Suitable Mouse Model to Study Dynamics of West Nile Virus Infection in Culex quinquefasciatus Mosquitoes.

West Nile Virus (WNV) poses a significant global public health threat as a mosquito-borne pathogen. While laboratory mouse models have historically played a crucial role in understanding virus biology, recent research has focused on utilizing immunocompromised models to study arboviruses like dengue and Zika viruses, particularly their interactions with Aedes aegypti mosquitoes. However, there has been a shortage of suitable mouse models for investigating WNV and St. Louis encephalitis virus interactions with their primary vectors, Culex spp. mosquitoes. Here, we establish the AG129 mouse (IFN α/ß/γ R-/-) as an effective vertebrate model for examining mosquito-WNV interactions. Following intraperitoneal injection, AG129 mice exhibited transient viremia lasting several days, peaking on the second or third day post-infection, which is sufficient to infect Culex quinquefasciatus mosquitoes during a blood meal. We also observed WNV replication in the midgut and dissemination to other tissues, including the fat body, in infected mosquitoes. Notably, infectious virions were present in the saliva of a viremic AG129 mouse 16 days post-exposure, indicating successful transmission capacity. These findings highlight the utility of AG129 mice for studying vector competence and WNV-mosquito interactions.

Significant Variability in Postoperative Thromboprophylaxis in Cushing's Disease Patients: A Survey of the North American Skull Base Society and the AANS/CNS Joint Tumor Section.

Introduction Cushing's disease (CD) is associated with hypercoagulability which is associated with an increased risk of venous thromboembolic events (VTEs) perioperatively. This risk persists even after successful transsphenoidal surgery (TSS). However, there are no current guidelines for pharmacologic thromboprophylaxis in this patient population. Objective Characterize existing thromboprophylaxis management practices in patients undergoing TSS for CD. Methods An anonymous RedCap survey comprised of questions about perioperative thromboprophylaxis in CD patients was distributed via the American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Tumor Section and the North American Skull Base Society (NASBS) email lists. Results The survey was distributed to 554 members of the AANS/CNS Joint Tumor Section and 1,094 members of NASBS asking that members who surgically treat CD respond. Sixty responses (3.0% response rate) were received. Fifty-two (86.7%) respondents are involved in the postoperative management of CD patients. Thirty-six (69.2%) treat all patients with postoperative VTE chemoprophylaxis, 8 (15.4%) treat some patients, while 8 (15.4%) do not use chemoprophylaxis. Preferred chemoprophylaxis varies as 26 (59.1%) administer low molecular weight heparin, 14 (31.8%) give unfractionated heparin, 1 (2.3%) give direct oral anticoagulants, and 3 (6.8%) give aspirin. Most (28, 53.8%) of the respondents perceive the VTE risk in this patient population to be 0 to 5%, 16 (30.8%) perceive the risk to be 6 to 10%, and 8 (15.4%) perceive it to be 11 to 20%. Conclusion There is great variability in VTE detection and postoperative prevention practice patterns in CD patients. This study highlights the need for prospective studies to clarify optimal pharmacologic chemoprophylaxis strategies and duration in this patient population.

The impact of ammonia on particle formation in the Asian Tropopause Aerosol Layer.

During summer, ammonia emissions in Southeast Asia influence air pollution and cloud formation. Convective transport by the South Asian monsoon carries these pollutant air masses into the upper troposphere and lower stratosphere (UTLS), where they accumulate under anticyclonic flow conditions. This air mass accumulation is thought to contribute to particle formation and the development of the Asian Tropopause Aerosol Layer (ATAL). Despite the known influence of ammonia and particulate ammonium on air pollution, a comprehensive understanding of the ATAL is lacking. In this modelling study, the influence of ammonia on particle formation is assessed with emphasis on the ATAL. We use the EMAC chemistry-climate model, incorporating new particle formation parameterisations derived from experiments at the CERN CLOUD chamber. Our diurnal cycle analysis confirms that new particle formation mainly occurs during daylight, with a 10-fold enhancement in rate. This increase is prominent in the South Asian monsoon UTLS, where deep convection introduces high ammonia levels from the boundary layer, compared to a baseline scenario without ammonia. Our model simulations reveal that this ammonia-driven particle formation and growth contributes to an increase of up to 80% in cloud condensation nuclei (CCN) concentrations at cloud-forming heights in the South Asian monsoon region. We find that ammonia profoundly influences the aerosol mass and composition in the ATAL through particle growth, as indicated by an order of magnitude increase in nitrate levels linked to ammonia emissions. However, the effect of ammonia-driven new particle formation on aerosol mass in the ATAL is relatively small. Ammonia emissions enhance the regional aerosol optical depth (AOD) for shortwave solar radiation by up to 70%. We conclude that ammonia has a pronounced effect on the ATAL development, composition, the regional AOD, and CCN concentrations.

Supporting Breastfeeding Exchange Relations by Building Equitable and Innovative Solutions: An Interview With João Aprigio Guerra de Almeida.

Professor Joao Aprigio Guerra de Almeida graduated in Food Engineering (UFV-1981) with a Master in Microbiology (UFV-1986) and a doctorate in Women's and Children's Health (Fiocruz/IFF, 1998) He is founder and coordinator of the Brazilian Human Milk Banks Network (Ministry of Health-Brasil/Oswaldo Cruz Foundation-Fiocruz, 1987 to 2024); Head of the National Reference Center for Human Milk Banks at the National Institute of Women, Children and Adolescent Health Fernandes Figueira-IFF (Fiocruz/IFF, 1987 to 2024); Executive Secretary of the Ibero-American Human Milk Banks Network Program (Ibero-American General Secretariat-SEGIB/Brazilian Cooperation Agency-ABC/MS-FIOCRUZ, 2008 to 2020); Coordinator of International Technical Cooperation in Human Milk Banks ABC/Fiocruz/MS (2005 to 2024); and Coordinator of the Human Milk Banks Network of the Community of Portuguese Speaking Countries - CPLP (2017 to 2024). He has been recognized with the Sasakawa Health Prize (World Health Organization [WHO], 2001); as Officer of the Order of Rio Branco (Presidency of the Federative Republic of Brazil, 2001); with Global Health Challenges and Responses of the South in Time of Crisis (WHO, 2009); as Commendator of the Order of Rio Branco-Ministry of Foreign Affairs/Presidency of the Federative Republic of Brazil (2018); and Dr LEE Jong-wook Memorial Prize for Public Health (WHO, 2020). His areas of activity include Public Health, breastfeeding, Human Milk Banks, Public Management, and International Technical Cooperation.

Sand smelt larvae's resilience to hypoxia and implications for thermal tolerance.

Deoxygenation is a growing threat to marine ecosystems, with an increase in the frequency, extent and intensity of hypoxia events in recent decades. These phenomena will pose various challenges to marine species, as it affects their survival, growth, body condition, metabolism and ability to handle other environmental stressors, such as temperature. Early life stages are particularly vulnerable to these changes. Thus, it is crucial to understand how these initial phases will respond to hypoxia to predict the impacts on marine populations and ecosystems. In this work, we aimed to evaluate the effect of oxygen (O2) availability on fitness related traits (mortality, growth and body condition), metabolism (Routine metabolic rates [RMR]) and thermal tolerance (CTmax), in early stages of Atherina presbyter, exposed for two weeks, to two O2 levels: normoxia (6.5-7.2 mg L-1) and hypoxia (2-2.5 mg L-1), through an experiment setup. Our findings showed that while low oxygen levels did not negatively impact mortality, total length, weight, or body condition (Fulton K), the larvae undergo metabolic depression when exposed to hypoxia, as an energy conservation mechanism. Furthermore, CTmax suffered a significant reduction in low O2 availability, due to the inability of the circulatory and respiratory systems to fulfill energy demands. These outcomes suggest that although early life stages of Atherina presbyter can survive under low oxygen environments, they are less capable of dealing with sudden increases in temperature when oxygen is scarce.

Enhancing metagenomic classification with compression-based features.

Metagenomics is a rapidly expanding field that uses next-generation sequencing technology to analyze the genetic makeup of environmental samples. However, accurately identifying the organisms in a metagenomic sample can be complex, and traditional reference-based methods may need to be more effective in some instances. In this study, we present a novel approach for metagenomic identification, using data compressors as a feature for taxonomic classification. By evaluating a comprehensive set of compressors, including both general-purpose and genomic-specific, we demonstrate the effectiveness of this method in accurately identifying organisms in metagenomic samples. The results indicate that using features from multiple compressors can help identify taxonomy. An overall accuracy of 95% was achieved using this method using an imbalanced dataset with classes with limited samples. The study also showed that the correlation between compression and classification is insignificant, highlighting the need for a multi-faceted approach to metagenomic identification. This approach offers a significant advancement in the field of metagenomics, providing a reference-less method for taxonomic identification that is both effective and efficient while revealing insights into the statistical and algorithmic nature of genomic data. The code to validate this study is publicly available at https://github.com/ieeta-pt/xgTaxonomy.

Estimating and planning hospital costs of public hospitals in Brazil.

While the estimate of hospital costs concerns the past, its planning focuses on the future. However, in many low and middle-income countries, public hospitals do not have robust accounting health systems to evaluate and project their expenses. In Brazil, public hospitals are funded based on government estimates of available hospital infrastructure, historical expenditures and population needs. However, these pieces of information are not always readily available for all hospitals. To solve this challenge, we propose a flexible simulation-based optimisation algorithm that integrates this dual task: estimating and planning hospital costs. The method was applied to a network of 17 public hospitals in Brazil to produce the estimates. Setting the model parameters for population needs and future hospital infrastructure can be used as a cost-projection tool for divestment, maintenance, or investment. Results show that the method can aid health managers in hospitals' global budgeting and policymakers in improving fairness in hospitals' financing.

A meta-analysis on alternative mating tactics: when the main and the alternative yield similar reproductive success.

In many species, individuals of the same sex exhibit different mating behaviours, a phenomenon known as alternative mating tactics (AMTs). These AMTs may occur in species in which morphology prevents individuals from adopting different tactics (fixed expression of AMTs) as well as in species in which individuals can alternate between them (flexible expression of AMTs). Regardless of the way different mating tactics are expressed, a key point to understanding the selective forces driving AMT evolution relies on identifying differences in the reproductive success between tactics. Empirical studies often indicate that individuals adopting the main tactic (generally the more aggressive) have higher mating success than those adopting the secondary tactic. However, while this is expected for species showing flexible expression of AMTs, the same should not hold for species showing fixed expression of AMTs. In species with fixed expression of AMTs, individuals adopting each tactic have morphological specialisations in acquiring mates that may be responsible for eliminating differences in reproductive success between tactics. Despite such expectations, a comprehensive investigation across species regarding differences in the reproductive success of AMTs is lacking. Using a meta-analytical approach, we investigated if there is a difference in the reproductive success between tactics and whether this difference is related to how these tactics are expressed (fixed or flexible). We focused on males since information on reproductive success for females with AMTs is still scarce. We hypothesised that (i) males adopting the main tactic have higher reproductive success than males adopting the secondary tactic, and (ii) the difference in reproductive success between tactics will be higher in species with flexible rather than fixed expression of AMTs. When all species were pooled, we found that males adopting the main tactic had a similar reproductive success to males adopting the secondary mating tactic. However, this trend changed between species with fixed and flexible expression of AMTs. In species with flexible expression of AMTs, males exhibiting the main tactic have higher mating success than those adopting secondary tactics, while in species with fixed expression of AMTs, males adopting distinct tactics have similar reproductive success. Thus, the widespread assumption that males adopting the main tactic have higher reproductive success than males adopting the secondary tactic may be restricted to species in which individuals can alternate between tactics during their lifespan. However, we found that most data on the reproductive success of males adopting AMTs is restricted to short reproductive windows and may not reflect differences in lifetime reproductive success between tactics. Therefore, we highlight the importance of examining the selective pressures associated with fixed and flexible expression of AMTs on lifetime reproductive success to attain a deeper understanding of AMT evolution.

A Chatbot-Like Platform to Enhance the Discovery of OMOP CDM Databases.

Multicentre studies become possible with the current strategies to solve the interoperability problems between databases. With the great adoption of those strategies, new problems regarding data discovery were raised. Some were solved using database catalogues and graphical dashboards for data analysis and comparison. However, when these communities grow, these strategies become obsolete. In this work, we addressed those challenges by proposing a platform with a chatbot-like mechanism to help medical researchers identify databases of interest. The tool was developed using the metadata extracted from OMOP CDM databases.

Venous Thromboembolism and Prevention Strategies in Patients with Cushing's Disease: A Systematic Review.

BACKGROUND: There is a well-documented association between Cushing's syndrome (CS) and hypercoagulability. However, there is limited data on the risk of venous thromboembolic events (VTEs) after surgery for Cushing's disease (CD). There is no consensus on optimal postoperative anticoagulation strategies in this group. This review gathers information on the rates of VTE after surgery for CD, as well as reported prophylaxis strategies in this population. METHODS: A literature search was performed using Cochrane Library, EMBASE, and Ovid MEDLINE databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A narrative review of papers discussing mechanisms of hypercoagulability in CS was conducted. RESULTS: Twenty-five relevant papers were identified out of 944 papers yielded. Pooled postoperative VTE incidence in patients undergoing transsphenoidal surgery for CD was 2% (58 out of 2997). The pooled rate of VTE-associated mortality based on the 23 studies that reported this information was 0.2% (6 out of 2077). There were no cases of postoperative VTE in the 191 patients undergoing adrenalectomy for benign adrenocorticotropic hormone-independent CS. Ten studies reported information on perioperative thromboprophylaxis strategies in transsphenoidal surgery for CD and adrenalectomy for adrenocorticotropic hormone-independent CS. CONCLUSIONS: Postoperative VTE in CD is a source of morbidity, with a rate of 2% and mortality rate of 0.2%, highlighting that surgical resection of the corticotroph adenoma does not necessarily result in immediate resolution of hypercoagulability. Increased production of coagulation factors, impaired fibrinolysis, inflammation, and CS-associated metabolic risk factors all factor into the pathogenesis of CS-associated hypercoagulability. Further study is needed on an optimal pharmacologic prophylaxis strategy.

The mitogenomic landscape of Banisteriopsis caapi (Malpighiaceae), the sacred liana used for ayahuasca preparation.

The sacred ayahuasca brew, utilized by indigenous communities in the Amazon and syncretic religious groups in Brazil, primarily consists of a decoction of two plants: (i) the Amazonian liana known as Mariri or Jagube (Banisteriopsis caapi), and (ii) the shrub referred as Chacrona or Rainha (Psychotria viridis). While Chacrona leaves are rich in N,N-Dimethyltryptamine (DMT), a potent psychedelic, the macerated vine of Mariri provides beta-carboline alkaloids acting as monoamine oxidase inhibitors, preventing DMT's degradation. This study sequenced, assembled, and analyzed the complete genome of B. caapi's mitochondrion, yielding a circular structure spanning 503,502 bp. Although the mtDNA encompasses most plant mitochondrial genes, it lacks some ribosomal genes, presents some atypical genes, and contains plastid pseudogenes, suggesting gene transfer between organelles. The presence of a 7-Kb repetitive segment containing copies of the rrnL and trnfM genes suggests mitogenome isomerization, supporting the hypothesis of dynamic mitogenome maintenance in plants. Phylogenetics and phylogenomics across 24 Malpighiales confirms the sample's placement in the "Tucunacá" ethnovariety, aligning with morphological identification. This study spearheads efforts to decode the genome of this esteemed Malpighiaceae.

Towards discovery: an end-to-end system for uncovering novel biomedical relations.

Biomedical relation extraction is an ongoing challenge within the natural language processing community. Its application is important for understanding scientific biomedical literature, with many use cases, such as drug discovery, precision medicine, disease diagnosis, treatment optimization and biomedical knowledge graph construction. Therefore, the development of a tool capable of effectively addressing this task holds the potential to improve knowledge discovery by automating the extraction of relations from research manuscripts. The first track in the BioCreative VIII competition extended the scope of this challenge by introducing the detection of novel relations within the literature. This paper describes that our participation system initially focused on jointly extracting and classifying novel relations between biomedical entities. We then describe our subsequent advancement to an end-to-end model. Specifically, we enhanced our initial system by incorporating it into a cascading pipeline that includes a tagger and linker module. This integration enables the comprehensive extraction of relations and classification of their novelty directly from raw text. Our experiments yielded promising results, and our tagger module managed to attain state-of-the-art named entity recognition performance, with a micro F1-score of 90.24, while our end-to-end system achieved a competitive novelty F1-score of 24.59. The code to run our system is publicly available at https://github.com/ieeta-pt/BioNExt. Database URL: https://github.com/ieeta-pt/BioNExt.

Development and initial validation of a data quality evaluation tool in obstetrics real-world data through HL7-FHIR interoperable Bayesian networks and expert rules.

Background: The increasing prevalence of electronic health records (EHRs) in healthcare systems globally has underscored the importance of data quality for clinical decision-making and research, particularly in obstetrics. High-quality data is vital for an accurate representation of patient populations and to avoid erroneous healthcare decisions. However, existing studies have highlighted significant challenges in EHR data quality, necessitating innovative tools and methodologies for effective data quality assessment and improvement. Objective: This article addresses the critical need for data quality evaluation in obstetrics by developing a novel tool. The tool utilizes Health Level 7 (HL7) Fast Healthcare Interoperable Resources (FHIR) standards in conjunction with Bayesian Networks and expert rules, offering a novel approach to assessing data quality in real-world obstetrics data. Methods: A harmonized framework focusing on completeness, plausibility, and conformance underpins our methodology. We employed Bayesian networks for advanced probabilistic modeling, integrated outlier detection methods, and a rule-based system grounded in domain-specific knowledge. The development and validation of the tool were based on obstetrics data from 9 Portuguese hospitals, spanning the years 2019-2020. Results: The developed tool demonstrated strong potential for identifying data quality issues in obstetrics EHRs. Bayesian networks used in the tool showed high performance for various features with area under the receiver operating characteristic curve (AUROC) between 75% and 97%. The tool's infrastructure and interoperable format as a FHIR Application Programming Interface (API) enables a possible deployment of a real-time data quality assessment in obstetrics settings. Our initial assessments show promised, even when compared with physicians' assessment of real records, the tool can reach AUROC of 88%, depending on the threshold defined. Discussion: Our results also show that obstetrics clinical records are difficult to assess in terms of quality and assessments like ours could benefit from more categorical approaches of ranking between bad and good quality. Conclusion: This study contributes significantly to the field of EHR data quality assessment, with a specific focus on obstetrics. The combination of HL7-FHIR interoperability, machine learning techniques, and expert knowledge presents a robust, adaptable solution to the challenges of healthcare data quality. Future research should explore tailored data quality evaluations for different healthcare contexts, as well as further validation of the tool capabilities, enhancing the tool's utility across diverse medical domains.

Solid-State NMR Characterization of Mefloquine Resinate Complexes Designed for Taste-Masking Pediatric Formulations.

Mefloquine (MQ) is an antimalarial medication prescribed to treat or malaria prevention.. When taken by children, vomiting usually occurs, and new doses of medication frequently need to be taken. So, developing pediatric medicines using taste-masked antimalarial drug complexes is mandatory for the success of mefloquine administration. The hypothesis that binding mefloquine to an ion-exchange resin (R) could circumvent the drug's bitter taste problem was proposed, and solid-state 13C cross-polarization magic angle spinning (CPMAS) NMR was able to follow MQ-R mixtures through chemical shift and relaxation measurements. The nature of MQ-R complex formation could then be determined. Impedimetric electronic tongue equipment also verified the resinate taste-masking efficiency in vitro. Variations in chemical shifts and structure dynamics measured by proton relaxation properties (e.g., T1ρH) were used as probes to follow the extension of mixing and specific interactions that would be present in MQ-R. A significant decrease in T1ρH values was observed for MQ carbons in MQ-R complexes, compared to the ones in MQ (from 100-200 ms in MQ to 20-50 ms in an MQ-R complex). The results evidenced that the cationic resin interacts strongly with mefloquine molecules in the formulation of a 1:1 ratio complex. Thus, 13C CPMAS NMR allowed the confirmation of the presence of a binding between mefloquine and polacrilin in the MQ-R formulation studied.

Multi-head CRF classifier for biomedical multi-class named entity recognition on Spanish clinical notes.

The identification of medical concepts from clinical narratives has a large interest in the biomedical scientific community due to its importance in treatment improvements or drug development research. Biomedical named entity recognition (NER) in clinical texts is crucial for automated information extraction, facilitating patient record analysis, drug development, and medical research. Traditional approaches often focus on single-class NER tasks, yet recent advancements emphasize the necessity of addressing multi-class scenarios, particularly in complex biomedical domains. This paper proposes a strategy to integrate a multi-head conditional random field (CRF) classifier for multi-class NER in Spanish clinical documents. Our methodology overcomes overlapping entity instances of different types, a common challenge in traditional NER methodologies, by using a multi-head CRF model. This architecture enhances computational efficiency and ensures scalability for multi-class NER tasks, maintaining high performance. By combining four diverse datasets, SympTEMIST, MedProcNER, DisTEMIST, and PharmaCoNER, we expand the scope of NER to encompass five classes: symptoms, procedures, diseases, chemicals, and proteins. To the best of our knowledge, these datasets combined create the largest Spanish multi-class dataset focusing on biomedical entity recognition and linking for clinical notes, which is important to train a biomedical model in Spanish. We also provide entity linking to the multi-lingual Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) vocabulary, with the eventual goal of performing biomedical relation extraction. Through experimentation and evaluation of Spanish clinical documents, our strategy provides competitive results against single-class NER models. For NER, our system achieves a combined micro-averaged F1-score of 78.73, with clinical mentions normalized to SNOMED CT with an end-to-end F1-score of 54.51. The code to run our system is publicly available at https://github.com/ieeta-pt/Multi-Head-CRF. Database URL: https://github.com/ieeta-pt/Multi-Head-CRF.

Assessment of High-fidelity Anatomical Models for Performing Pterional Approach: A Practical Clinic in American Association of Neurological Surgeons Meeting 2024.

BACKGROUND: Over the last decade, simulation models have been increasingly applied as an adjunct for surgical training in neurosurgery. We aim through a practical course at a national neurosurgical conference to evaluate 3D non-cadaveric simulation models along with augmented reality for learning and practicing the pterional craniotomy approach among a wide variety of participants including medical students, neurosurgery residents, and attending neurosurgeons. METHODS: Our course was conducted during an international neurosurgery meeting with 93 participants but the course surveys (pre- and post-course) were completed by 42 participants. RESULTS: Most participants were medical students (31; 73.8%). Participants with no experience (the majority) in cadaver lab dissections, craniotomy as first operator, and as second operator represented 12 (27.9%), 29 (69%), and 22 (52.4%), respectively. Participants with moderate experience in cadaver lab dissections were 23 (53.5%). Post-course survey respondents noted positive feedback in most items queried including enhancement of familiarity and acquiring skills, confidence with neurosurgery instruments, confidence with microscope, part of standard training, traditional training, and lifelong training. CONCLUSIONS: Simulation model combining augmented reality with physical simulation for hybrid experience can be a promising and valuable tool especially for medical students or early career neurosurgical residents.

Implementation of a Standardized Interdisciplinary Perioperative Protocol for Patients Undergoing Transsphenoidal Surgery: Impact on Patient Outcomes.

INTRODUCTION: Advances in endoscopic endonasal transsphenoidal surgery have led to improved postoperative outcomes after pituitary adenoma resection, including reduced length of stay, complications and readmission rates, without compromising safety and satisfaction. METHODS: Our team implemented a perioperative protocol in January 2021 for patients undergoing endoscopic, transsphenoidal pituitary surgery. This study compares preoperative characteristics and postoperative outcomes in 279 patients between 2016 and 2022 (128 preprotocol and 151 postprotocol). Our protocol includes interdisciplinary preoperative evaluations, unified communication, cortisol thresholds for postoperative glucocorticoid replacement, and fluid restriction to prevent delayed hyponatremia. RESULTS: Median age was 54 ± 17 years with 50.8% female patients. There were 229 (82.1%) macroadenomas (>1 cm) and 50 (17.9%) microadenomas/cysts (<1 cm). Mean diameter was 18 (transverse), 18 (craniocaudal), 16 (anteroposterior) mm. Tumor types included 125 (44.8%) gonadotroph, 46 (16.4%) adrenocorticotroph, 40 (14.3%) lactotroph, 26 (9.3%) Rathke cysts, 19 (6.8%) somatotroph, 13 (4.6%) nondiagnostic, 3 (1%) somatotroph-lactotroph, 3 (1%) mammosomatotroph, 2 (0.71%) null cell, and 2 (0.7%) thyrotroph adenomas. Postprotocol, 74.2% of patients were discharged on postoperative day 1 compared with 46.1% preprotocol (P < 0.0001). Transient arginine vasopressin deficiency decreased from 10.4% (preprotocol) to 4.6% postprotocol (P = 0.101). Hyponatremia occurred in 13.3% pre-protocol and 4.6% postprotocol. Emergency department visits dropped from 9.4% to 3.9%, and readmissions decreased from 7.8% to 2.6%. Persistent arginine vasopressin deficiency affected 2.3% preprotocol and 1.3% postprotocol patients. Cerebrospinal fluid leaks occurred in 8.5% preprotocol and 7.3% postprotocol. CONCLUSIONS: Implementing an interdisciplinary, perioperative protocol for transsphenoidal endoscopic pituitary surgery improves length of stay while minimizing readmissions and surgery-related complications.

Applications of the Methylotrophic Yeast Komagataella phaffii in the Context of Modern Biotechnology.

Komagataella phaffii (formerly Pichia pastoris) is a methylotrophic yeast widely used in laboratories around the world to produce recombinant proteins. Given its advantageous features, it has also gained much interest in the context of modern biotechnology. In this review, we present the utilization of K. phaffii as a platform to produce several products of economic interest such as biopharmaceuticals, renewable chemicals, fuels, biomaterials, and food/feed products. Finally, we present synthetic biology approaches currently used for strain engineering, aiming at the production of new bioproducts.

Genomic decoding of Theobroma grandiflorum (cupuassu) at chromosomal scale: evolutionary insights for horticultural innovation.

BACKGROUND: Theobroma grandiflorum (Malvaceae), known as cupuassu, is a tree indigenous to the Amazon basin, valued for its large fruits and seed pulp, contributing notably to the Amazonian bioeconomy. The seed pulp is utilized in desserts and beverages, and its seed butter is used in cosmetics. Here, we present the sequenced telomere-to-telomere genome of cupuassu, disclosing its genomic structure, evolutionary features, and phylogenetic relationships within the Malvaceae family. FINDINGS: The cupuassu genome spans 423 Mb, encodes 31,381 genes distributed in 10 chromosomes, and exhibits approximately 65% gene synteny with the Theobroma cacao genome, reflecting a conserved evolutionary history, albeit punctuated with unique genomic variations. The main changes are pronounced by bursts of long-terminal repeat retrotransposons at postspecies divergence, retrocopied and singleton genes, and gene families displaying distinctive patterns of expansion and contraction. Furthermore, positively selected genes are evident, particularly among retained and dispersed tandem and proximal duplicated genes associated with general fruit and seed traits and defense mechanisms, supporting the hypothesis of potential episodes of subfunctionalization and neofunctionalization following duplication, as well as impact from distinct domestication process. These genomic variations may underpin the differences observed in fruit and seed morphology, ripening, and disease resistance between cupuassu and the other Malvaceae species. CONCLUSIONS: The cupuassu genome offers a foundational resource for both breeding improvement and conservation biology, yielding insights into the evolution and diversity within the genus Theobroma.