The rise of taxon-specific epitope predictors.

Computational predictors of immunogenic peptides, or epitopes, are traditionally built based on data from a broad range of pathogens without consideration for taxonomic information. While this approach may be reasonable if one aims to develop one-size-fits-all models, it may be counterproductive if the proteins for which the model is expected to generalize are known to come from a specific subset of phylogenetically related pathogens. There is mounting evidence that, for these cases, taxon-specific models can outperform generalist ones, even when trained with substantially smaller amounts of data. In this comment, we provide some perspective on the current state of taxon-specific modelling for the prediction of linear B-cell epitopes, and the challenges faced when building and deploying these predictors.

Intraoperative use of processed electroencephalogram in a quaternary center: a quality improvement audit.

Although intraoperative electroencephalography (EEG) is not consensual among anesthesiologists, growing evidence supports its use to titrate anesthetic drugs, assess the level of arousal/consciousness, and detect ischemic cerebrovascular events; in addition, intraoperative EEG monitoring may decrease the incidence of postoperative neurocognitive disorders. Based on the known and potential benefits of intraoperative EEG monitoring, an educational program dedicated to staff anesthesiologists, residents of Anesthesiology and anesthesia technicians was started at Cleveland Clinic Abu Dhabi in May 2022 and completed in June 2022, aiming to have all patients undergoing general anesthesia with adequate brain monitoring and following international initiatives promoting perioperative brain health. All the surgical cases performed under General Anesthesia at 24 daily locations were prospectively inspected during 15 consecutive working days in March 2023. The use or absence of a processed EEG monitor was registered. Of 379 surgical cases distributed by 24 locations under General Anesthesia, 233 cases (61%) had processed EEG monitoring. The specialty with the highest use of EEG monitoring was Cardiothoracic Surgery, with 100% of cases, followed by interventional Cardiology (90%) and Vascular Surgery (75%). Otorhinolaryngology (29%), Gastrointestinal Endoscopy (25%), and Interventional Pulmonology (20%) were the areas with the lowest use of EEG monitoring. Of note, in the Neuroradiology suite, no processed EEG monitor was used in cases under General Anesthesia. We identified a reasonable use of EEG monitoring during general anesthesia, unfortunately not reaching our target of 100%. The educational and support program previously implemented within the Anesthesiology Institute needs to be continued and improved, including workshops, online discussions, and journal club sessions, to increase the use of EEG monitoring in underused areas.

Changes in motor evoked potentials after erector spinae block in scoliosis surgery-when to take pre-incision baseline recordings?

Multimodal intraoperative neurophysiological monitoring (IONM) is highly valuable in scoliosis surgeries for monitoring spinal cord function, particularly during instrumentation. Accurate timing of baseline recordings of TcMEP and SSEP is crucial, as any changes observed during surgery and instrumentation are compared to these baseline recordings. However, the impact of ultrasound-guided erector spinae block (USG-ESPB) on SSEP and TcMEP is not well-studied in scoliosis surgery. In this report, we present two cases of scoliosis surgery where bilateral two-level USG-ESPB using different concentrations of ropivacaine (0.375% and 0.2%) resulted in a transient and significant deterioration of TcMEP, occurring 3 minutes after the block and lasting for 20 minutes. Remarkably, SSEPs remained unchanged during this period. These findings suggest that USG-ESPB may produce TcMEP changes, highlighting the importance of carefully considering the timing of baseline TcMEP acquisition in scoliosis surgery.

Alternative sensor montage for Index based EEG monitoring. A systematic review.

The main objective of this systematic review is to assess the reliability of alternative positions of processed electroencephalogram sensors for depth of anesthesia monitoring and its applicability in clinical practice. A systematic search was conducted in PubMed, Embase, Cochrane Library, Clinical trial.gov in accordance with reporting guidelines of PRISMA statement together with the following sources: Google and Google Scholar. We considered eligible prospective studies, written in the English language. The last search was run on the August 2023. Risk of bias and quality assessment were performed. Data extraction was performed by two authors and results were synthesized narratively owing to the heterogeneity of the included studies. Thirteen prospective observational studies (438 patients) were included in the systematic review after the final assessment, with significant diversity in study design. Most studies had a low risk of bias but due to lack of information in one key domain of bias (Bias due to missing data) the overall judgement would be No Information. However, there is no clear indication that the studies are at serious or critical risk of bias. Bearing in mind, the heterogeneity and small sample size of the included studies, current evidence suggests that the alternative infraorbital sensor position is the most comparable for clinical use when the standard sensor position in the forehead is not possible.

Non-invasive technology for brain monitoring: definition and meaning of the principal parameters for the International PRactice On TEChnology neuro-moniToring group (I-PROTECT).

Technologies for monitoring organ function are rapidly advancing, aiding physicians in the care of patients in both operating rooms (ORs) and intensive care units (ICUs). Some of these emerging, minimally or non-invasive technologies focus on monitoring brain function and ensuring the integrity of its physiology. Generally, the central nervous system is the least monitored system compared to others, such as the respiratory, cardiovascular, and renal systems, even though it is a primary target in most therapeutic strategies. Frequently, the effects of sedatives, hypnotics, and analgesics are entirely unpredictable, especially in critically ill patients with multiple organ failure. This unpredictability exposes them to the risks of inadequate or excessive sedation/hypnosis, potentially leading to complications and long-term negative outcomes. The International PRactice On TEChnology neuro-moniToring group (I-PROTECT), comprised of experts from various fields of clinical neuromonitoring, presents this document with the aim of reviewing and standardizing the primary non-invasive tools for brain monitoring in anesthesia and intensive care practices. The focus is particularly on standardizing the nomenclature of different parameters generated by these tools. The document addresses processed electroencephalography, continuous/quantitative electroencephalography, brain oxygenation through near-infrared spectroscopy, transcranial Doppler, and automated pupillometry. The clinical utility of the key parameters available in each of these tools is summarized and explained. This comprehensive review was conducted by a panel of experts who deliberated on the included topics until a consensus was reached. Images and tables are utilized to clarify and enhance the understanding of the clinical significance of non-invasive neuromonitoring devices within these medical settings.

Electroencephalographic guided propofol-remifentanil TCI anesthesia with and without dexmedetomidine in a geriatric population: electroencephalographic signatures and clinical evaluation.

Elderly and multimorbid patients are at high risk for developing unfavorable postoperative neurocognitive outcomes; however, well-adjusted and EEG-guided anesthesia may help titrate anesthesia and improve postoperative outcomes. Over the last decade, dexmedetomidine has been increasingly used as an adjunct in the perioperative setting. Its synergistic effect with propofol decreases the dose of propofol needed to induce and maintain general anesthesia. In this pilot study, we evaluate two highly standardized anesthetic regimens for their potential to prevent burst suppression and postoperative neurocognitive dysfunction in a high-risk population. Prospective, randomized clinical trial with non-blinded intervention. Operating room and post anesthesia care unit at Hospital Base San José, Osorno/Universidad Austral, Valdivia, Chile. 23 patients with scheduled non-neurologic, non-cardiac surgeries with age > 69 years and a planned intervention time > 60 min. Patients were randomly assigned to receive either a propofol-remifentanil based anesthesia or an anesthetic regimen with dexmedetomidine-propofol-remifentanil. All patients underwent a slow titrated induction, followed by a target controlled infusion (TCI) of propofol and remifentanil (n = 10) or propofol, remifentanil and continuous dexmedetomidine infusion (n = 13). We compared the perioperative EEG signatures, drug-induced changes, and neurocognitive outcomes between two anesthetic regimens in geriatric patients. We conducted a pre- and postoperative Montreal Cognitive Assessment (MoCa) test and measured the level of alertness postoperatively using a sedation agitation scale to assess neurocognitive status. During slow induction, maintenance, and emergence, burst suppression was not observed in either group; however, EEG signatures differed significantly between the two groups. In general, EEG activity in the propofol group was dominated by faster rhythms than in the dexmedetomidine group. Time to responsiveness was not significantly different between the two groups (p = 0.352). Finally, no significant differences were found in postoperative cognitive outcomes evaluated by the MoCa test nor sedation agitation scale up to one hour after extubation. This pilot study demonstrates that the two proposed anesthetic regimens can be safely used to slowly induce anesthesia and avoid EEG burst suppression patterns. Despite the patients being elderly and at high risk, we did not observe postoperative neurocognitive deficits. The reduced alpha power in the dexmedetomidine-treated group was not associated with adverse neurocognitive outcomes.

Cross-species prediction of essential genes in insects.

MOTIVATION: Insects possess a vast phenotypic diversity and key ecological roles. Several insect species also have medical, agricultural and veterinary importance as parasites and disease vectors. Therefore, strategies to identify potential essential genes in insects may reduce the resources needed to find molecular players in central processes of insect biology. However, most predictors of essential genes in multicellular eukaryotes using machine learning rely on expensive and laborious experimental data to be used as gene features, such as gene expression profiles or protein-protein interactions, even though some of this information may not be available for the majority of insect species with genomic sequences available. RESULTS: Here, we present and validate a machine learning strategy to predict essential genes in insects using sequence-based intrinsic attributes (statistical and physicochemical data) together with the predictions of subcellular location and transcriptomic data, if available. We gathered information available in public databases describing essential and non-essential genes for Drosophila melanogaster (fruit fly, Diptera) and Tribolium castaneum (red flour beetle, Coleoptera). We proceeded by computing intrinsic and extrinsic attributes that were used to train statistical models in one species and tested by their capability of predicting essential genes in the other. Even models trained using only intrinsic attributes are capable of predicting genes in the other insect species, including the prediction of lineage-specific essential genes. Furthermore, the inclusion of RNA-Seq data is a major factor to increase classifier performance. AVAILABILITY AND IMPLEMENTATION: The code, data and final models produced in this study are freely available at https://github.com/g1o/GeneEssentiality/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Processed Electroencephalogram-Based Monitoring to Guide Sedation in Critically Ill Adult Patients: Recommendations from an International Expert Panel-Based Consensus.

BACKGROUND: The use of processed electroencephalography (pEEG) for depth of sedation (DOS) monitoring is increasing in anesthesia; however, how to use of this type of monitoring for critical care adult patients within the intensive care unit (ICU) remains unclear. METHODS: A multidisciplinary panel of international experts consisting of 21 clinicians involved in monitoring DOS in ICU patients was carefully selected on the basis of their expertise in neurocritical care and neuroanesthesiology. Panelists were assigned four domains (techniques for electroencephalography [EEG] monitoring, patient selection, use of the EEG monitors, competency, and training the principles of pEEG monitoring) from which a list of questions and statements was created to be addressed. A Delphi method based on iterative approach was used to produce the final statements. Statements were classified as highly appropriate or highly inappropriate (median rating ≥ 8), appropriate (median rating ≥ 7 but < 8), or uncertain (median rating < 7) and with a strong disagreement index (DI) (DI < 0.5) or weak DI (DI ≥ 0.5 but < 1) consensus. RESULTS: According to the statements evaluated by the panel, frontal pEEG (which includes a continuous colored density spectrogram) has been considered adequate to monitor the level of sedation (strong consensus), and it is recommended by the panel that all sedated patients (paralyzed or nonparalyzed) unfit for clinical evaluation would benefit from DOS monitoring (strong consensus) after a specific training program has been performed by the ICU staff. To cover the gap between knowledge/rational and routine application, some barriers must be broken, including lack of knowledge, validation for prolonged sedation, standardization between monitors based on different EEG analysis algorithms, and economic issues. CONCLUSIONS: Evidence on using DOS monitors in ICU is still scarce, and further research is required to better define the benefits of using pEEG. This consensus highlights that some critically ill patients may benefit from this type of neuromonitoring.

Peri-operative multimodal monitoring: a real need or a luxury?

The present case of a patient with several co-morbidities undergoing complex vitrectomy under peribulbar block and sedation with Target Controlled Infusion (TCI of propofol and dexmedetomidine with EEG and Analgesia Nociception Index (ANI) monitoring illustrates the benefits of multimodal monitoring to differentiate the effect of hypnotic and antinociceptive drugs.It is highlighted the delta-alpha electroencephalographic pattern showing adequate sedation, the beta arousal pattern in the EEG concommitant to decrease in the ANI translating insufficient anti-nociception.

Linear thinking does not reflect the newer 21st-century anesthesia concepts. A narrative review.

The brain constitutes a good example of a chaotic, nonlinear biological system where large neuronal networks operate chaotically with random connectivity. This critical state is significantly affected by the anesthetic loss of consciousness induced by drugs whose pharmacological behavior has been classically based on linear kinetics and dynamics. Recent developments in pharmacology and brain monitoring during anesthesia suggest a different view that we tried to explore in this article. The concepts of effect-site for hypnotic drugs modeling a maximum effect, electroencephalographic dynamics during induction, maintenance, and recovery from anesthesia are discussed, integrated into this alternative view, and how it may be applied in daily clinical practice.

The importance of monitoring cerebral oxygenation in non brain injured patients.

Over the past few years, the use of non-invasive neuromonitoring in non-brain injured patients has increased, as a result of the recognition that many of these patients are at risk of brain injury in a wide number of clinical scenarios and therefore may benefit from its application which allows interventions to prevent injury and improve outcome. Among these, are post cardiac arrest syndrome, sepsis, liver failure, acute respiratory failure, and the perioperative settings where in the absence of a primary brain injury, certain groups of patients have high risk of neurological complications. While there are many neuromonitoring modalities utilized in brain injured patients, the majority of those are either invasive such as intracranial pressure monitoring, require special skill such as transcranial Doppler ultrasonography, or intermittent such as pupillometry and therefore unable to provide continuous monitoring. Cerebral oximetry using Near infrared Spectroscopy, is a simple non invasive continuous measure of cerebral oxygenation that has been shown to be useful in preventing cerebral hypoxemia both within the intensive care unit and the perioperative settings. At present, current recommendations for standard monitoring during anesthesia or in the general intensive care concentrate mainly on hemodynamic and respiratory monitoring without specific indications regarding the brain, and in particular, brain oximetry. The aim of this manuscript is to provide an up-to-date overview of the pathophysiology and applications of cerebral oxygenation in non brain injured patients as part of non-invasive multimodal neuromonitoring in the early identification and treatment of neurological complications in this population.

Oxygen Reserve Index and Arterial Partial Pressure of Oxygen: Relationship in Open Heart Surgery.

BACKGROUND: Mild to moderate hyperoxia is potentially beneficial to patients undergoing open heart surgery. Oxygen Reserve Index (ORI) is a novel parameter that correlates to arterial oxygen tension (PaO2) in the hyperoxic range. This prospective study aimed to assess whether the relationship between ORI and PaO2 remains intact in the setting of open-heart surgery. METHODS: This study included patients undergoing valve, aortic arch and coronary artery bypass grafting (CABG) surgeries, on and off pump, between September 1st 2019 and August 31st 2021. Enrolled patients had arterial blood gas samples collected and analyzed after induction of anesthesia and increases in FiO2 in steps of 0.08 with ORI being recorded at the time of sample collection for cross reference and analysis. RESULTS: ORI values showed a statistically significant correlation with PaO2 values in the 100-200 mmHg range (r = 0.8193, p < 0.001). Additionally, there was a significant correlation between ORI and SpO2 values in the range of 95% and 100% (r = 0.529, p < 0.05). CONCLUSIONS: The preserved relationship between ORI and PaO2 in the mild and moderate hyperoxic range can allow more precise titration of oxygen therapy to guide therapy targeting normoxia, mildly and moderately hyperoxia. Additionally, it could have a potential use as an early warning system for impeding hypoxia.

Irreversible Geometrothermodynamics of Open Systems in Modified Gravity.

In this work, we explore the formalism of the irreversible thermodynamics of open systems and the possibility of gravitationally generated particle production in modified gravity. More specifically, we consider the scalar-tensor representation of f(R,T) gravity, in which the matter energy-momentum tensor is not conserved due to a nonminimal curvature-matter coupling. In the context of the irreversible thermodynamics of open systems, this non-conservation of the energy-momentum tensor can be interpreted as an irreversible flow of energy from the gravitational sector to the matter sector, which, in general, could result in particle creation. We obtain and discuss the expressions for the particle creation rate, the creation pressure, and the entropy and temperature evolutions. Applied together with the modified field equations of scalar-tensor f(R,T) gravity, the thermodynamics of open systems lead to a generalization of the ΛCDM cosmological paradigm, in which the particle creation rate and pressure are considered effectively as components of the cosmological fluid energy-momentum tensor. Thus, generally, modified theories of gravity in which these two quantities do not vanish provide a macroscopic phenomenological description of particle production in the cosmological fluid filling the Universe and also lead to the possibility of cosmological models that start from empty conditions and gradually build up matter and entropy.

Donor-derived acute myeloid leukemia in solid organ transplantation.

We report the transmission of acute myeloid leukemia (AML) undetected at donation from a deceased organ donor to two kidneys and one liver recipients. We reviewed the medical records, and performed molecular analyses and whole exome sequencing (WES) to ascertain AML donor origin and its molecular evolution. The liver recipient was diagnosed 11 months after transplantation and died from complications 2 months later. The two kidney recipients (R1 and R2) were diagnosed 19 and 20 months after transplantation and both received treatment for leukemia. R1 died of complications 11 months after diagnosis, while R2 went into complete remission for 44 months, before relapsing. R2 died 10 months later of complications from allogenic bone marrow transplantation. Microsatellite analysis demonstrated donor chimerism in circulating cells from both kidney recipients. Targeted molecular analyses and medical records revealed NPM1 mutation present in the donor and recipients, while FLT3 was mutated only in R1. These findings were confirmed by WES, which revealed additional founder and clonal mutations, and HLA genomic loss in R2. In conclusion, we report the first in-depth genomic analysis of AML transmission following solid organ transplantation, revealing distinct clonal evolution, and providing a potential molecular explanation for tumor escape.

Organism-specific training improves performance of linear B-cell epitope prediction.

MOTIVATION: In silico identification of linear B-cell epitopes represents an important step in the development of diagnostic tests and vaccine candidates, by providing potential high-probability targets for experimental investigation. Current predictive tools were developed under a generalist approach, training models with heterogeneous datasets to develop predictors that can be deployed for a wide variety of pathogens. However, continuous advances in processing power and the increasing amount of epitope data for a broad range of pathogens indicate that training organism or taxon-specific models may become a feasible alternative, with unexplored potential gains in predictive performance. RESULTS: This article shows how organism-specific training of epitope prediction models can yield substantial performance gains across several quality metrics when compared to models trained with heterogeneous and hybrid data, and with a variety of widely used predictors from the literature. These results suggest a promising alternative for the development of custom-tailored predictive models with high predictive power, which can be easily implemented and deployed for the investigation of specific pathogens. AVAILABILITY AND IMPLEMENTATION: The data underlying this article, as well as the full reproducibility scripts, are available at https://github.com/fcampelo/OrgSpec-paper. The R package that implements the organism-specific pipeline functions is available at https://github.com/fcampelo/epitopes. SUPPLEMENTARY INFORMATION: Supplementary materials are available at Bioinformatics online.

Salted or sweet? Hypertonic saline or mannitol for treatment of intracranial hypertension.

PURPOSE OF REVIEW: The aim of this review article is to present current recommendations regarding the use of hypertonic saline and mannitol for the treatment of intracranial hypertension. RECENT FINDINGS: In recent years, a significant number of studies have been published comparing hypertonic saline with mannitol in patients with acute increased intracranial pressure, mostly caused by traumatic brain injury. Albeit several randomized controlled trials, systematic reviews and meta-analysis support hypertonic saline as more effective than mannitol in reducing intracranial pressure, no clear benefit in regards to the long-term neurologic outcome of these patients has been reported. SUMMARY: Identifying and treating increased intracranial pressure is imperative in neurocritical care settings and proper management is essential to improve long-term outcomes. Currently, there is insufficient evidence from comparative studies to support a formal recommendation on the use of any specific hyperosmolar medication in patients with acute increased intracranial pressure.

Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass and fat mass indexes.

BACKGROUND/OBJECTIVES: Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely underrepresented in genomic studies. Here, we study the genetic architecture of BMI in children, young adults, and elderly individuals from the admixed population of Brazil. SUBJECTS/METHODS: Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European, and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of body mass index (BMI) in three Brazilian population-based cohorts from Northeast (Salvador), Southeast (Bambuí), and South (Pelotas). RESULTS: We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p = 2.76e-06). This variant is rare in Europeans but with frequencies of ~3% in West Africa and has a strong female-specific effect (95% CI: 2.32-5.65 kg/m2 per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from São Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains ~9% among women with morbid obesity from Pelotas, São Paulo, and Bambuí. The effect size of rs114066381 is at least five times higher than the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects. CONCLUSIONS: We identified six candidate SNPs associated with BMI. rs114066381 stands out for its high effect that was replicated and its high frequency in women with morbid obesity. We demonstrate how admixed populations are a source of new relevant phenotype-associated genetic variants.

Integrating microbial metagenomics and physicochemical parameters and a new perspective on starter culture for fine cocoa fermentation.

Cocoa beans used for chocolate production are fermented seeds of Theobroma cacao obtained by a natural fermentation process. The flavors and chemical compounds produced during the fermentation process make this step one of the most important in fine chocolate production. Herein, an integrative analysis of the variation of microbial community structure, using a shotgun metagenomics approach and associated physicochemical features, was performed during fermentation of fine cocoa beans. Samples of Forastero variety (FOR) and a mixture of two hybrids (PS1319 and CCN51) (MIX) from Bahia, Brazil, were analyzed at 7 different times. In the beginning (0 h), the structures of microbial communities were very different between FOR and MIX, reflecting the original plant-associated microbiomes. The highest change in microbial community structures occurred at the first 24 h of fermentation, with a marked increase in temperature and acetic acid concentration, and pH decrease. At 24-48 h both microbial community structures were quite homogenous regarding temperature, acetic acid, succinic acid, pH, soluble proteins and total phenols. During 72-96 h, the community structure resembles an acidic and warmer environment, prevailing few acetic acid bacteria. Taxonomic richness and abundance at 72-144 h exhibited significant correlation with temperature, reducing sugars, succinic, and acetic acids. Finally, we recommend that dominant microbial species of spontaneous fine cocoa fermentations should be considered as inoculum in accordance with the farm/region and GMP to maintain a differential organoleptic feature for production of fine chocolate. In our study, a starter inoculum composed of Acetobacter pausterianus and Hanseniaspora opuntiae strains is indicated.

Analgesia Nociception Index (ANI) and ephedrine: a dangerous liasion.

The Analgesia Nociception Index is a dimensionless scale derived from the heart rate variability; by analyzing the heart rate variability oscillations, it reflects the activity of the sympathetic and parasympathetic nervous systems and ultimately helps to evaluate the Nociception-Antinociception balance during anesthesia and surgery. Drugs like ephedrine affect the heart rate variability inducing artifacts in the ANI readings which should be taken into account in the clinical practice and in clinical research.

Loss of spectral alpha power during spine surgery: what could be wrong?

The electroencephalographic signatures of anesthetic drugs relate to a specific set of action mechanisms within the neural circuits. During intraoperative care, the recognition and correct interpretation of the EEG spectrogram can be used as a tool to guide anesthetic administration. For example, loss of alpha power during propofol anesthesia may be a sign of lighter level of hypnosis and/or of an increase in nociceptive inputs. We describe a case report of inadvertent interruption of propofol delivery that was first detected by changes in the electroencephalogram spectrogram.