1.18 ± 0.42 mm; p = 0.005) and lean content (-1.72 ± 0.56%; p ≤ 0.01) at slaughter. In addition, the genetic markers SGK1&#95;rs338508371 and TAP1&#95;rs8092814 were associated with the palmitoleic content in gluteus medius, without affecting the total of the monounsaturated fatty acids., Conclusions: Our results indicate that genetic markers for PRRS resilience have no relevant effects on growth and carcass traits in pigs reared under non-challenging conditions, except for GBP1&#95;rs80800372 where the favourable allele for PRRS response has a negative impact on lean content. Therefore, since the effects of GBP1&#95;rs80800372 were attributed to the causal variant GBP5&#95;rs340943904, it seems beneficial to select pigs for the genetic marker at GBP5 instead of GBP1. Overall, pigs might be selected for enhanced PRRS resilience without compromising their overall productivity., (© 2024. The Author(s).)

Nowadays, indoor air quality monitoring has become an issue of great importance, especially in industrial spaces and laboratories where materials are handled that may release particles into the air that are harmful to health. This study focuses on the monitoring of air quality and particle concentration using low-cost sensors (LCSs). To carry out this work, particulate matter (PM) monitoring sensors were used, in controlled conditions, specifically focusing on particle classifications with PM2.5 and PM10 diameters: the Nova SDS011, the Sensirion SEN54, the DFRobot SEN0460, and the Sensirion SPS30, for which an adapted environmental chamber was built, and gaged using the Temtop M2000 2nd as a reference sensor (SRef). The main objective was to preliminarily assess the performance of the sensors, to select the most suitable ones for future research and their possible use in different work environments. The monitoring of PM2.5 and PM10 particles is essential to ensure the health of workers and avoid possible illnesses. This study is based on the comparison of the selected LCS with the SRef and the results of the comparison based on statistics. The results showed variations in the precision and accuracy of the LCS as opposed to the SRef. Additionally, it was found that the Sensirion SEN54 was the most suitable and valuable tool to be used to maintain a safe working environment and would contribute significantly to the protection of the workers' health.

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Amino acids (AAs) are modular building blocks which nature uses to synthesize both macromolecules, such as proteins, and small molecule natural products, such as alkaloids and non-ribosomal peptides. While the 20 main proteinogenic AAs display relatively limited side chain diversity, a wide range of non-canonical amino acids (ncAAs) exist that are not used by the ribosome for protein synthesis, but contain a broad array of structural features and functional groups. In this communication, we report the discovery of the biosynthetic pathway for a new ncAA, pazamine, which contains a cyclopropane ring formed in two steps. In the first step, a chlorine is added onto the C 4 position of lysine by a radical halogenase, PazA. The cyclopropane ring is then formed in the next step by a pyridoxal-5'-phosphate-dependent enzyme, PazB, via an S N 2-like attack at C 4 to eliminate chloride. Genetic studies of this pathway in the native host, Pseudomonas azotoformans, show that pazamine potentially inhibits ethylene biosynthesis in growing plants based on alterations in the root phenotype of Arabidopsis thaliana seedlings. We further show that PazB can be utilized to make an alternative cyclobutane-containing AA. These discoveries may lead to advances in biocatalytic production of specialty chemicals and agricultural biotechnology., (© 2024 Wiley-VCH GmbH.)

Among the symptoms presented by patients with SARS-Cov-2 infection, we can find various otorhinolaryngological alterations. Dysphonia appears in up to 79% of infected patients during the acute phase. Dysphonia can also occur as a sequelae, often underestimated, possibly due to its appearance along with other symptoms, also in patients after prolonged intubation or tracheostomy. We present a systematic review of the literature with a bibliographic search in PubMed, Cochrane and Google Scholar, with MESH terms including studies in English and Spanish. The results of the studies found and the vocal manifestations in patients during COVID-19 disease and the consequences produced are analysed. Dysphonia is an acute manifestation of COVID-19 with alterations in aerodynamic and acoustic analysis and in fibrolaryngoscopy. Post-COVID dysphonia can be a persistent symptom that is often underestimated, requiring multidisciplinary management and speech therapy intervention. Laryngeal sequelae are common in post-intubation or post-tracheostomy patients and are related to intubation time, tube number, pronation and respiratory sequelae., (Copyright © 2024 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Published by Elsevier España, S.L.U. All rights reserved.)

Maturity status and relative age are two of the determining factors in talent development. The aim of the study was to analyze the influence of biological maturity status and relative age on physical performance in young male and female handball players. The sample included 48 males (14.11 ± 1.17 years) and 41 females (14.25 ± 1.64 years) players from one Spanish professional handball academy. Anthropometric data (height, sitting height, body mass and self-reported biological parent heights) and physical performance data (CMJ, DJ, 20 m speed, T-test and throwing velocity) were collected. Biological maturity status was determined as the percentage of predicted adult height, while relative age was estimated in birth quartiles based on biennial age grouping (Q1-Q8). The results showed a positive correlation between maturity status and CMJ in male players ( p < 0.01). Differences in CMJ performance according to maturity status were identified ( p < 0.05), with higher jump heights being recorded especially in early maturing boys ( p < 0.01) and first lines and wings ( p < 0.05). The variance in CMJ test scores could be explained by the maturity status by 42.90% in U-15 ( p < 0.05) and 72.60% in U-16 male players ( p < 0.001). By contrast, no differences were found in girls ( p > 0.05). Moreover, no relationships were found between relative age and indices of physical performance ( p > 0.05). Overall, maturity status had greater impacts on the tests of physical performance than relative age. Stakeholders should monitor the maturity status of young handball players to avoid physical performance biases that do not allow them to develop their sporting potential., Competing Interests: The authors declare no conflict of interest, (Copyright © Institute of Sport – National Research Instutite.)

Osteoporosis is a chronic disease characterized by reduced bone mass and increased fracture risk, estimated to affect over 10 million people in the United States alone. Drugs used to treat bone loss often come with significant limitations and/or long-term safety concerns. Proteoglycan-4 (PRG4, also known as lubricin) is a mucin-like glycoprotein best known for its boundary lubricating function of articular cartilage. In more recent years, it has been shown that PRG4 has anti-inflammatory properties, contributes to the maintenance of subchondral bone integrity, and patients with PRG4 mutations are osteopenic. However, it remains unknown how PRG4 impacts mechanical and material properties of bone. Therefore, our objective was to perform a phenotyping study of bone in a Prg4 gene trap (GT) mouse (PRG4 deficient). We found that femurs of Prg4 GT mice have altered mechanical, structural, and material properties relative to wildtype littermates. Additionally, Prg4 GT mice have a greater number of calvarial osteoclasts than wildtype mice, but do not have a notable inflammatory serum profile. Finally, Prg4 GT mice do not have an altered rate of bone formation, and exogenous recombinant human PRG4 (rhPRG4) administration inhibited osteoclastogenesis in vitro, suggesting that the skeletal phenotype may be due to changes in bone resorption. Overall, this work demonstrates that PRG4 deficiency affects several integral properties of bone structure, mechanics, and skeletal cell activity, and provides the foundation and insight toward future work evaluating PRG4 as a potential therapeutic target in treating bone loss., (© 2023 Orthopaedic Research Society.)

Infection diseases are a major threat to global public health, with nosocomial infections being of particular concern. In this context, antimicrobial coatings emerge as a promising prophylactic strategy to reduce the transmission of pathogens and control infections. Here, antimicrobial door handle covers to prevent cross-contamination are prepared by incorporating iodine-loaded UiO-66 microparticles into a potentially biodegradable polyurethane polymer (Baycusan eco E 1000). These covers incorporate MOF particles that serve as both storage reservoirs and delivery systems for the biocidal iodine. Under realistic touching conditions, the door handle covers completely inhibit the transmission of Gram-positive bacterial species (Staphylococcus aureus, and Enterococcus faecalis), Gram-negative bacterial species (Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii), and fungi (Candida albicans). The covers remain effective even after undergoing multiple contamination cycles, after being cleaned, and when tinted to improve discretion and usability. Furthermore, as the release of iodine from the door handle covers follow hindered Fickian diffusion, their antimicrobial lifetime is calculated to be as long as approximately two years. Together, these results demonstrate the potential of these antimicrobial door handle covers to prevent cross-contamination, and underline the efficacy of integrating MOFs into innovative technologies., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Single tooth orange discoloration secondary to root canal calcification occurs as a consequence of dental trauma, orthodontic treatment, or for unknown rea- sons. A correct case history must be compiled and a CBCT study carried out in order to establish the diag- nosis and define the best treatment plan in each case. The aim of the present study was to offer a therapeutic protocol involving a clinical decision-making tree dia- gram based on the presence or absence of apical dis- ease and the degree of canal calcification. Dental bleaching and the use of ceramic veneers allow es- thetic restoration in such cases.

The very existence of a phase transition for spin glasses in an external magnetic field is controversial, even in high dimensions. We carry out massive simulations of the Ising spin-glass in a field, in six dimensions (which, according to classical-but not generally accepted-field-theoretical studies, is the upper critical dimension). We obtain results compatible with a second-order phase transition and estimate its critical exponents for the simulated lattice sizes. The detailed analysis performed by other authors of the replica symmetric Hamiltonian, under the hypothesis of critical behavior, predicts that the ratio of the renormalized coupling constants remain bounded as the correlation length grows. Our numerical results are in agreement with this expectation.

The precise arrangement and nature of atoms drive electronic phase transitions in condensed matter. To explore this tenuous link, we developed a true biaxial mechanical deformation device working at cryogenic temperatures, compatible with x-ray diffraction and transport measurements, well adapted to layered samples. Here we show that a slight deformation of TbTe 3 can have a dramatic influence on its Charge Density Wave (CDW), with an orientational transition from c to a driven by the a/c parameter, a tiny coexistence region near a = c, and without space group change. The CDW transition temperature T c displays a linear dependence with a / c - 1 while the gap saturates out of the coexistence region. This behaviour is well accounted for within a tight-binding model. Our results question the relationship between gap and T c in RTe 3 systems. This method opens a new route towards the study of coexisting or competing electronic orders in condensed matter., (© 2024. The Author(s).)

The apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide (APOBEC) family is composed of nucleic acid editors with roles ranging from antibody diversification to RNA editing. APOBEC2, a member of this family with an evolutionarily conserved nucleic acid-binding cytidine deaminase domain, has neither an established substrate nor function. Using a cellular model of muscle differentiation where APOBEC2 is inducibly expressed, we confirmed that APOBEC2 does not have the attributed molecular functions of the APOBEC family, such as RNA editing, DNA demethylation, and DNA mutation. Instead, we found that during muscle differentiation APOBEC2 occupied a specific motif within promoter regions; its removal from those regions resulted in transcriptional changes. Mechanistically, these changes reflect the direct interaction of APOBEC2 with histone deacetylase (HDAC) transcriptional corepressor complexes. We also found that APOBEC2 could bind DNA directly, in a sequence-specific fashion, suggesting that it functions as a recruiter of HDAC to specific genes whose promoters it occupies. These genes are normally suppressed during muscle cell differentiation, and their suppression may contribute to the safeguarding of muscle cell fate. Altogether, our results reveal a unique role for APOBEC2 within the APOBEC family., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Hyperglycaemia is an early and frequent adverse event during alpelisib treatment. METALLICA aimed to evaluate prophylactic metformin to prevent or reduce hyperglycaemia occurrence in patients with HR+/HER2-/ PIK3CA -mutated advanced breast cancer (ABC)., Methods: Between August 13th, 2020 and March 23rd, 2022, this 2-cohort, phase 2, multicentre, single-arm trial (NCT04300790) enrolled patients with HR+/HER2-/PIK3CA-mutated ABC: cohort A, normal glycaemia (fasting plasma glucose <100 mg/dL [<5.6 mmol/L] and HbA1c <5.7%), and cohort B, prediabetes (fasting plasma glucose 100-140 mg/dL [5.6-7.8 mmol/L] and/or haemoglobin A1C [HbA1c] 5.7-6.4%). Participants were at least 18 years old, with Eastern Cooperative Oncology Group performance status of 0-1, and up to two prior lines of endocrine therapy (ET) for ABC. Alpelisib plus ET were administered in 28-day cycles after initiation of prophylactic metformin plus ET. Primary endpoint was the incidence of grade 3-4 hyperglycaemia over the first 8 weeks. Secondary endpoints included safety, progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR). The primary objective for cohort A and B is met with ≤7 (14.6%) and ≤4 (20%) patients with grade 3-4 hyperglycaemia over the first 8 weeks, respectively., Findings: 233 patients were screened, and 68 (20.2%) patients were enrolled in cohorts A (n = 48) and B (n = 20). Median follow-up was 7.8 months (IQR 1.4-19.6). Over the first 8 weeks, one (2.1%) of 48 patients in cohort A (95% CI: 0.5-11.1; P  < 0.0001), and three (15.0%) of 20 patients in cohort B (95% CI: 5.6-37.8; P  = 0.016) had grade 3-4 hyperglycaemia. Serious treatment-related adverse events occurred in seven patients (10.3%). The most common were rash (two [2.9%]), vomiting (two [2.9%]), and diarrhoea (two [2.9%]). Discontinuation of alpelisib caused by AEs was reported in nine patients (13.2%), none caused by hyperglycaemia. At data cutoff (15 June, 2022), no treatment-related deaths were observed. In the full analysis set, median PFS was 7.3 months (95% CI: 5.9-not reached), ORR was 20.6% (95% CI: 11.7-32.1%), and CBR was 52.9% (95% CI: 40.4-65.2)., Interpretation: In HR+/HER2-/ PIK3CA -mutated ABC, prophylactic metformin before alpelisib plus endocrine treatment has low incidence and severity of alpelicib-induced hyperglycaemia., Funding: Novartis Pharmaceuticals., Competing Interests: ALC reports research support from Roche, Agendia, Lilly, Pfizer, Novartis, Merck Sharp & Dohme, Gilead, and Daichii-Sanyo; a consulting or advisory role with Lilly, Roche, Pfizer, and Novartis. Speakers’ bureaus for Lilly, AstraZeneca, Merck Sharp & Dohme; travel support from Roche, Pfizer, AstraZeneca; and stock or other ownership in MEDSIR and Initia-Research. JMPG reports a consulting or advisory role with Lilly, Roche, Eisai, Daichii Sankyo, AstraZeneca, Seattle Genetics; and employment at MEDSIR. MRB reports research support and participating in an advisory board of Novartis. PT reports a consulting or advisory role with AstraZeneca, Daiichi-Sankyo, Novartis and Seagen. Speakers’ bureaus for Pfizer, Novartis, Lilly, AstraZeneca, Daiichi-Sankyo and Seagen. IB reports grants and research support to the Institution: AstraZeneca, Lilly, Pfizer and Roche; honoraria and advisor colaboration: AstraZeneca, Roche, Novartis, Eisai, Celgene, Pfizer, Lilly, Pierre-Fabre, Bristol-Myers Squibb, Daiichi Sankyo, Grünenthal, Seagen and Veracyte and support for attending meetings and/or travel: AstraZeneca, Roche, Novartis, Pfizer, Lilly, Pierre-Fabre, Bristol-Myers Squibb and Daiichi Sankyo. BR reports travel support from Roche and Lilly. AFO reports travel support from Novartis. CS reports research support, consulting or advisory role from Genentech, AstraZeneca, Aragon Pharmaceuticals, Bayer Pharma, Byondis, Boehringer Ingelheim, Bristol-Myers Squibb, Cytomx Therapeutics, Daiichi Sankyo, F. Hoffmann-La Roche, Eisai, Genomic Health, GlaxoSmithKline, Innoup Farma, Eli Lilly, Macrogenics, Menarini Ricerche, Merck Sharp & Dohme, Merus, Millennium Pharmaceuticals, Novartis, Pfizer, Pierre Fabre, PintPharma, Puma Biotechnology, Sanofi, Seattle Genetics, Zymeworks. JPL reports honoraria from Seagen, Novartis, Pfizer, AstraZeneca/Daiichi Sankyo, Eli Lilly, Roche; and a consulting or advisory role with Seagen, Novartis, AstraZeneca/Daiichi Sankyo, Roche. EL reports honoraria from Ipsen, MSD, Pfizer, AstraZeneca/Daiichi Sankyo and Roche. EG reports honoraria from Roche/Genentech, Pfizer, Novartis, AstraZeneca, Seagen; a consulting or advisory role with AstraZeneca, Seagen, PharmaMar, Gilead Sciences; and speakers’ bureaus for Pfizer, Novartis, Roche. SGS reports honoraria for speaking from Novartis and GSK; Advisory role from Lilly, Seagen and Astra Zeneca; and travel expenses from Clovis and Pfizer outside the submitted work. EC reports consultancy and speakers’ bureaus for Novartis, Pfizer, Roche, Lilly, Celgene; and personal fees from Novartis, Pfizer, Roche, Lilly, Celgene, during the conduct of the study. JFC reports honoraria from Roche, AstraZeneca, Teva, Celgene, Pfizer, GSK, Novartis; and a consulting or advisory role with Roche, AstraZeneca, Pfizer, GSK, Novartis. MSC reports advisory Board of MEDSIR, Optimapharm; Speaker's Bureau in MEDSIR, Optimapharm; and Funding from MEDSIR, Optimapharm, FGP has taken part in advisory panels for Sanofi and Novo Nordisk; has received research support from Sanofi, Novo Nordisk, Boehringer Ingelheim Pharmaceuticals and Lilly; and has acted as a speaker for Sanofi, Novo Nordisk, Boehringer Ingelheim Pharmaceuticals, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Co. and Lilly. JC reports research support from ARIAD, Astrazeneca, Baxalta GMBH/Servier Affaires, Bayer, Eisai, Guardanth health, Merck Sharp & Dohme, Pfizer, Puma, Queen Mary University of London, Roche, Piqur; honoraria from Novartis, Eisai, Celgene, Pfizer, Roche, Samsung, Eli Lilly, Merck Sharp & Dohme Daiichi Sankyo; a consulting or advisory role with Celgene, Cellestia Biotech, AstraZeneca, Roche, Seattle Genetics, Daiichi Sankyo, ERYTECH Pharma, Polyphor, Athenex, Lilly, SERVIER, Merck Sharp & Dohme, GlaxoSmithKline, Leuko, Clovis Oncology, Bioasis, Boehringer Ingelheim, Ellipses Pharma, HiberCell, Bioinven, GEMoaB, Gilead Sciences, Menarini, Zymeworks, Reveal Genomics; stock or other ownership in Leuko, MEDSIR, Nektar; and travel support from Roche, Pfizer, Eisai, Novartis, Daiichi Sankyo. AU, EMD, SB, BB, MGC, PCC, AL, JLAR report no competing interests. JMPG, GM, PG, DAL, and MSC are employed by MEDSIR., (© 2024 Published by Elsevier Ltd.)

Preventing microbiological surface contamination in public spaces is nowadays of high priority. The proliferation of a microbial infection may arise through air, water, or direct contact with infected surfaces. Chemical sanitization is one of the most effective approaches to avoid the proliferation of microorganisms. However, extended contact with chemicals for cleaning purposes such as chlorine, hydrogen peroxide or ethanol may lead to long-term diseases as well as drowsiness or respiratory issues, not to mention environmental issues associated to their use. As a potentially safer alternative, in the present work, the efficacy and endurance of the antimicrobial activity of different sol-gel coatings were studied, where one or two biocides were added to the coating matrix resulting on active groups exposed on the surface. Specifically, the coating formulations were synthesized by the sol-gel method. Using the alkoxide route with acid catalysis a hybrid silica-titania-methacrylate matrix was obtained where aromatic liquid eugenol was added with a double function: as a complexing agent for the chelation of the reaction precursor titanium isopropoxide, and as a biocide. In addition, 2-Phenylphenol, ECHA approved biocide, has also been incorporated to the coating matrix. The antibacterial effect of these coatings was confirmed on Gram-positive ( Staphylococcus aureus ) and Gram-negative bacteria ( Escherichia coli ). Additionally, the coatings were non cyto-toxic and displayed virucidal activity. The coating chemical composition was characterized by 29 Si NMR, and ATR-FTIR. Furthermore, the thickness and the mechanical properties were characterized by profilometry and nanoindentation, respectively. Finally, the durability of the coatings was studied with tribology tests. Overall, our data support the efficacy of the tested sol-gel coatings and suggest that added features may be required to improve endurance of the antimicrobial effects on operational conditions ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Clinical care in modern intensive care units (ICUs) combines multidisciplinary expertise and a complex array of technologies. These technologies have clearly advanced the ability of clinicians to do more for patients, yet so much equipment also presents the possibility for cognitive overload., Purpose: The aim of this study was to investigate clinicians' experiences with and perceptions of technology in ICUs., Methodology/approach: We analyzed qualitative data from 30 interviews with ICU clinicians and frontline managers within four ICUs., Results: Our interviews identified three main challenges associated with technology in the ICU: (a) too many technologies and too much data; (b) inconsistent and inaccurate technologies; and (c) not enough integration among technologies, alignment with clinical workflows, and support for clinician identities. To address these challenges, interviewees highlighted mitigation strategies to address both social and technical systems and to achieve joint optimization., Conclusion: When new technologies are added to the ICU, they have potential both to improve and to disrupt patient care. To successfully implement technologies in the ICU, clinicians' perspectives are crucial. Understanding clinicians' perspectives can help limit the disruptive effects of new technologies, so clinicians can focus their time and attention on providing care to patients., Practice Implications: As technology and data continue to play an increasingly important role in ICU care, everyone involved in the design, development, approval, implementation, and use of technology should work together to apply a sociotechnical systems approach to reduce possible negative effects on clinical care for critically ill patients., Competing Interests: The authors are currently receiving a grant (Grant 2026498) from the National Science Foundation. Zhanna Novikov received a grant from the Israel Science Foundation (Grant No. 113/20). There are no other conflicts of interest or sources of funding for this research., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The effluents from conventional wastewater treatment plants (WWTP), even if accomplishing quality regulations, substantially differ in their characteristics with those of waters in natural environments. Constructed wetlands (CWs) serve as transitional ecosystems within WWTPs, mitigating these differences and restoring natural features before water is poured into the natural environment. Our study focused on an experimental surface-flow CW naturalizing the WWTP effluent in a semiarid area in Eastern Spain. Despite relatively low pollutant concentrations entering the CW, it effectively further reduced settled organic matter and nitrogen. Dissolved organic matter (DOM) reaching the CW was mainly protein-like, yet optical property changes in the DOM indicated increased humification, aromaticity, and stabilization as it flowed through the CW. Flow cytometry analysis revealed that the CW released less abundant but more active bacterial populations than those received. MiSeq Illumina sequencing highlighted changes in the prokaryotic community composition, with phyla Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria dominating the CW outflow. Functional prediction tools (FaproTax and PICRUSt2) demonstrated a shift towards microbial guilds aligned with those of the natural aquatic environments, increased aerobic chemoheterotrophs, photoautotrophs, and metabolic reactions at higher redox potentials. Enhanced capabilities for degrading plant material correlated well with changes in the DOM pool. Our findings emphasize the role of CWs in releasing biochemically stable DOM and functionally suited microbial populations for natural receiving environments. Consequently, we propose CWs as a naturalization nature-based solution (NBS) in water-scarce regions like the Mediterranean, where reclaimed discharged water can significantly contribute to ecosystem's water resources compared to natural flows., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Male adolescent sexual minorities are at elevated risk of HIV acquisition yet demonstrate low rates of PrEP uptake. Understanding the experiences of adolescents who have successfully accessed PrEP may inform ways to best support adolescents seeking PrEP. Adolescent sexual minorities ( N = 100) who reported utilizing PrEP responded to open-ended items asking about their initial PrEP experiences and advice for others. Qualitative analysis suggested that adolescents' ability to access PrEP is influenced by managing parental involvement and seeking culturally competent health care providers. Additionally, they reported how the benefits and drawbacks of taking PrEP played a role in their PrEP use. Findings suggest that educational PrEP interventions targeted at this population could improve uptake by incorporating discussions on side effects and mental health benefits associated with PrEP use. Structural interventions are warranted that improve adolescents' ability to seek sexual health care independently and make room for parental involvement when adolescents could benefit from their support.

Objectives: Mediterranean spotted fever is a common zoonosis in Europe caused by Rickettsia conorii bacterium . Among its wide range of clinical presentations, arterial thrombosis of large vessels has never been described before., Methods: We report a case of a complete acute infrarenal aortic thrombosis in a 61-year-old male with R. conorii infection ., Results and Conclusion: The patient was successfully operated using open aortic surgery and subsequent treatment with doxycycline. To our knowledge, this is the first report of aortic thrombosis associated with infection by this parasite, extending the clinical spectrum of the disease., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The primary objective of this study was to explore the acceptability of task shifting to volunteer barangay health workers (BHWs) in the implementation of community-based Diabetes Self-Management Education (DSME) in the Philippines., Methods: This study employed a descriptive qualitative study design. Data were collected through semi-structured interviews with twelve stakeholders. The study was conducted in the urban city of Marikina which has a high prevalence of diabetes, and high death rates for diabetes and cerebrovascular disease relative to the regional and national rates. A purposive sampling technique was used in selecting participants., Results: Task shifting Diabetes Self-Management Education to BHWs is generally acceptable to the participants. Expanding the roles of BHWs should be supported by adequate training, compensation, supervision, and financial and non-financial incentives. Ensuring adequate support and resources to execute BHWs' duties and responsibilities as volunteer health workers can promote the effective implementation of task shifting DSME in primary care., Conclusion: Findings from this study provide preliminary evidence of the acceptability of task shifting to BHWs in the management of diabetes mellitus. The study highlights the importance of institutionalizing task shifting in the health system to promote acceptance and sustainability., Competing Interests: Both authors declared no conflicts of interest., (© 2023 Acta Medica Philippina.)

During the pandemic, assisted reproductive treatments suffered from major disruptions in their terms due to the restrictions imposed. The objective of this study is to evaluate the level of anxiety of women whose treatments were either suspended or delayed., Methods: Descriptive cross-sectional study conducted between April and May 2020. The State-Trait Anxiety Inventory was applied by telephone in a Spanish adapted version. The research also included social, personal, and work aspects which may be involved in the challenging situation., Results: A total of 115 patients participated in the study (73.7%). Women showed a mean in trait anxiety of 17.79 (SD = 8.80) and a mean in state anxiety of 19.95 (SD = 9.08). Neither the type of treatment nor the time of infertility were predictors of trait anxiety or state anxiety. Greater age pressure and more worry were associated to greater trait and state anxiety ( p < 0.001). The most common emotional reactions to discontinuation of fertility treatments were sadness and anxiety., Conclusions: Discontinuation of fertility treatments due to confinement restrictions had a negative impact on the mental health of women who were following a process of assisted reproduction treatment, increasing their levels of emotional distress and anxiety.

Background: Cryopreservation currently represents the most suitable strategy for the long-term conservation of plant germplasm. While much effort has focused on the development of protocols to enable successful cryostorage, there are few, if any reports, that consider the effect of cryogenic temperatures on the phytohormone status of the seed and developing seedlings., Objective: To investigate the effect of cryopreservation on external seed coat features as well as levels of indole-3-acetic acid (IAA), abscisic acid (ABA) and 1-aminocyclopropane-1-carboxylic acid (ACC) in maize., Materials and Methods: Two groups of seeds at 6% moisture content were compared: one was maintained at 4 degree C (control) while the other was exposed to LN within cryo-vials., Results: Seeds exposed to cryogenic temperatures were characterized by the presence of large cracks in the seed coat compared with control seeds. Cryogenic exposure also resulted in a reduction in biomass and plant height. Results from the phytohormone analysis showed an initial reduction in the levels of IAA, ABA and ACC after 7 days of growth followed by sharp increase in levels relative to the control by 14 days. Whilst the roles of ABA and ethylene (and by extension, its precursor ACC) are well studied as stress response molecules, much less is known about the potentially vital role of auxins in regulating plant growth under conditions of low temperature stress., Conclusion: It is postulated that the interaction of all three hormones modulate crosstalk between various stress responses and recovery pathways to ameliorate the damage caused by freezing stress and enable plant survival. Given the dearth of information on phytohormones in cryobiology, more studies are needed to fully elucidate these relationships in the context of freezing stress caused by liquid nitrogen. Doi.org/10.54680/fr23610110612.

The Bísaro pig is a Portuguese autochthonous breed greatly appreciated for its meat quality and is mainly reared outdoors. Immunocastration could be a solution to avoid undesirable pregnancies and boar taint in cull sows. The present study tested three immunocastration protocols (with Improvac ® ) according to their reproductive cycle. The first inoculation was performed two weeks after farrowing (IM1, n = 5), at the beginning of estrus (IM2, n = 5), and one week after the end of estrus (IM3, n = 5), followed by a second administration four weeks apart. A control group (C, n = 5) was also included in the same housing conditions. The sample collection included the reproductive tract for morphometric evaluation, neck fat for the quantification of boar taint compounds, and a portion of the Longissimus thoracis et lumborum for meat quality trait assessment. The reproductive tracts from intact sows (C) were significantly heavier compared to the immunocastrated groups ( p < 0.05) (1.403 kg C to 0.508 kg IM1, 0.590 kg IM2, and 0.599 kg IM3), suggesting the regression of the reproductive tract to nonstimulated conditions due to immunization against GnRH. The IM1 group exhibited significantly smaller reproductive tract measurements compared to group C for most of the evaluated segments ( p < 0.05). No marked differences were observed in the meat quality traits. Therefore, immunocastration can be used in culling sows to avoid ovarian activity, and it is not detrimental to pork quality traits.

We study the interface representation of the contact process at its directed-percolation critical point, where the scaling properties of the interface can be related to those of the original particle model. Interestingly, such a behavior happens to be intrinsically anomalous and more complex than that described by the standard Family-Vicsek dynamic scaling Ansatz of surface kinetic roughening. We expand on a previous numerical study by Dickman and Muñoz [Phys. Rev. E 62, 7632 (2000)10.1103/PhysRevE.62.7632] to fully characterize the kinetic roughening universality class for interface dimensions d=1,2, and 3. Beyond obtaining scaling exponent values, we characterize the interface fluctuations via their probability density function (PDF) and covariance, seen to display universal properties which are qualitatively similar to those recently assessed for the Kardar-Parisi-Zhang (KPZ) and other important universality classes of kinetic roughening. Quantitatively, while for d=1 the interface covariance seems to be well described by the KPZ, Airy&#95;{1} covariance, no such agreement occurs in terms of the fluctuation PDF or the scaling exponents.

Subtilisin-like enzymes are recognized as key players in many infectious agents. In this context, its inhibitors are very valuable molecular lead compounds for structure based drug discovery and design. Marine invertebrates offer a great source of bioactive molecules, including protease inhibitors. In this work, we describe a new subtilisin inhibitor, from the sea anemone Condylactis gigantea (CogiTx1). CogiTx1 was purified using a combination of cation exchange chromatography, size exclusion chromatography and RP-HPLC chromatography. CogiTx1 it is a protein with 46 amino acid residues, with 4970.44 Da and three disulfide bridges. Is also able to inhibit subtilisin-like enzymes and pancreatic elastase. According to the amino acid sequence, it belongs to the defensin 4 family of proteins. The sequencing showed that CogiTx1 has an amidated C-terminal end, which was confirmed by the presence of the typical -XGR signal for amidation in the protein sequence deduced from the cDNA. This modification was described at protein level for the first time in this family of proteins. CogiTx1 is the first subtilisin inhibitor from the defensin 4 family and accordingly it has a folding consisting primarily in beta-strands in agreement with the analysis by CD and 3D modelling. Therefore, future in-depth functional studies may allow a more detailed characterization and will shed light on structure-function properties., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Background: N. wightii (Leguminosae) is valued as a cover crop and as a potential source of protein in food insecure countries. However, plantlet establishment is limited by physical dormancy. Our previous work has shown that exposure of N. wightii seeds to cryogenic temperatures is able to overcome physical dormancy., Objective: The current study is an extension of that work where the field performance and nutritional composition of plants regenerated from N. wightii seeds was investigated., Results: It was evident that plants regenerated from cryopreserved seeds displayed faster growth rates than those from control seeds. In addition, cryopreservation did not alter the nutritional profile of plants produced from cryo-stored seeds., Conclusion: Collectively, the results indicate that cryopreservation serves as a suitable strategy for the preservation of seeds of N. wightii with the added benefit of also serving as a dormancy breaking mechanism upon retrieval from cryogenic temperatures. Doi.org/10.54680/fr23510110712.

Aging is characterized by a gradual decline in physiological function. This process affects all organs including the adrenal cortex, which normally functions to produce essential steroid hormones including mineralocorticoids, glucocorticoids, and androgens. With increasing age, features such as reduced adrenal cortex size, altered zonation, and increased myeloid immune cell infiltration substantially alter the structure and function of the adrenal cortex. Many of these hallmark features of adrenal cortex aging occur both in males and females, yet are more enhanced in males. Hormonally, a substantial reduction in adrenal androgens is a key feature of aging, which is accompanied by modest changes in aldosterone and cortisol. These hormonal changes are associated with various pathological consequences including impaired immune responses, decreased bone health, and accelerated age-related diseases. One of the most notable changes with adrenal aging is the increased incidence of adrenal tumors, which is sex dimorphic with a higher prevalence in females. Increased adrenal tumorigenesis with age is likely driven by both an increase in genetic mutations as well as remodeling of the tissue microenvironment. Novel antiaging strategies offer a promising avenue to mitigate adrenal aging and alleviate age-associated pathologies, including adrenal tumors., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Despite the evidence of elevated autistic behaviors and co-occurring neurodevelopmental difficulties in many children with neurofibromatosis type 1 (NF1), we have a limited understanding of the sensory processing challenges that may occur with the condition. This study examined the sensory profile of children and adolescents with NF1 and investigated the relationships between the sensory profiles and patient characteristics and neuropsychological functioning. The parent/caregivers of 152 children with NF1 and 96 typically developing children completed the Sensory Profile 2 (SP2), along with standardized questionnaires assessing autistic behaviors, ADHD symptoms, internalizing symptoms, adaptive functioning, and social skills. Intellectual functioning was also assessed. The SP2 data indicated elevated sensory processing problems in children with NF1 compared to typically developing children. Over 40% of children with NF1 displayed differences in sensory registration (missing sensory input) and were unusually sensitive to and unusually avoidant of sensory stimuli. Sixty percent of children with NF1 displayed difficulties in one or more sensory modalities. Elevated autistic behaviors and ADHD symptoms were associated with more severe sensory processing difficulties. This first detailed assessment of sensory processing, alongside other clinical features, in a relatively large cohort of children and adolescents with NF1 demonstrates the relationships between sensory processing differences and adaptive skills and behavior, as well as psychological well-being. Our characterization of the sensory profile within a genetic syndrome may help facilitate more targeted interventions to support overall functioning.

This clinical report describes a multidisciplinary protocol for the management of a severely discolored nonvital maxillary anterior tooth based on minimally invasive treatment with in-office and home bleaching combined with restoration with composite resin., (Copyright © 2023 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Aging markedly increases cancer risk, yet our mechanistic understanding of how aging influences cancer initiation is limited. Here we demonstrate that the loss of ZNRF3, an inhibitor of Wnt signaling that is frequently mutated in adrenocortical carcinoma, leads to the induction of cellular senescence that remodels the tissue microenvironment and ultimately permits metastatic adrenal cancer in old animals. The effects are sexually dimorphic, with males exhibiting earlier senescence activation and a greater innate immune response, driven in part by androgens, resulting in high myeloid cell accumulation and lower incidence of malignancy. Conversely, females present a dampened immune response and increased susceptibility to metastatic cancer. Senescence-recruited myeloid cells become depleted as tumors progress, which is recapitulated in patients in whom a low myeloid signature is associated with worse outcomes. Our study uncovers a role for myeloid cells in restraining adrenal cancer with substantial prognostic value and provides a model for interrogating pleiotropic effects of cellular senescence in cancer., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Ultrasound processing has been widely applied in food sector for various applications such as decontamination and structural and functional components modifications in food. Enzymes are proteinaceous in nature and are widely used due to its catalytic activity. To mitigate the undesirable effects caused by the enzymes various technologies have been utilized to inactive the enzymes and improve the enzyme efficiency. Ultrasound is an emerging technology that produces acoustic waves which causes rapid formation and collapse of bubbles. It has the capacity to break the hydrogen bonds and interact with the polypeptide chains due to Vander Waals forces leading to the alteration of the secondary and tertiary structure of the enzymes thereby leading to loss in their biological activity. US effectively inactivates various dairy-related enzymes, including alkaline phosphatase (ALP), lactoperoxidase (LPO), and γ-glutamyl transpeptidase (GGTP) with increased US intensity and time without affecting the natural dairy flavors. The review also demonstrates that inactivation of enzymes presents in fruit and vegetables such as polyphenol oxidase (PPO), polygalacturonase (PG), Pectin methyl esterase (PME), and peroxidase. The presence of the enzymes causes detrimental effects causes off-flavors, off-colors, cloudiness, reduction in viscosity of juices, therefore the formation of high-energy free molecules during sonication affects the catalytic function of enzymes and thereby causing inactivation. Therefore this manuscript elucidates the recent advances made in the inactivation of common, enzymes infruits, vegetables and dairy products by the application of ultrasound and also explains the enzyme inactivation kinetics associated. Further this manuscript also discusses the ultrasound with other combined technologies, mechanisms, and its effects on the enzyme inactivation., 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.)

The need for convenient tools to express transgenes over a large dynamic range is pervasive throughout plant synthetic biology; however, current efforts are largely limited by the heavy reliance on a small set of strong promoters, precluding more nuanced and refined engineering endeavors in planta . To address this technical gap, we characterize a suite of constitutive promoters that span a wide range of transcriptional levels and develop a GoldenGate-based plasmid toolkit named PCONS, optimized for versatile cloning and rapid testing of transgene expression at varying strengths. We demonstrate how easy access to a stepwise gradient of expression levels can be used for optimizing synthetic transcriptional systems and the production of small molecules in planta . We also systematically investigate the potential of using PCONS as an internal standard in plant biology experimental design, establishing the best practices for signal normalization in experiments. Although our library has primarily been developed for optimizing expression in N. benthamiana , we demonstrate the translatability of our promoters across distantly related species using a multiplexed reporter assay with barcoded transcripts. Our findings showcase the advantages of the PCONS library as an invaluable toolkit for plant synthetic biology.

Current therapies for treating Glioblastoma (GB), and brain tumours in general, are inefficient and represent numerous challenges. In addition to surgical resection, chemotherapy and radiotherapy are presently used as standards of care. However, treated patients still face a dismal prognosis with a median survival below 15-18 months. Temozolomide (TMZ) is the main chemotherapeutic agent administered; however, intrinsic or acquired resistance to TMZ contributes to the limited efficacy of this drug. To circumvent the current drawbacks in GB treatment, a large number of classical and non-classical platinum complexes have been prepared and tested for anticancer activity, especially platinum (IV)-based prodrugs. Platinum complexes, used as alkylating agents in the anticancer chemotherapy of some malignancies, are though often associated with severe systemic toxicity (i.e., neurotoxicity), especially after long-term treatments. The objective of the current developments is to produce novel nanoformulations with improved lipophilicity and passive diffusion, promoting intracellular accumulation, while reducing toxicity and optimizing the concomitant treatment of chemo-/radiotherapy. Moreover, the blood-brain barrier (BBB) prevents the access of the drugs to the brain and accumulation in tumour cells, so it represents a key challenge for GB management. The development of novel nanomedicines with the ability to (i) encapsulate Pt-based drugs and pro-drugs, (ii) cross the BBB, and (iii) specifically target cancer cells represents a promising approach to increase the therapeutic effect of the anticancer drugs and reduce undesired side effects. In this review, a critical discussion is presented concerning different families of nanoparticles able to encapsulate platinum anticancer drugs and their application for GB treatment, emphasizing their potential for increasing the effectiveness of platinum-based drugs.

Background: COVID-19 patients with any pre-existing major cardio-vascular disease (CVD) are at the highest risk of viral infection and of developing severe disease. The pathophysiological mechanism is characterized by the viral link to angiotensin-converting enzyme 2 (ACE2) and the involvement of the endothelial system with the release of cytokines and the inflicting of direct damage to the myocardium, the induction of microthrombosis, and the initiation of alterations in oxygen diffusion. The aim of the study is to analyze the clinical course and outcomes in patients (gender-stratified) with pre-existing major CVD., Methods: Out of the 1833 (973 M/860 F) patients admitted to the Internal Medicine COVID-19 Unit of "Castelli Hospital", Lazio, Italy, from 1 January 2021 to 31 December 2021, 600 patients (320 M/280 F) with a mean age of 77 (78.6 M/75.1 F) previously had CVD. Demographic characteristics, length of the stay (LOS) and oxygen therapy were evaluated., Results: All of the CVD COVID-19 patients underwent non-invasive ventilation (NIV). CVD was linked with increased LOS (21 days F/22 M) compared to no CVD (19 days). In total, 32.7% of total patients had major CVD., Conclusions: Timely identification and evaluation of patients with pre-existing major CVD are fundamental for adequate treatment based on gender, severity, state of illness and for risk reduction.

Background: Immunoglobulin E (IgE)-mediated food allergies (FAs) are increasingly common among US children and adults. Not only can living with FA impose considerable physical health impacts, but it also imposes economic burden and can negatively affect quality of life. Limited data indicate that allergy to multiple foods (multi-FA) also may be common, but much remains unknown about its distribution and determinants., Objective: To characterize the prevalence, characteristics, determinants, psychosocial burden, and distribution of multi-FA among a large, nationally representative sample of US children and adults., Methods: A US population-based survey was administered. Estimates of multi-FA prevalence, conditional frequencies of multi-FA combinations, and associated factors were derived. Latent class analyses were conducted using 9 dichotomized indicators of specific FA prevalence, which were used to determine factors associated with latent class membership and characterize FA-related psychosocial burden within each class., Results: Surveys were completed for 38,408 children and 40,443 adults. Among children and adults meeting established symptom-report criteria for FA, an estimated 40% and 48% had multi-FA, respectively. Among pediatric and adult populations with convincing FAs, the lifetime reported prevalence of physician-diagnosed atopic comorbidities increased significantly as the number of reported current convincing FAs increased, as did the proportion reporting multi-FA-related health care utilization and higher perceived psychosocial burden. Latent class analyses suggested the existence of the following 4 key latent phenotypes of multi-FA: milk and egg-dominant, seafood-dominant, peanut and tree nut-dominant, and broadly multi-food allergic., Conclusion: The US population-level burden of multi-FA is high among both children and adults, and data indicate the presence of 4 major phenotypes of multi-FA in both populations., (Copyright © 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)