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Cannabidiol (CBD) is garnering increasing interest due to its significant biological activity. This natural compound is one of the major cannabinoids in Cannabis sativa L. In this work, we describe the encapsulation of CBD in solid and hollow pH-sensitive poly(4-vinylpyridine) (solid@p4VP and hollow@p4VP) nanoparticles, and temperature-sensitive poly(N-isopropylacrylamide) (solid@pNIPAM and hollow@pNIPAM) nanoparticles for transport and release CBD in a controlled manner. The CBD loading into these smart polymeric systems was effective and their release profiles, solubility and resistance to stomach and intestinal conditions were evaluated, showing satisfactory properties and improved bioavailability with respect to free CBD. Finally, the A549 human lung cancer cell line was used as lung adenocarcinoma epithelial cellular model to carry out preliminary assays of the in vitro activity of the vehiculized CBD. For all these studies, synthetic CBD was employed, for which a new efficient and scalable synthesis of cannabinoids has been developed., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

The Quest for Orthologs (QfO) orthology benchmark service (https://orthology.benchmarkservice.org) hosts a wide range of standardized benchmarks for orthology inference evaluation. It is supported and maintained by the QfO consortium, and is used to gather ortholog predictions and to examine strengths and weaknesses of newly developed and existing orthology inference methods. The web server allows different inference methods to be compared in a standardized way using the same proteome data. The benchmark results are useful for developing new methods and can help researchers to guide their choice of orthology method for applications in comparative genomics and phylogenetic analysis. We here present a new release of the Orthology Benchmark Service with a new benchmark based on feature architecture similarity as well as updated reference proteomes. We further provide a meta-analysis of the public predictions from 18 different orthology assignment methods to reveal how they relate in terms of ortholog predictions and benchmark performance. These results can guide users of orthologs to the best suited method for their purpose., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

Leadership positions with enormous responsibilities are challenging; at times leaders may feel isolated or lonely. A mastermind team is a small group of peer-mentors or a personal board of directors, who meet on a recurring basis to share ideas for feedback, groupsource solutions, and to celebrate/commiserate on events. Joining a mastermind team helps leaders receive psychological support, encouragement, inspiration, suggestions for solving problems, and resources to manage challenges. This commentary reviews the purpose and concept of mastermind teams. Included in the review are practical suggestions for ways to form a team, set ground rules, implement engagement approaches, establish meeting formats, and create psychological safety. Mastermind teams can help leaders grow personally and professionally., Competing Interests: Conflict of Interest The authors have no conflicts of interest., (Copyright © 2024 American Association of Colleges of Pharmacy. Published by Elsevier Inc. All rights reserved.)

In this manuscript, we draw on the insights from Kahneman, Sibony, and Sunsteins influential nonfiction book Noise: A Flaw in Human Judgment to explore the concept of unwanted variability in judgment (i.e., noise). We introduce key terms and connect these insights to the field of radiation oncology by illustrating how noise contributes to errors in clinically relevant areas such as contouring. Additionally, we propose practical strategies to reduce noise in radiation oncology, such as through judgment aggregation and the use of artificial intelligence tools, building on the principles outlined in the book.

Plant-plant interactions are important drivers for the functioning and structuring of dryland plant communities. Stressful conditions, mainly related to water availability, determine whether plant interactions result in net facilitation or competition. Many studies have been conducted on the impacts of mature individuals, trees, shrubs or tussock grasses, on woody seedlings but little is known about the biotic interactions when they all are at the same developmental stage under field conditions. Here we present a spatially replicated study with Olea europaea as the target species and Pistacia lentiscus and Macrochloa tenacissima as neigbors. We also implemented field techniques to increase water availability and, hence, reproduce an abiotic gradient of stress. Wild olive performance was sensitive to neighbors, water availability and site. Improved microcatchments, which in addition to site recreated a gradient of water availability, improved wild olive performance as well as planted neighbors negatively impacted olive seedlings. We observed increasing negative interacting effects as conditions become less stressful. This is in line with the stress-gradient-hypothesis but also provides important knowledge regarding plant interactions in drylands at the same development stage., 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 B.V. All rights reserved.)

Background/purpose: The use of artificial intelligence (AI) in radiotherapy (RT) is expanding rapidly. However, there exists a notable lack of clinician trust in AI models, underscoring the need for effective uncertainty quantification (UQ) methods. The purpose of this study was to scope existing literature related to UQ in RT, identify areas of improvement, and determine future directions., Methods: We followed the PRISMA-ScR scoping review reporting guidelines. We utilized the population (human cancer patients), concept (utilization of AI UQ), context (radiotherapy applications) framework to structure our search and screening process. We conducted a systematic search spanning seven databases, supplemented by manual curation, up to January 2024. Our search yielded a total of 8980 articles for initial review. Manuscript screening and data extraction was performed in Covidence. Data extraction categories included general study characteristics, RT characteristics, AI characteristics, and UQ characteristics., Results: We identified 56 articles published from 2015 to 2024. 10 domains of RT applications were represented; most studies evaluated auto-contouring (50 %), followed by image-synthesis (13 %), and multiple applications simultaneously (11 %). 12 disease sites were represented, with head and neck cancer being the most common disease site independent of application space (32 %). Imaging data was used in 91 % of studies, while only 13 % incorporated RT dose information. Most studies focused on failure detection as the main application of UQ (60 %), with Monte Carlo dropout being the most commonly implemented UQ method (32 %) followed by ensembling (16 %). 55 % of studies did not share code or datasets., Conclusion: Our review revealed a lack of diversity in UQ for RT applications beyond auto-contouring. Moreover, we identified a clear need to study additional UQ methods, such as conformal prediction. Our results may incentivize the development of guidelines for reporting and implementation of UQ in RT., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [KAW serves as an Editorial Board Member for Physics and Imaging in Radiation Oncology. CDF has received travel, speaker honoraria and/or registration fee waiver unrelated to this project from: The American Association for Physicists in Medicine; the University of Alabama-Birmingham; The American Society for Clinical Oncology; The Royal Australian and New Zealand College of Radiologists; The American Society for Radiation Oncology; The Radiological Society of North America; and The European Society for Radiation Oncology]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Diagnosis of neurological involvement in Lyme disease is based on two-step serological testing and cerebrospinal fluid pleocytosis. In Spain its incidence is much lower than in other European countries, being Asturias the region with the highest incidence. We tried to analyse the clinical and epidemiological aspects in the main hospital in Asturias., Material Y Methods: Retrospective observational study of patients admitted for Lyme disease in our center over 14years (2009-2022). Clinical, analytical and evolutionary variables were analyzed after one year. Active neuroborreliosis was diagnosed after registering pleocytosis and positive serologies at the cerebrospinal fluid., Results: 108 episodes were analyzed, corresponding to 100 patients coded at discharge as Lyme disease. 58 episodes are discarded due to diagnostic or coding error. 51 episodes were considered active disease, being 38 diagnosed of neuroborreliosis. Tick bite recall and erythema were reported in 55.3% and 31.6% of patients. The most frequent neurological syndromes were radiculoneuritis (36.84%), bilateral facial palsy (13.56%), radiculoneuritis and bilateral facial palsy (10.52%) and multiple cranial mononeuropathy (10.52%), among others. 78.9% achieved a complete recovery, and 15.79% developed post-treatment Lyme disease syndrome., Discussion: Despite the high incidence of Lyme disease in Asturias, the cases based on hospital admission that can be classified as active disease are lower than those published based on hospital coding. The main source of diagnostic error is positive serological results, without other clinical context, especially in patients studied for cognitive impairment or encephalopathy., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

The growth rate of in situ-induced hepatic lesions in an Oncopig large animal model is quantitatively assessed. Oncopigs (n = 9) received baseline triple-phase CT scans prior to lesion induction. Lesions were subsequently induced by delivering the Ad-Cre vector to four locations in the liver. Triple-phase CT scans were obtained weekly to track the growth of the lesions. Animals were sacrificed at 14, 21, or 28 days (n = 3 in each group). The overall success rate of lesion generation was ~78%. Histopathology sections consistently revealed lesions that were highly inflammatory and consisted of a large leukocyte population without clear evidence of carcinomas. Lesions presented within imaging as hypovascular, low attenuating masses with slight contrast enhancement around the margins but little to no enhancement within the lesions themselves. The observed lesions were manually segmented on the venous phase image. Segmentation volumes were fitted to a logistic growth and decay model. Several lesions observed at earlier time points in the 28-day group had fully regressed by the time of the necropsy. The overall trend of rapid growth for the first 21 days, with spontaneous regression of the lesions being observed from day 21 to 28, suggests that the optimal window for experimental studies may be from days 14 to 21. The data and mathematical models generated from this study may be used for future computational models; however, the current model presented has moderate clinical relevance because many induced tumors resolved spontaneously within a few weeks. Awareness and careful consideration of the modest relevance and limitations of the model are advisable for each specific use case.

The era of biodiversity genomics is characterized by large-scale genome sequencing efforts that aim to represent each living taxon with an assembled genome. Generating knowledge from this wealth of data has not kept up with this pace. We here discuss major challenges to integrating these novel genomes into a comprehensive functional and evolutionary network spanning the tree of life. In summary, the expanding datasets create a need for scalable gene annotation methods. To trace gene function across species, new methods must seek to increase the resolution of ortholog analyses, e.g. by extending analyses to the protein domain level and by accounting for alternative splicing. Additionally, the scope of orthology prediction should be pushed beyond well-investigated proteomes. This demands the development of specialized methods for the identification of orthologs to short proteins and noncoding RNAs and for the functional characterization of novel gene families. Furthermore, protein structures predicted by machine learning are now readily available, but this new information is yet to be integrated with orthology-based analyses. Finally, an increasing focus should be placed on making orthology assignments adhere to the findable, accessible, interoperable, and reusable (FAIR) principles. This fosters green bioinformatics by avoiding redundant computations and helps integrating diverse scientific communities sharing the need for comparative genetics and genomics information. It should also help with communicating orthology-related concepts in a format that is accessible to the public, to counteract existing misinformation about evolution., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

The overuse of antimicrobials in livestock has contributed to the emergence and selection of clinically relevant multidrug-resistant bacteria. In Brazil, there is no conclusive information on the occurrence of Escherichia coli producing extended-spectrum β-lactamase (ESβL) in cattle breeding, which is an important sector of agribusiness in this country. Herein, we investigated the presence of ESβL-positive E. coli strains in dairy cattle from a commercial farm with routine practice of therapeutic cephalosporins. Ninety-five rectal swab samples were collected from healthy dairy calves and cows under treatment with ceftiofur. Samples were screened for the presence of ESβL producers, and positive isolates were identified by MALDI-TOF, with subsequent screening for genes encoding ESβL variants by PCR and sequencing. The presence of ESβL (CTX-M-15)-producing E. coli was confirmed in calves, and lactating and dry cows. Most ESβL strains with genetic homologies ≥ 90% were grouped into two major PFGE clusters, confirming the suscessful expansion of clonally related lineages in animals from different lactating cycles, on the same property. Four representatives CTX-M-15-positive E. coli strains had their genomes sequenced, belonging to the clonal complex (CC) 23 and sequence type (ST) 90. A phylogeographical landscape of ST90 was performed revealing a global One Health linkage. Our results highlight the intestinal microbiota of dairy cattle as a hotspot for the spread of critical priority ESβL-producing E. coli and demonstrate that ST90 is an international clone genomically adapted to human and animal hosts, which deserve additional investigation to determine its zoonotic potential and impact in food chain., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background/Objectives : Magnetic Fe 3 O 4 nanoparticles (MNPs) are becoming more important every day. We prepared MNPs in a simple one-step reaction by following the solvothermal method, assisted by azide and alkyne functionalized polyethylene glycol (PEG400) polymers, as well as by PEG6000 and the polyol β-cyclodextrin (βCD), which played a crucial role as electrostatic stabilizers, providing polymeric/polyol coatings around the magnetic cores. Methods : The composition, morphology, and magnetic properties of the nanospheres were analyzed using Transmission Electron and Atomic Force Microscopies (TEM, AFM), Nuclear Magnetic Resonance (NMR), X-ray Diffraction Diffractometry (XRD), Fourier-Transform Infrared Spectroscopy (FT-IR), Matrix-Assisted Laser Desorption/Ionization (MALDI) and Vibrating Sample Magnetometry (VSM). Results : The obtained nanoparticles (@Fe 3 O 4 -PEGs and @Fe 3 O 4 -βCD) showed diameters between 90 and 250 nm, depending on the polymer used and the Fe 3 O 4 ·6H 2 O precursor concentration, typically, 0.13 M at 200 °C and 24 h of reaction. MNPs exhibited superparamagnetism with high saturation mass magnetization at room temperature, reaching values of 59.9 emu/g (@Fe 3 O 4 -PEG6000), and no ferromagnetism. Likewise, they showed temperature elevation after applying an alternating magnetic field (AMF), obtaining Specific Absorption Rate (SAR) values of up to 51.87 ± 2.23 W/g for @Fe 3 O 4 -PEG6000. Additionally, the formed systems are susceptible to click chemistry, as was demonstrated in the case of the cannabidiol-propargyl derivative (CBD-Pro), which was synthesized and covalently attached to the azide functionalized surface of @Fe 3 O 4 -PEG400-N 3 . Prepared MNPs are highly dispersible in water, PBS, and citrate buffer, remaining in suspension for over 2 weeks, and non-toxic in the T84 human colon cancer cell line, Conclusions : indicating that they are ideal candidates for biomedical applications.

Objective: Innovative therapies such as thermoembolization are expected to play an important role in improving care for patients with diseases such as hepatocellular carcinoma. Thermoembolization is a minimally invasive strategy that combines thermal ablation and embolization in a single procedure. This approach exploits an exothermic chemical reaction that occurs when an acid chloride is delivered via an endovascular route. However, comprehension of the complexities of the biophysics of thermoembolization is challenging. Mathematical models can aid in understanding such complex processes and assisting clinicians in making informed decisions. In this study, we used a Hagen-Poiseuille 1D blood flow model to predict the mass transport and possible embolization locations in a porcine hepatic artery., Method: The 1D flow model was used on imaging data of in-vivo embolization imaging data of three pigs. The hydrolysis time constant of acid chloride chemical reaction was optimized for each pig, and LOOCV method was used to test the model's predictive ability., Conclusion: This basic model provided a balanced accuracy rate of 66.8% for identifying the possible locations of damage in the hepatic artery. Use of the model provides an initial understanding of the vascular transport phenomena that are predicted to occur as a result of thermoembolization.

Referencing literature and professional experiences of multiple academic affairs deans in Doctor of Pharmacy degree granting programs, this commentary examines the ways offices of academic affairs (OAAs) play an integral part in the professional identity formation (PIF) of students, faculty, preceptors, and staff. The overlapping roles of academic affairs and other program and university offices are examined with a focus on approaches that impact student PIF. Although size, organizational structure, and roles or responsibilities can vary among OAAs within pharmacy education, 5 focus areas are identified as opportunities where most, if not all, OAAs can positively impact PIF for students. These 5 areas include curriculum design, delivery, and operations; leadership; professional development; student support and progression; and accreditation. OAAs can help to shape PIF within pharmacy education in a variety of ways. Identifying and reflecting upon the 5 focus areas described in this paper may help individuals within OAA units to recognize where PIF efforts may be developed, refined, or assessed within their program. By intentionally layering PIF strategies across these 5 focus areas, OAA personnel and those from other units within and outside of the university system may thoughtfully work together to develop graduates who have increased self-awareness, confidence, and the ability to lead within the profession of pharmacy., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2024 American Association of Colleges of Pharmacy. Published by Elsevier Inc. All rights reserved.)

Plants provide a wide array of compounds that can be explored for potential anticancer properties. Siphonochilone, a furanoterpene that represents one of the main components of the African plant Siphonochilus aethiopicus, shows numerous health benefits. However, to date, its antiproliferative properties have not been tested. The aim of this study was to analyze the cytotoxic effects of siphonochilone on a panel of cancer cell lines and its underlying mechanism of action. Our results demonstrated that siphonochilone exhibited significant cytotoxic effects on pancreatic, breast, lung, colon, and liver cancer cell lines showing a IC 50 ranging from 22 to 124 μM at 72 h of treatment and highlighting its cytotoxic effect against MCF7 and PANC1 breast and pancreas cancer cell lines (22.03 and 39.03 μM, respectively). Cell death in these tumor lines was mediated by apoptosis by the mitochondrial pathway, as evidenced by siphonochilone-induced depolarization of the mitochondrial membrane potential. In addition, siphonochilone treatment involves the generation of reactive oxygen species that may contribute to apoptosis induction. In this work, we described for the first time the cytotoxic properties of siphonochilone and provided data about the molecular processes of cell death. Although future studies will be necessary, our results support the interest in this molecule in relation to their clinical application in cancer, and especially in breast and pancreatic cancer., (© 2024 The Authors. Environmental Toxicology published by Wiley Periodicals LLC.)

The present study aims to explore and compare psychosocial risks and work overload among nursing professionals in the field mental health and psychiatry in Chile. Quantitative, observational and cross-sectional research was designed for this purpose. Nurses from community, ambulatory, hospital and emergency units in mental health and psychiatry in Chile were recruited between January and May 2022. Instruments of psychosocial variables and an occupational psychosocial risk scale based on the Copenhagen Psychosocial Questionnaire were used. Descriptive and correlational statistics were used, as well as independent samples t-tests, Factorial Anova and post-hoc analysis with Bonferroni correction. As a result, 174 nursing professionals were recruited, 79.3% female, average age 33.9 years. One-third belonged to the Metropolitan Region of Chile. The highest psychosocial risk was obtained by nurses over 30 years of age, from the Metropolitan Region, with more than 16 patients under their care, at the hospital or psychiatric emergency level. Significant differences were observed in work overload and psychosocial risks according to personal and work characteristics of the professionals, as well as of the users and health services. The levels of psychosocial risk and work overload of mental health and psychiatric nurses were reported, as well as the comparison of these according to personal, sociodemographic, and work characteristics. In order to improve the quality of work life of these professionals and the quality of these services, it is essential to develop interventions focused on the dimensions addressed, as well as to define norms and policies that ensure a workload in accordance with international standards., (© 2024 John Wiley & Sons Australia, Ltd.)

Defining the subset of cellular factors governing SARS-CoV-2 replication can provide critical insights into viral pathogenesis and identify targets for host-directed antiviral therapies. While a number of genetic screens have previously reported SARS-CoV-2 host dependency factors, these approaches relied on utilizing pooled genome-scale CRISPR libraries, which are biased towards the discovery of host proteins impacting early stages of viral replication. To identify host factors involved throughout the SARS-CoV-2 infectious cycle, we conducted an arrayed genome-scale siRNA screen. Resulting data were integrated with published datasets to reveal pathways supported by orthogonal datasets, including transcriptional regulation, epigenetic modifications, and MAPK signalling. The identified proviral host factors were mapped into the SARS-CoV-2 infectious cycle, including 27 proteins that were determined to impact assembly and release. Additionally, a subset of proteins were tested across other coronaviruses revealing 17 potential pan-coronavirus targets. Further studies illuminated a role for the heparan sulfate proteoglycan perlecan in SARS-CoV-2 viral entry, and found that inhibition of the non-canonical NF-kB pathway through targeting of BIRC2 restricts SARS-CoV-2 replication both in vitro and in vivo . These studies provide critical insight into the landscape of virus-host interactions driving SARS-CoV-2 replication as well as valuable targets for host-directed antivirals., Competing Interests: COMPETING INTERESTS STATEMENT J.F.H. has received research support, paid to Northwestern University, from Gilead Sciences, and is a paid consultant for Merck. The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus, Pfizer and Prosetta, outside of the reported work. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, Astrazeneca and Novavax. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. All other authors declare no competing interests.

Background: Magnetic resonance imaging (MRI) scans are known to suffer from a variety of acquisition artifacts as well as equipment-based variations that impact image appearance and segmentation performance. It is still unclear whether a direct relationship exists between magnetic resonance (MR) image quality metrics (IQMs) (e.g., signal-to-noise, contrast-to-noise) and segmentation accuracy., Purpose: Deep learning (DL) approaches have shown significant promise for automated segmentation of brain tumors on MRI but depend on the quality of input training images. We sought to evaluate the relationship between IQMs of input training images and DL-based brain tumor segmentation accuracy toward developing more generalizable models for multi-institutional data., Methods: We trained a 3D DenseNet model on the BraTS 2020 cohorts for segmentation of tumor subregions enhancing tumor (ET), peritumoral edematous, and necrotic and non-ET on MRI; with performance quantified via a 5-fold cross-validated Dice coefficient. MRI scans were evaluated through the open-source quality control tool MRQy, to yield 13 IQMs per scan. The Pearson correlation coefficient was computed between whole tumor (WT) dice values and IQM measures in the training cohorts to identify quality measures most correlated with segmentation performance. Each selected IQM was used to group MRI scans as "better" quality (BQ) or "worse" quality (WQ), via relative thresholding. Segmentation performance was re-evaluated for the DenseNet model when (i) training on BQ MRI images with validation on WQ images, as well as (ii) training on WQ images, and validation on BQ images. Trends were further validated on independent test sets derived from the BraTS 2021 training cohorts., Results: For this study, multimodal MRI scans from the BraTS 2020 training cohorts were used to train the segmentation model and validated on independent test sets derived from the BraTS 2021 cohort. Among the selected IQMs, models trained on BQ images based on inhomogeneity measurements (coefficient of variance, coefficient of joint variation, coefficient of variation of the foreground patch) and the models trained on WQ images based on noise measurement peak signal-to-noise ratio (SNR) yielded significantly improved tumor segmentation accuracy compared to their inverse models., Conclusions: Our results suggest that a significant correlation may exist between specific MR IQMs and DenseNet-based brain tumor segmentation performance. The selection of MRI scans for model training based on IQMs may yield more accurate and generalizable models in unseen validation., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Introduction: Human saliva was used to develop non-invasive liquid biopsy biomarkers to establish saliva as an alternate to blood and plasma in translational research. The present study focused on understanding the impact of sample storage conditions on the extraction of RNA from saliva and the RNA yield, to be applied in clinical diagnosis. In this study, genes related to asthma were used to test the method developed. Methods: Salivary RNA was extracted from three subjects using the Qiazol ® based method and quantified by both spectrophotometric (NanoDrop) and fluorometric (Qubit ® ) methods. RNA integrity was measured using a bioanalyzer. Quantitative PCR was used to monitor the impact of storage conditions on the expression of housekeeping genes: GAPDH and β-actin, and the asthma related genes: POSTN and FBN2 . In addition, an independent cohort of 38 asthmatics and 10 healthy controls were used to validate the expression of POSTN and FBN2 as mRNA salivary biomarkers. Results: Approximately 2 µg of total RNA was obtained from the saliva stored at 40°C without any preservative for 2 weeks showing consistent gene expression with RNA stored at room temperature (RT) for 48 h with RNA later . Although saliva stored with RNA later showed a substantial increase in the yield (110 to 234 ng/μL), a similar Cq (15.6 ± 1.4) for the 18s rRNA gene from saliva without preservative showed that the RNA was stable enough. Gene expression analysis from the degraded RNA can be performed by designing the assay using a smaller fragment size spanning a single exon as described below in the case of the POSTN and FBN2 genes in the asthma cohort. Conclusion: This study showed that samples stored at room temperature up to a temperature of 40°C without any preservative for 2 weeks yielded relatively stable RNA. The methodology developed can be employed to transport samples from the point of collection to the laboratory, under non-stringent storage conditions enabling the execution of gene expression studies in a cost effective and efficient manner., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bhamidimarri, Fuentes, Salameh, Mahboub and Hamoudi.)

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.

Purpose: The quality of radiotherapy auto-segmentation training data, primarily derived from clinician observers, is of utmost importance. However, the factors influencing the quality of clinician-derived segmentations are poorly understood; our study aims to quantify these factors., Methods: Organ at risk (OAR) and tumor-related segmentations provided by radiation oncologists from the Contouring Collaborative for Consensus in Radiation Oncology data set were used. Segmentations were derived from five disease sites: breast, sarcoma, head and neck (H&N), gynecologic (GYN), and GI. Segmentation quality was determined on a structure-by-structure basis by comparing the observer segmentations with an expert-derived consensus, which served as a reference standard benchmark. The Dice similarity coefficient (DSC) was primarily used as a metric for the comparisons. DSC was stratified into binary groups on the basis of structure-specific expert-derived interobserver variability (IOV) cutoffs. Generalized linear mixed-effects models using Bayesian estimation were used to investigate the association between demographic variables and the binarized DSC for each disease site. Variables with a highest density interval excluding zero were considered to substantially affect the outcome measure., Results: Five hundred seventy-four, 110, 452, 112, and 48 segmentations were used for the breast, sarcoma, H&N, GYN, and GI cases, respectively. The median percentage of segmentations that crossed the expert DSC IOV cutoff when stratified by structure type was 55% and 31% for OARs and tumors, respectively. Regression analysis revealed that the structure being tumor-related had a substantial negative impact on binarized DSC for the breast, sarcoma, H&N, and GI cases. There were no recurring relationships between segmentation quality and demographic variables across the cases, with most variables demonstrating large standard deviations., Conclusion: Our study highlights substantial uncertainty surrounding conventionally presumed factors influencing segmentation quality relative to benchmarks.

Contrast enhanced pulmonary vein magnetic resonance angiography (PV CE-MRA) has value in atrial ablation pre-procedural planning. We aimed to provide high fidelity, ECG gated PV CE-MRA accelerated by variable density Cartesian sampling (VD-CASPR) with image navigator (iNAV) respiratory motion correction acquired in under 4 min. We describe its use in part during the global iodinated contrast shortage. VD-CASPR/iNAV framework was applied to ECG-gated inversion and saturation recovery gradient recalled echo PV CE-MRA in 65 patients (66 exams) using .15 mmol/kg Gadobutrol. Image quality was assessed by three physicians, and anatomical segmentation quality by two technologists. Left atrial SNR and left atrial/myocardial CNR were measured. 12 patients had CTA within 6 months of MRA. Two readers assessed PV ostial measurements versus CTA for intermodality/interobserver agreement. Inter-rater/intermodality reliability, reproducibility of ostial measurements, SNR/CNR, image, and anatomical segmentation quality was compared. The mean acquisition time was 3.58 ± 0.60 min. Of 35 PV pre-ablation datasets (34 patients), mean anatomical segmentation quality score was 3.66 ± 0.54 and 3.63 ± 0.55 as rated by technologists 1 and 2, respectively (p = 0.7113). Good/excellent anatomical segmentation quality (grade 3/4) was seen in 97% of exams. Each rated one exam as moderate quality (grade 2). 95% received a majority image quality score of good/excellent by three physicians. Ostial PV measurements correlated moderate to excellently with CTA (ICCs range 0.52-0.86). No difference in SNR was observed between IR and SR. High quality PV CE-MRA is possible in under 4 min using iNAV bolus timing/motion correction and VD-CASPR., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Breast cancer, a global health concern affecting women, has been linked to alterations in the gut microbiota, impacting various aspects of human health. This study investigates the interplay between breast cancer and the gut microbiome, particularly focusing on colonization resistance-an essential feature of the microbiota's ability to prevent pathogenic overgrowth. Using a mouse model of breast cancer, we employ diversity analysis, co-occurrence network analysis, and robustness tests to elucidate the impact of breast cancer on microbiome dynamics. Our results reveal that breast cancer exposure affects the bacterial community's composition and structure, with temporal dynamics playing a role. Network analysis demonstrates that breast cancer disrupts microbial interactions and decreases network complexity, potentially compromising colonization resistance. Moreover, network robustness analysis shows the susceptibility of the microbiota to node removal, indicating potential vulnerability to pathogenic colonization. Additionally, predicted metabolic profiling of the microbiome highlights the significance of the enzyme EC 6.2.1.2 - Butyrate--CoA ligase, potentially increasing butyrate, and balancing the reduction of colonization resistance. The identification of Rubrobacter as a key contributor to this enzyme suggests its role in shaping the microbiota's response to breast cancer. This study uncovers the intricate relationship between breast cancer, the gut microbiome, and colonization resistance, providing insights into potential therapeutic strategies and diagnostic approaches for breast cancer patients., 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 Author(s).)

The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy-to-degrade components accumulate during early-stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass-loss rates and stabilization, notably in colder locations. Using TBI improved mass-loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early-stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models., (© 2024 The Authors. Ecology Letters published by John Wiley & Sons Ltd.)

Introduction: The internal representation of verticality could be disturbed when a lesion in the central nervous system (CNS) affects the centers where information from the vestibular, visual, and/or somatosensory systems, increasing the risk of falling., Objective: The aim was to evaluate the vestibular and somatosensory contribution to the verticality pattern in patients with stroke and other neurological disorders., Methods: A literature search was performed in PubMed, Scopus, Web of Science, and CINAHL databases. Cross-sectional, case-control, and cohort studies comparing body verticality in patients with stroke or CNS diseases (CNSD) versus healthy controls were selected. Subjective postural vertical (SPV) in roll and pitch planes was used as the primary variable., Results: Ten studies reporting data from 390 subjects were included. The overall effect for CNSD patients showed a misperception of body verticality in roll (standardized mean difference [SMD] = 1.05; 95% confidence interval [CI] .84-1.25) and pitch planes (SMD = 1.03; 95% CI .51-1.55). In subgroup analyses, a high effect was observed in the perception of SPV both in roll and pitch planes in stroke (p = .002) and other CNSD (p < .001)., Conclusion: These findings suggest a potential misperception of SPV in patients with stroke and other neurological disturbances. Patients with CNSD could present an alteration of vestibular and somatosensory contribution to verticality construction, particularly stroke patients with pusher syndrome (PS), followed by those with PS combined with hemineglect., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Latinxs are vastly underrepresented in mental health research; one of many contributing factors may be complexities in the research consent process, including language preferences. We examined determinants of comprehension of research consent procedures and tested the effects of a preconsent research schema condition among 180 adults with schizophrenia (60 Latinx-English and 60 Latinx-Spanish preference, and 60 non-Latinx White)., Study Design: Participants were randomly assigned (equal allocation) to an educational session regarding clinical research concepts and processes (schema condition) or to an attention control. Following a subsequent simulated consent procedure for a hypothetical drug trail, comprehension of consent disclosures was measured with 2 standard measures., Study Results: One-way ANOVAs showed significant medium effect size differences between ethnicity/language groups on both measures of comprehension (η2s = 0.066-0.070). The Latinx-Spanish group showed lower comprehension than non-Latinx White participants; differences between the 2 Latinx groups did not reach statistical significance. Group differences were not statistically significant after adjusting for differences in education, or on scores from structured measures of acculturation, health literacy, or research literacy. Two-way ANOVAs showed no significant main effects for consent procedure on either comprehension measure (Ps > .369; partial η2s < 0.006) and no significant group-by-consent interactions (Ps > .554; partial η2s < 0.008)., Conclusions: Although the preconsent procedure was not effective, the results suggest health and research literacy may be targets for reducing disparities in consent comprehension. The onus is on researchers to improve communication of consent information as an important step to addressing health care disparities., (Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2023.)

Competing Interests: K.A.W. serves as an Editorial Board Member for Physics and Imaging in Radiation Oncology. C.D.F. has received travel, speaker honoraria, and/or registration fee waivers unrelated to this project from The American Association for Physicists in Medicine, the University of Alabama-Birmingham, The American Society for Clinical Oncology, The Royal Australian and New Zealand College of Radiologists, The American Society for Radiation Oncology, The Radiologic Society of North America, and The European Society for Radiation Oncology. The other authors have no interests to disclose. During the preparation of this work, the authors used ChatGPT (GPT-4 architecture; ChatGPT September 25 Version) to improve the grammatical accuracy and semantic structure of portions of the text. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Cancer remains a worldwide cause of morbidity and mortality. Investigational research efforts have included the administration of tumor-derived extracts to healthy animals. Having previously demonstrated that the administration of non-transmissible, human cancer-derived homogenates induced malignant tumors in mice, here, we examined the consequences of administering 50 or 100 µg of protein of crude homogenates from mammary carcinoma, pancreatic adenocarcinoma, and melanoma samples in 6 inoculations per week during 2 months. The concurrent control mice received homogenates of healthy donor-skin cosmetic surgery fragments. Mammary carcinoma homogenate administration did not provoke the deterioration or mortality of the animals. Multiple foci of lung adenocarcinomas with a broad expression of malignity histomarkers coexisting with small cell-like carcinomas were found. Disseminated cells, positive to classic epithelial markers, were detected in lymphoid nodes. The administration of pancreatic tumor and melanoma homogenates progressively deteriorated animal health. Pancreatic tumor induced poorly differentiated lung adenocarcinomas and pancreatic islet hyperplasia. Melanoma affected lungs with solid pseudopapillary adenocarcinomas. Giant atypical hepatocytes were also observed. The kidney exhibited dispersed foci of neoplastic cells within a desmoplastic matrix. Nuclear overlapping with hyperchromatic nuclei, mitotic figures, and prominent nuclear atypia was identified in epidermal cells. None of these changes were ever detected in the control mice. Furthermore, the incubation of zebrafish embryos with breast tumor homogenates induced the expression of c-M yc and HER-2 as tumor markers, contrasting to embryos exposed to healthy tissue-derived material. This study confirms and extends our hypothesis that tumor homogenates contain and may act as vectors for "malignancy drivers," which ultimately implement a carcinogenesis process in otherwise healthy mice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Berlanga-Acosta, Arteaga-Hernandez, Garcia-Ojalvo, Duvergel-Calderin, Rodriguez-Touseiro, Lopez-Marin, Suarez-Alba, Fuentes-Morales, Mendoza-Fuentes, Fernández-Puentes, Nuñez-Figueredo and Guillen-Nieto.)

Background: The treatment planning process from segmentation to producing a deliverable plan is time-consuming and labor-intensive. Existing solutions automate the segmentation and planning processes individually. The feasibility of combining auto-segmentation and auto-planning for volumetric modulated arc therapy (VMAT) for rectal cancers in an end-to-end process is not clear., Purpose: To create and clinically evaluate a complete end-to-end process for auto-segmentation and auto-planning of VMAT for rectal cancer requiring only the gross tumor volume contour and a CT scan as inputs., Methods: Patient scans and data were retrospectively selected from our institutional records for patients treated for malignant neoplasm of the rectum. We trained, validated, and tested deep learning auto-segmentation models using nnU-Net architecture for clinical target volume (CTV), bowel bag, large bowel, small bowel, total bowel, femurs, bladder, bone marrow, and female and male genitalia. For the CTV, we identified 174 patients with clinically drawn CTVs. We used data for 18 patients for all structures other than the CTV. The structures were contoured under the guidance of and reviewed by a gastrointestinal (GI) radiation oncologist. The predicted results for CTV in 35 patients and organs at risk (OAR) in six patients were scored by the GI radiation oncologist using a five-point Likert scale. For auto-planning, a RapidPlan knowledge-based planning solution was modeled for VMAT delivery with a prescription of 25 Gy in five fractions. The model was trained and tested on 20 and 34 patients, respectively. The resulting plans were scored by two GI radiation oncologists using a five-point Likert scale. Finally, the end-to-end pipeline was evaluated on 16 patients, and the resulting plans were scored by two GI radiation oncologists., Results: In 31 of 35 patients, CTV contours were clinically acceptable without necessary modifications. The CTV achieved a Dice similarity coefficient of 0.85 (±0.05) and 95% Hausdorff distance of 15.25 (±5.59) mm. All OAR contours were clinically acceptable without edits, except for large and small bowel which were challenging to differentiate. However, contours for total, large, and small bowel were clinically acceptable. The two physicians accepted 100% and 91% of the auto-plans. For the end-to-end pipeline, the two physicians accepted 88% and 62% of the auto-plans., Conclusions: This study demonstrated that the VMAT treatment planning technique for rectal cancer can be automated to generate clinically acceptable and safe plans with minimal human interventions., (© 2024 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

A new eusdesmane sesquiterpenoid, characterized as 3,5,8a-trimethyl-8-oxo-4,4a,5,6,7,8,8a,9-octahydronaphtho[2,3- b ]furan-5-yl acetate ( 1 ), has been isolated from the rhizomes of the South African variety of wild ginger ( Siphonochilus aethiopicus (Schweinf) B. L. Burtt). The compound was obtained by silica gel column chromatography. Its structure was elucidated by nuclear magnetic resonance spectroscopy (NMR) and mass-spectrometric (MS) analyses, including 1D-, 2D-NMR, and HR-LCMS. We also investigated the cytotoxic effect of 1 on a panel of cancer cell lines, human breast, pancreas, lung, colon, and central nervous system cancer lines. The data are not encouraging since its antitumor effect is poor. Nonetheless, the discovery of new molecules may provide a source of new compounds with important biological effects applicable to the field of medicine., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Although considered one of the most pristine ecosystems, Antarctica has been largely influenced by human activities during the last 50 years, affecting its unique biodiversity. One of the major global threats to health is the emergence of antibiotic-resistant bacteria that may be actively transferred to wildlife. We cultured and tested for antibiotic resistance in 137 cloacal and fresh fecal samples of several avian and marine mammal species from the Antarctic Peninsula, the most impacted area in Antarctica. Alarmingly, 80 % of the isolates showed antibiotic resistance, either phenotypically or genotypically. Most of the resistant bacteria, such as Enterobacteriaceae and Enterococcus species, are part of local gastrointestinal microbiota. Penguins and pinnipeds harbored a great diversity of antibiotic resistance and must be eligible as sentinels for future studies. These results show that antibiotic resistance has rapidly transferred to bacteria in Antarctic wildlife, which is a global matter of concern., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Carbapenemase-producing Citrobacter freundii has been reported as a leading cause of healthcare-associated infections. Particularly, C. freundii belonging to the sequence type (ST) 18 is considered to be an emerging nosocomial clone., Objectives: To report the genomic background and phylogenomic analysis of a multidrug-resistant NDM-1-producing C. freundii ST18 (strain CF135931) isolated from an endangered green sea turtle affected by plastic pollution in Brazil., Methods: Genomic DNA was extracted and sequenced using the Illumina NextSeq platform. De novo assembly was performed by CLC Workbench, and in silico analysis accomplished by bioinformatics tools. For phylogenomic analysis, publicly available C. freundii (txid:546) genome assemblies were retrieved from the NCBI database., Results: The genome size was calculated at 5 290 351 bp, comprising 5263 total genes, 4 rRNAs, 77 tRNAs, 11ncRNAs, and 176 pseudogenes. The strain belonged to C. freundii ST18, whereas resistome analysis predicted genes encoding resistance to β-lactams (bla NDM-1 , bla OXA-1 , bla CMY-117 , and bla TEM-1C ), aminoglycosides (aph(3'')-Ib, aadA16, aph(3')-VI, aac(6')-Ib-cr, and aph(6)-Id), quinolones (aac(6')-Ib-cr), macrolides (mph(A) and erm(B)), sulphonamides (sul1 and sul2), tetracyclines (tetA and tetD), and trimethoprim (dfrA27). The phylogenomic analysis revealed that CF135931 strain is closely related to international human-associated ST18 clones producing NDM-1., Conclusion: Genomic surveillance efforts are necessary for robust monitoring of the emergence of drug-resistant strains and WHO critical priority pathogens within a One Health framework. In this regard, this draft genome and associated data can improve understanding of dissemination dynamics of nosocomial clones of carbapenemase-producing C. freundii beyond hospital walls. In fact, the emergence of NDM-1-producing C. freundii of global ST18 in wildlife deserves considerable attention., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The COVID-19 pandemic had a significant impact on the mental health of the population. The lockdown period in Spain - from March 14 to June 21, 2020 - was particularly stressful. This study aims to examine the differences in visits to the emergency department for psychiatric reasons before and during the lockdown period in a hospital in the province of Lleida (Catalonia, Spain), which has a catchment area of 431,183 inhabitants. We hope that this study can contribute to the understanding of this difficult period in our recent history and help us to be prepared in case of new social emergencies that may affect the mental health of the general population. Aims: This study aims to examine the differences in ER visits due to psychiatric reasons before and during the COVID-19 lockdown period in a province hospital in Spain. Methods: We compared the n = 1,599 visits to the emergency room and their characteristics before (June 13 to March 13, 2020) and during (March 14 to June 21, 2020) the lockdown period in the province of Lerida, Spain. Data were obtained from the electronic health records. Information collected included sociodemographic variables, reason for consultation, previous diagnosis, and characteristics of suicidal ideation and attempts - including history of previous suicidal behavior, method, days spent in the ER, suicide reattempts at 6-month follow-up. Results: Before lockdown, there were an average of 11.2 psychiatric emergencies per day compared with 9.2 psychiatric emergencies per day during lockdown. Regarding suicidal behavior, before lockdown, there were an average of 0.9 suicide attempts before lockdown compared with 0.7 attempts per day during lockdown. Limitations: Since the data came from the electronic health records, we have relied on the clinical diagnosis made by different psychiatrists. Also, we did not record psychiatric comorbidities, but instead only registered one main Axis I diagnosis and one main Axis II diagnosis. Conclusions: We observed a decrease in the number of visits to the ER in general, as well as a lower frequency of patients with suicidal behavior during the first and only lockdown period in Spain, which occurred during the initial months of the pandemic. This is consistent with previous studies showing a reduction of suicidal behavior during periods of social emergency. However, this decrease could be only temporary, and several authors predict an increase of suicidal behavior in the aftermath of the COVID-19 crisis. Ensuring access to mental healthcare during periods of crisis is crucial for the population.

Competing Interests: Clifton D. Fuller has received unrelated direct industry grant/in-kind support, honoraria, and travel funding from Elekta AB.

A successful choice of post-mining restoration activities in dry climates may depend on relevant features related to topographic characteristics, hydrological processes and vegetation development, which will determine functional recovery in these ecosystems. The combination of different restoration techniques to reestablish vegetation, such as sowing and plantation, implies the interspersion of bare-soil areas with vegetated areas in early plant development stages, which may result in an associated mosaic of hydrologic functioning. In this study, we conducted a drone-based assessment to disentangle the role played by microsite-scale hydrological processes (i.e., planting hole slope, sink volume capacity, individual catchment area, Flow Length Index) promoted by restoration actions in soil protection and vegetation development on the hillside scale. Based on two contrasting restoration scenarios (Steep hillside and Smooth hillside), the different applied restoration treatments conditioned the microtopographic processes on the planting hole scale and, therefore, resource redistribution. The main results showed higher planting hole functionality on the smooth hillsides than on steep hillside, which resulted in greater water availability and bigger vegetation patches. By addressing the role of hydrological processes on the microsite scale, our study contributes substantially to prior knowledge on the relevant factors for ecosystem development and post-mining restoration success. It also demonstrates that high-resolution drone images can be a very useful tool for monitoring restoration actions, especially in large, inaccessible and unstable restored areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A mathematical concept, n-tuples are originally applied to medicinal chemistry, especially with the creation of scaffold diversity inspired by the hybridisation of different commercial drugs with cytarabine, a synthetic arabinonucleoside derived from two marine natural products, spongouridine and spongothymidine. The new methodology explores the virtual chemical-factorial combination of different commercial drugs (immunosuppressant, antibiotic, antiemetic, anti-inflammatory, and anticancer) with the anticancer drug cytarabine. Real chemical combinations were designed and synthesised for 8-duples, obtaining a small representative library of interesting organic molecules to be biologically tested as proof of concept. The synthesised library contains classical molecular properties regarding the Lipinski rules and/or beyond rules of five (bRo5) and is represented by the covalent combination of the anticancer drug cytarabine with ibuprofen, flurbiprofen, folic acid, sulfasalazine, ciprofloxacin, bortezomib, and methotrexate. The insertion of specific nomenclature could be implemented into artificial intelligence algorithms in order to enhance the efficiency of drug-hunting programs. The novel methodology has proven useful for the straightforward synthesis of most of the theoretically proposed duples and, in principle, could be extended to any other central drug.

Aortic arch surgery is a surgical challenge due to its technical complexity and brain and body protection requirements., Aim: To describe the surgical protocol and the short and long-term results of aortic arch replacement surgery in a center in the metropolitan region of Santiago, Chile., Methods: Retrospective descriptive study from April 2015 to August 2022. Elective, urgent, and emergency patients were included, with diagnoses of arch aneurysm and acute or chronic type I and II DeBakey aortic dissection., Technique: Arterial cannulation at the brachiocephalic trunk, right axillary artery, or directly into the true lumen of the aortic dissection with Seldinger technique, guided by epiaortic and transesophagic ultrasound. Deep hypothermia at 24°C. Uni or bilateral antegrade cerebral perfusion according to runoff. Four devices were used: a straight tube, a tube with 3 or 4 branches, and a frozen elephant trunk., Results: 37 patients were operated on; 24 of them were men. The average age was 57 years old. In seven patients, a straight tube with anastomosis was used with anastomosis on the island; in six patients, a tube with 3 branches; in ten patients, a tube with four branches; and in fourteen patients, a frozen elephant trunk. There were twenty-one patients (57%) with associated morbidity: prolonged mechanical ventilation 14 the most frequent, paralysis chordae in 7 patients; there were six neurological morbidities, one of them permanent, renal dysfunction in 5 patients, pneumonia associated with mechanical ventilation in 4 patients, reoperation due to bleeding in 4. There was no associated cardiac morbidity. Operative and global mortality at 30 days was 13.5%. Follow-up was closed in October 2022 and is complete in the 30 survivors; the average was 20 months. Two patients died in the follow-up at five years; the survival in the follow-up was 90%., Conclusion: The management protocol has good results regarding morbidity and mortality, similar to the international series.

Among the most harmful tumors detected in the human body, such as breast, colon, brain or pancreas, breast (BC) and colorectal cancer (CRC) are the first and third most frequent cancer worldwide, respectively. The current existing chemotherapeutic treatments present serious side effects due to their intravenous administration can induce cytotoxicity in healthy cells. Thus, new treatment methods based on drug-loaded polymeric nanofibers (NFs) have gained significant potential for their use in localized cancer chemotherapy. Here, a deep in vitro comparative analysis between maslinic acid (MA) and a tyramine-maslinic acid (TMA) derivative is initially performed. This analysis includes a proliferation, and a cell cycle assay, and a genotoxicity, antiangiogenic and apoptosis study. Then, the TMA derivative has been incorporated into electrospun polymeric NFs obtaining an implantable dressing material with antitumor activity. Two types of patches containing TMA-loaded polymeric NFs of poly(caprolactone) (PCL), and a mixture of polylactic acid/poly(4-vinylpyridine) (PLA/PVP) were fabricated by the electrospinning technique. The characterization of the drug-loaded NFs showed an encapsulation capacity of 0.027 mg TMA/mg PCL and 0.024 mg TMA/mg PLA/PVP. Then, the cytotoxic activity of both polymeric systems was tested in CRC (T84), BC (MCF-7) and a no tumor (L929) cell lines exposed to TMA-loaded NFs and blank NFs for 48 h. Moreover, cell cycle assay, genotoxicity, angiogenesis and apoptosis tests were carried out to study the mechanism of action of TMA. Blank NFs showed no-toxicity in all cell lines tested and both drug-loaded NFs significantly reduced cell proliferation (relative proliferation of ≈44 % and ≈25 % respectively). Therefore, TMA was less genotoxic than maslinic acid (MA), and reduced VEGFA expression in MCF-7 cells (1.32 and 2.12-fold for MA and TMA respectively). These results showed that TMA-loaded NFs could constitute a promising biocompatible and biodegradable nanoplatform for the local treatment of solid tumors such as CRC or BC., 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.)

Core organizational values are essential for any organization, including academic institutions. Formal and informal leaders can have a positive, or negative, impact on shaping their culture through the core values. Members of an organization, including students, can be shaped by the organizational values in ways that strengthen, or impede, their professional identity formation. Here, we discuss the use of organizational values as vital substrates needed to shape the desired behaviors and attitudes that will help describe the organizational culture and identity. We define and discuss various types of core values, identify the benefits and challenges of core values alignment, and offer strategies for leaders at all levels to reflect on their own organization's core values and their current approach to their contribution to an effective and sustainable workplace that supports the professional identity formation of all members., Competing Interests: Declaration of Competing Interest None declared., (Published by Elsevier Inc.)

Stenotrophomonas maltophilia is an opportunistic human pathogen associated with nosocomial and community-acquired infections. We have conducted a microbiological and genomic surveillance study of broad-spectrum cephalosporin- and carbapenem-resistant Gram-negative bacteria colonizing wild birds inhabiting the Brazilian Amazonia. Strikingly, two S. maltophilia strains (SM79 and SM115) were identified in Plain-throated antwren (Isleria hauxwelli) passerines affected by Amazonian fragmentation and degradation. Noteworthy, SM79 and SM115 strains belonged to new sequence types (STs) ST474 and ST473, respectively, displaying resistance to broad-spectrum β-lactams, aminoglycosides and/or fluoroquinolones. In this regard, resistome analysis confirmed efflux pumps (smeABC, smeDEF, emrAB-tolC and macB), bla L1 and bla L2 , aph(3')-IIc and aac(6')-Iak, and Smqnr resistance genes. Comparative phylogenomic analysis with publicly available S. maltophilia genomes clustered ST473 and ST474 with human strains, whereas the ST474 was also grouped with S. maltophilia strains isolated from water and poultry samples. In summary, we report two novel sequence types of S. maltophilia colonizing wild Amazonian birds. The presence of opportunistic multidrug-resistant pathogens in wild birds, from remotes areas, could represent an ecological problem since these animals could easily promote long-distance dispersal of medically important antimicrobial-resistant bacteria. Therefore, while our results could provide a baseline for future epidemiological genomic studies, considering the limited information regarding S. maltophilia circulating among wild animals, additional studies are necessary to evaluate the clinical impact and degree of pathogenicity of this human opportunistic pathogen in wild birds., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of the Study: A prospective, randomized, double-blind study was designed to assess differences in brain relaxation between 20% mannitol and 3% hypertonic saline (HS) during elective supratentorial brain tumour surgery in patients with midline shift., Material and Methods: Sixty patients undergoing supratentorial craniotomy for tumour resection were enrolled to receive either 5mL/kg of 20% mannitol (n=30) or 3% HS (n=30) administered at skin incision. P CO2 in arterial blood was maintained within 35-40mmHg and arterial blood pressure was controlled within baseline values ±20%. The primary outcome was the proportion of satisfactory brain relaxation. The surgeon assessed brain relaxation on a four-point scale (1=excellent with no swelling, 2=minimal swelling, 3=serious swelling not requiring treatment, 4=severe swelling requiring treatment). Postsurgical intracranial changes determined by imaging techniques, postoperative complications, PACU and hospital stay, and mortality at 30 days were also recorded. Appropriate statistical tests were used for comparison; P<0.05 was considered as significant. This trial was registered in Eudract.ema.europa.eu (#2021-006290-40)., Results: There was no difference in brain relaxation: 2.00 [1.00-2.00] and 2.00 [1.75-3.00] for patients in mannitol and HS groups, respectively (P=0.804). Tumour size (OR: 0.99, 95% CI: 0.99-1.01; P=0.371), peritumoral oedema classification (OR: 0.57, 95% CI: 0.11-2.84; P=0.493), mass effect (OR: 0.86, 95% CI: 0.16-4.87; P=0.864), anaesthesia (OR: 4.88, 95% CI: 0.82-28.96; P=0.081) and midline shift (OR: 5.00, 95% CI: 0.84-29.70; P=0.077) did not have a significant influence on brain swelling in patients treated with either mannitol or HS. No significant differences in perioperative outcomes, mortality and length of PACU and hospital stay were observed., Conclusions: 5mL/kg of 20% mannitol or 3% HS result in similar brain relaxation scores in patients undergoing craniotomy for supratentorial brain tumour with midline shift., (Copyright © 2022 Sociedad Española de Neurocirugía. Published by Elsevier España, S.L.U. All rights reserved.)

Importance: Candida glabrata is a major fungal pathogen, which is able to lose mitochondria and form small and slow-growing colonies, called "petite." This attenuated growth rate has created controversies and questioned the clinical importance of petiteness. Herein, we have employed multiple omics technologies and in vivo mouse models to critically assess the clinical importance of petite phenotype. Our WGS identifies multiple genes potentially underpinning petite phenotype. Interestingly, petite C. glabrata cells engulfed by macrophages are dormant and, therefore, are not killed by the frontline antifungal drugs. Interestingly, macrophages infected with petite cells mount distinct transcriptomic responses. Consistent with our ex vivo observations, mitochondrial-proficient parental strains outcompete petites during systemic and gut colonization. Retrospective examination of C. glabrata isolates identified petite prevalence a rare entity, which can significantly vary from country to country. Collectively, our study overcomes the existing controversies and provides novel insights regarding the clinical relevance of petite C. glabrata isolates., Competing Interests: The authors declare no conflict of interest.

During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac ® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac ® ; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3-5 years old and headache in 6-17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac ® was safe and well tolerated in children and adolescents, with different safety patterns according to age.

Purpose: Treatment planning for craniospinal irradiation (CSI) is complex and time-consuming, especially for resource-constrained centers. To alleviate demanding workflows, we successfully automated the pediatric CSI planning pipeline in previous work. In this work, we validated our CSI autosegmentation and autoplanning tool on a large dataset from St. Jude Children's Research Hospital., Methods: Sixty-three CSI patient CT scans were involved in the study. Pre-planning scripts were used to automatically verify anatomical compatibility with the autoplanning tool. The autoplanning pipeline generated 15 contours and a composite CSI treatment plan for each of the compatible test patients (n=51). Plan quality was evaluated quantitatively with target coverage and dose to normal tissue metrics and qualitatively with physician review, using a 5-point Likert scale. Three pediatric radiation oncologists from 3 institutions reviewed and scored 15 contours and a corresponding composite CSI plan for the final 51 test patients. One patient was scored by 3 physicians, resulting in 53 plans scored total., Results: The algorithm automatically detected 12 incompatible patients due to insufficient junction spacing or head tilt and removed them from the study. Of the 795 autosegmented contours reviewed, 97% were scored as clinically acceptable, with 92% requiring no edits. Of the 53 plans scored, all 51 brain dose distributions were scored as clinically acceptable. For the spine dose distributions, 92%, 100%, and 68% of single, extended, and multiple-field cases, respectively, were scored as clinically acceptable. In all cases (major or minor edits), the physicians noted that they would rather edit the autoplan than create a new plan., Conclusions: We successfully validated an autoplanning pipeline on 51 patients from another institution, indicating that our algorithm is robust in its adjustment to differing patient populations. We automatically generated 15 contours and a comprehensive CSI treatment plan for each patient without physician intervention, indicating the potential for increased treatment planning efficiency and global access to high-quality radiation therapy., Competing Interests: HB is currently employed by the company Varian Medical Affairs, with a sessional lecturing position at the University of Cape Town. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hernandez, Burger, Nguyen, Paulino, Lucas, Faught, Duryea, Netherton, Rhee, Cardenas, Howell, Fuentes, Pollard-Larkin, Court and Parkes.)

Aminoglycoside antimicrobials remain valuable therapeutic options, but their effectiveness has been threatened by the production of bacterial 16S ribosomal RNA methyltransferases (16S-RMTases). In this study, we evaluated the genomic epidemiology of 16S-RMTase genes among Gram-negative bacteria circulating in the American continent. A total of 4877 16S-RMTase sequences were identified mainly in Enterobacterales and nonfermenting Gram-negative bacilli isolated from humans, animals, foods, and the environment during 1931-2023. Most of the sequences identified were found in the United States, Brazil, Canada, and Mexico, and the prevalence of 16S-RMTase genes have increased in the last five years (2018-2022). The three species most frequently carrying 16S-RMTase genes were Acinetobacter baummannii , Klebsiella pneumoniae , and Escherichia coli . The armA gene was the most prevalent, but other 16S-RMTase genes (e.g., rmtB , rmtE , and rmtF ) could be emerging backstage. More than 90% of 16S-RMTase sequences in the Americas were found in North American countries, and although the 16S-RMTase genes were less prevalent in Central and South American countries, these findings may be underestimations due to limited genomic data. Therefore, whole-genome sequence-based studies focusing on aminoglycoside resistance using a One Health approach in low- and middle-income countries should be encouraged.