Direct measurements of neurosteroid binding to specific sites on GABAA receptors.

BACKGROUND AND PURPOSE: Neurosteroids are allosteric modulators of GABAA currents, acting through several functional binding sites although their affinity and specificity for each site are unknown. The goal of this study was to measure steady-state binding affinities of various neurosteroids for specific sites on the GABAA receptor. EXPERIMENTAL APPROACH: Two methods were developed to measure neurosteroid binding affinity: (1) quenching of specific tryptophan residues in neurosteroid binding sites by the neurosteroid 17-methylketone group, and (2) FRET between MQ290 (an intrinsically fluorescent neurosteroid) and tryptophan residues in the binding sites. The assays were developed using ELIC-α1GABAAR, a chimeric receptor containing transmembrane domains of the α1-GABAA receptor. Tryptophan mutagenesis was used to identify specific interactions. KEY RESULTS: Allopregnanolone (3α-OH neurosteroid) was shown to bind at intersubunit and intrasubunit sites with equal affinity, whereas epi-allopregnanolone (3ß-OH neurosteroid) binds at the intrasubunit site. MQ290 formed a strong FRET pair with W246, acting as a site-specific probe for the intersubunit site. The affinity and site-specificity of several neurosteroid agonists and inverse agonists was measured using the MQ290 binding assay. The FRET assay distinguishes between competitive and allosteric inhibition of MQ290 binding and demonstrated an allosteric interaction between the two neurosteroid binding sites. CONCLUSIONS AND IMPLICATIONS: The affinity and specificity of neurosteroid binding to two sites in the ELIC-α1GABAAR were directly measured and an allosteric interaction between the sites was revealed. Adaptation of the MQ290 FRET assay to a plate-reader format will enable screening for high affinity agonists and antagonists for neurosteroid binding sites.

Transformation of Metal-Organic Framework from Kinetic to Thermodynamic Product for Controlled Delivery of Vitamin C.

A biocompatible metal-organic framework (MOF), named HSTC-4, constructed using the flexible 4,4'-oxybis(benzoic acid) (OBA), was developed to enable efficient loading and controlled release of vitamin C (VC) through a combination of strategies involving ligand length, structure design, and metal selection. The kinetic product HSTC-4 demonstrates a propensity for transforming into the thermodynamically stable HSTC-5 under external stimuli, such as photoillumination and vacuum heating, as witnessed by single-crystal to single-crystal transformation. Density functional theory (DFT) calculations reveal that the VC guest molecules exhibit stronger binding affinity with HSTC-5 due to its narrower pores compared to HSTC-4, resulting in a slower release of VC from VC@HSTC-5. Furthermore, precise control over VC release can be achieved by introducing surface modifications involving SiO2 onto the structure of VC@HSCT-5, while simultaneously adjusting environmental factors such as pH and temperature conditions. Preliminary cell culture experiments and cytotoxicity assays highlight the biocompatibility of HSTC-5, suggesting that it is a promising platform for sustained drug delivery and diverse biomedical applications.

The bioaccumulation and ecotoxicity of co-exposure of per(poly)fluoroalkyl substances and polystyrene microplastics to Eichhornia crassipes.

Gen X and F-53B have been popularized as alternatives to PFOA and PFOS, respectively. These per(poly)fluoroalkyl substances pervasively coexist with microplastics (MPs) in aquatic environments. However, there are knowledge gaps regarding their potential eco-environmental risks. In this study, a typical free-floating macrophyte, Eichhornia crassipes (E. crassipes), was selected for hydroponic simulation of a single exposure to PFOA, PFOS, Gen X, and F-53B, and co-exposure with polystyrene (PS) microspheres. F-53B exhibited the highest bioaccumulation followed by Gen X, PFOA, and PFOS. In the presence of PS MPs, the bioavailabilities of the four PFASs shifted and the whole plant bioconcentration factors improved. All four PFASs induced severe lipid peroxidation, which was exacerbated by PS MPs. The highest integrated biomarker response (IBR) was observed for E. crassipes (IBR of shoot: 30.01, IBR of root: 22.79, and IBR of whole plant: 34.96) co-exposed to PS MPs and F-53B. The effect addition index (EAI) model revealed that PS MPs showed antagonistic toxicity with PFOA and PFOS (EAI < 0) and synergistic toxicity with Gen X and F-53B (EAI > 0). These results are helpful to compare the eco-environmental impacts of legacy and alternative PFASs for renewal process of PFAS consumption and provide toxicological, botanical, and ecoengineering insights under co-contamination with MPs.

Fasudil alleviates alcohol-induced cognitive deficits and hippocampal morphology injury partly by altering the assembly of the actin cytoskeleton and microtubules.

Alcohol-Related Brain Damage (ARBD) manifests predominantly as cognitive impairment and brain atrophy with the hippocampus showing particular vulnerability. Fasudil, a Rho kinase (ROCK) inhibitor, has established neuroprotective properties; however, its impact on alcohol-induced cognitive dysfunction and hippocampal structural damage remains unelucidated. This study probes Fasudil's neuroprotective potential and identifies its mechanism of action in an in vivo context. Male C57BL/6 J mice were exposed to 30% (v/v, 6.0 g/kg) ethanol by intragastric administration for four weeks. Concurrently, these mice received a co-treatment with Fasudil through intraperitoneal injections at a dosage of 10 mg/kg/day. Fasudil was found to mitigate alcohol-induced spatial and recognition memory deficits, which were quantified using Y maze, Morris water maze, and novel object recognition tests. Concurrently, Fasudil attenuated hippocampal structural damage prompted by chronic alcohol exposure. Notably, Fasudil moderated alcohol-induced disassembly of the actin cytoskeleton and microtubules-mechanisms central to the maintenance of hippocampal synaptic integrity. Collectively, our findings indicate that Fasudil partially reverses alcohol-induced cognitive and morphological detriments by modulating cytoskeletal dynamics, offering insights into potential therapeutic strategies for ARBD.

[Pathogenesis and Targeted Treatment Progress of Splenomegaly in Primary Myelofibrosis--Review].

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm with splenomegaly as the major clinical manifestation, which is commonly considered to be linked to splenic extramedullary hematopoiesis. Alteration of CXCL12/CXCR4 pathway can lead to the migration of hematopoietic stem cells and hematopoietic progenitor cells from bone marrow to spleen which results in splenic extramedullary hematopoiesis. In addition, low GATA1 expression and the abnormal secretion of cytokines were found to be significantly associated with splenomegaly. With the application of JAK1/2 inhibitors in clinical, the symptoms of splenomegaly have been significantly improved in PMF patients. This article will review the pathogenesis and targeted treatment progress of splenomegaly in PMF.

Multi-Omics Characteristics of Ferroptosis Associated with Colon Adenocarcinoma Typing and Survival.

BACKGROUND: Ferroptosis, an iron-dependent form of cell death, plays a crucial role in the progression of various cancers, including colon adenocarcinoma (COAD). However, the multi-omics signatures relevant to ferroptosis regulation in COAD diagnosis remain to be elucidated. METHODS: The transcriptomic, miRNAomic, and methylomic profiles of COAD patients were acquired from the Cancer Genome Atlas (TCGA). Ferroptosis activity in these patients was determined, represented by a ferroptosis score (FS), using single-sample gene set enrichment analysis (ssGSEA) based on the expression of ferroptosis-related genes. RESULTS: Results showed that the COAD patients with high-FS displayed favorable survival outcomes and heightened drug sensitivity. They also exhibited an up-regulation of genes involved in immune-related pathways (e.g., tumor necrosis factor signaling pathway), suggesting a correlation between immunity and ferroptosis in COAD progression. Furthermore, three survival prediction models were established based on 10 CpGs, 12 long non-coding RNAs (lncRNAs), and 14 microRNAs (miRNAs), respectively. These models demonstrated high accuracy in predicting COAD survival, achieving areas under the curve (AUC) >0.7. The variables used in the three models also showed strong correlations at different omics levels and were effective at discriminating between high-FS and low-FS COAD patients (AUC >0.7). CONCLUSIONS: This study identified different DNA methylation (DNAm), lncRNA, and miRNA characteristics between COAD patients with high and low ferroptosis activity. Furthermore, ferroptosis-related multi-omics signatures were established for COAD prognosis and classification. These insights present new opportunities for improving the efficacy of COAD therapy.

[Metabolic mechanism and intervention strategy of atrial fibrillation in the elderly].

Atrial fibrillation (AF) is a cardiovascular epidemic that occurs primarily in the elderly with primary cardiovascular diseases, leading to severe consequences such as stroke and heart failure. The heart is an energy-consuming organ, which requires a high degree of metabolic flexibility to ensure a quick switch of metabolic substrates to meet its energy needs in response to physiological and pathological stimulation. Metabolism is closely related to the occurrence of AF, and AF patients manifest metabolic inflexibility, such as insulin resistance and the metabolic shift from aerobic metabolism to anaerobic glycolysis. Moreover, our research group and the others have shown that metabolic inflexibility is a crucial pathologic mechanism for AF. Energy metabolism is closely linked to the aging process and aging-related diseases, and impaired metabolic flexibility is considered as an essential driver of aging. Therefore, this review focuses on the alteration of metabolic flexibility in the elderly and reveals that impaired metabolic flexibility may be an important driver for the high prevalence of AF in the elderly, hoping to provide intervention strategies for the prevention and treatment of AF in the elderly.

The value of total tumor diameter in unilateral multifocal papillary thyroid carcinoma: a propensity score matching analysis.

Background: Tumor multifocality is frequently observed in papillary thyroid carcinoma (PTC). However, the maximum tumor diameter (MTD), currently utilized in various staging schemes, might not accurately indicate the level of aggressiveness exhibited by multifocal tumors. We aimed to investigate the relationship between total tumor diameter (TTD) and clinicopathological features of papillary thyroid carcinoma. Methods: Retrospective data analysis was done on 1936 individuals who underwent complete thyroidectomy for PTC. Patients were classified into subgroups according to unilateral multifocality, central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM). The relationships of clinicopathological features among these groups were analyzed. Results: Unilateral multifocality was observed in 117 patients. The clinicopathological features of the unilateral multifocal PTC were similar to the unifocal PTC with approximate TTD. The unilateral multifocality played no independent role in CLNM and LLNM. Moreover, the efficiency of TTD in predicting CLNM and LLNM was significantly higher than that of MTD. Conclusion: In the case of unilateral multifocal PTC, TTD is a more accurate indicator of the biological characteristics of the tumor than MTD.

Global development and future trends of artificial sweetener research based on bibliometrics.

Artificial sweeteners have sparked a heated debate worldwide due to their ambiguous impacts on public and environmental health and food safety and quality. Many studies on artificial sweeteners have been conducted; however, none scientometric studies exist in the field. This study aimed to elaborate on the knowledge creation and development of the field of artificial sweeteners and predict the frontiers of knowledge based on bibliometrics. In particular, this study combined VOSviewer, CiteSpace, and Bibliometrix to visualize the mapping of knowledge production, covered 2389 relevant scientific publications (1945-2022), and systematically analyzed articles and reviews (n = 2101). Scientific publications on artificial sweeteners have been growing at an annual rate of 6.28% and globally attracting 7979 contributors. Susan J. Brown with total publications (TP) of 17, average citation per article (AC) of 36.59, and Hirsch (h)-index of 12 and Robert F. Margolskee (TP = 12; AC = 2046; h-index = 11) were the most influential scholars. This field was clustered into four groups: eco-environment and toxicology, physicochemical mechanisms, public health and risks, and nutrition metabolism. The publications about environmental issues, in particular, "surface water," were most intensive during the last five years (2018-2022). Artificial sweeteners are gaining importance in the monitoring and assessment of environmental and public health. Results of the dual-map overlay showed that the future research frontiers tilt toward molecular biology, immunology, veterinary and animal sciences, and medicine. Findings of this study are conducive to identifying knowledge gaps and future research directions for scholars.

Telestration with augmented reality improves surgical performance through gaze guidance.

BACKGROUND: In minimally invasive surgery (MIS), trainees need to learn how to interpret the operative field displayed on the laparoscopic screen. Experts currently guide trainees mainly verbally during laparoscopic procedures. A newly developed telestration system with augmented reality (iSurgeon) allows the instructor to display hand gestures in real-time on the laparoscopic screen in augmented reality to provide visual expert guidance (telestration). This study analysed the effect of telestration guided instructions on gaze behaviour during MIS training. METHODS: In a randomized-controlled crossover study, 40 MIS naive medical students performed 8 laparoscopic tasks with telestration or with verbal instructions only. Pupil Core eye-tracking glasses were used to capture the instructor's and trainees' gazes. Gaze behaviour measures for tasks 1-7 were gaze latency, gaze convergence and collaborative gaze convergence. Performance measures included the number of errors in tasks 1-7 and trainee's ratings in structured and standardized performance scores in task 8 (ex vivo porcine laparoscopic cholecystectomy). RESULTS: There was a significant improvement 1-7 on gaze latency [F(1,39) = 762.5, p < 0.01, ηp2 = 0.95], gaze convergence [F(1,39) = 482.8, p < 0.01, ηp2 = 0.93] and collaborative gaze convergence [F(1,39) = 408.4, p < 0.01, ηp2 = 0.91] upon instruction with iSurgeon. The number of errors was significantly lower in tasks 1-7 (0.18 ± 0.56 vs. 1.94 ± 1.80, p < 0.01) and the score ratings for laparoscopic cholecystectomy were significantly higher with telestration (global OSATS: 29 ± 2.5 vs. 25 ± 5.5, p < 0.01; task-specific OSATS: 60 ± 3 vs. 50 ± 6, p < 0.01). CONCLUSIONS: Telestration with augmented reality successfully improved surgical performance. The trainee's gaze behaviour was improved by reducing the time from instruction to fixation on targets and leading to a higher convergence of the instructor's and the trainee's gazes. Also, the convergence of trainee's gaze and target areas increased with telestration. This confirms augmented reality-based telestration works by means of gaze guidance in MIS and could be used to improve training outcomes.

Changes in brain connectivity linked to multisensory processing of pain modulation in migraine with acupuncture treatment.

Migraine without aura (MWoA) is a major neurological disorder with unsatisfactory adherence to current medications. Acupuncture has emerged as a promising method for treating MWoA. However, the brain mechanism underlying acupuncture is yet unclear. The present study aimed to examine the effects of acupuncture in regulating brain connectivity of the key regions in pain modulation. In this study, MWoA patients were recruited and randomly assigned to 4 weeks of real or sham acupuncture. Resting-state functional magnetic resonance imaging (fMRI) data were collected before and after the treatment. A modern neuroimaging literature meta-analysis of 515 fMRI studies was conducted to identify pain modulation-related key regions as regions of interest (ROIs). Seed-to-voxel resting state-functional connectivity (rsFC) method and repeated-measures two-way analysis of variance were conducted to determine the interaction effects between the two groups and time (baseline and post-treatment). The changes in rsFC were evaluated between baseline and post-treatment in real and sham acupuncture groups, respectively. Clinical data at baseline and post-treatment were also recorded in order to determine between-group differences in clinical outcomes as well as correlations between rsFC changes and clinical effects. 40 subjects were involved in the final analysis. The current study demonstrated significant improvement in real acupuncture vs sham acupuncture on headache severity (monthly migraine days), headache impact (6-item Headache Impact Test), and health-related quality of life (Migraine-Specific Quality of Life Questionnaire). Five pain modulation-related key regions, including the right amygdala (AMYG), left insula (INS), left medial orbital superior frontal gyrus (PFCventmed), left middle occipital gyrus (MOG), and right middle cingulate cortex (MCC), were selected based on the meta-analysis on brain imaging studies. This study found that 1) after acupuncture treatment, migraine patients of the real acupuncture group showed significantly enhanced connectivity in the right AMYG/MCC-left MTG and the right MCC-right superior temporal gyrus (STG) compared to that of the sham acupuncture group; 2) negative correlations were established between clinical effects and increased rsFC in the right AMYG/MCC-left MTG; 3) baseline right AMYG-left MTG rsFC predicts monthly migraine days reduction after treatment. The current results suggested that acupuncture may concurrently regulate the rsFC of two pain modulation regions in the AMYG and MCC. MTG and STG may be the key nodes linked to multisensory processing of pain modulation in migraine with acupuncture treatment. These findings highlighted the potential of acupuncture for migraine management and the mechanisms underlying the modulation effects.

Advancing Prediction of Risk of Intraoperative Massive Blood Transfusion in Liver Transplantation With Machine Learning Models. A Multicenter Retrospective Study.

Background: Liver transplantation surgery is often accompanied by massive blood loss and massive transfusion (MT), while MT can cause many serious complications related to high mortality. Therefore, there is an urgent need for a model that can predict the demand for MT to reduce the waste of blood resources and improve the prognosis of patients. Objective: To develop a model for predicting intraoperative massive blood transfusion in liver transplantation surgery based on machine learning algorithms. Methods: A total of 1,239 patients who underwent liver transplantation surgery in three large grade lll-A general hospitals of China from March 2014 to November 2021 were included and analyzed. A total of 1193 cases were randomly divided into the training set (70%) and test set (30%), and 46 cases were prospectively collected as a validation set. The outcome of this study was an intraoperative massive blood transfusion. A total of 27 candidate risk factors were collected, and recursive feature elimination (RFE) was used to select key features based on the Categorical Boosting (CatBoost) model. A total of ten machine learning models were built, among which the three best performing models and the traditional logistic regression (LR) method were prospectively verified in the validation set. The Area Under the Receiver Operating Characteristic Curve (AUROC) was used for model performance evaluation. The Shapley additive explanation value was applied to explain the complex ensemble learning models. Results: Fifteen key variables were screened out, including age, weight, hemoglobin, platelets, white blood cells count, activated partial thromboplastin time, prothrombin time, thrombin time, direct bilirubin, aspartate aminotransferase, total protein, albumin, globulin, creatinine, urea. Among all algorithms, the predictive performance of the CatBoost model (AUROC: 0.810) was the best. In the prospective validation cohort, LR performed far less well than other algorithms. Conclusion: A prediction model for massive blood transfusion in liver transplantation surgery was successfully established based on the CatBoost algorithm, and a certain degree of generalization verification is carried out in the validation set. The model may be superior to the traditional LR model and other algorithms, and it can more accurately predict the risk of massive blood transfusions and guide clinical decision-making.

The Effect of Trustor Age and Trustee Age on Trustworthiness Judgments: An Event-Related Potential Study.

Perceived trustworthiness based on facial appearance plays an important role in interpersonal trust and cooperative behavior. Interpersonal trust behaviors involve both trustors and trustees. However, there is no clear conclusion on how the age of the two individuals affects interpersonal trust behaviors. Therefore, this study used the trust game task to explore the differences in trust behaviors between two different age groups in response to faces of different ages and analyzed whether such differences were apparent in the face processing stage. The behavioral results showed that only younger adults invested more money with older partners than younger ones; that is, younger adults trusted older faces more. The event-related potential (ERP) analyses showed that in the early stage of face processing, younger faces elicited more negative N170 than older faces; at the same time, older faces elicited more positive VPP than younger faces, and younger adults had more positive VPP than older adults. In the middle and late stages of face processing, younger faces elicited more negative FRN than older faces in younger adults but not in older adults. In addition, older faces elicited more positive LPP than younger faces in older adults but not in younger adults. The neural analyses suggested that age-related differences in facial trustworthiness judgments might occur in the later stages of face processing. Combining the behavioral and neural results, we found a dissociation between trustworthiness perceptions and trust behaviors in both younger and older adults, which may provide insight into how to prevent older adults from being deceived.

Response to Brigatinib Targeted Therapy in Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon 19 Deletion, T790M, and cis-C797S Triple Mutations: A Case Report.

Epidermal growth factor receptor (EGFR) triple mutations with exon 19 deletion (del19), T790M, and cis-C797S (del19/T790M/cis-C797S mutations) frequently occur in patients with non-small cell lung cancer (NSCLC), while progression to frontline EGFR-tyrosine kinase inhibitors (TKIs) and osimertinib was resistant to all clinically available EGFR-TKIs. Brigatinib monotherapy may be a potential treatment for NSCLC harboring del19/T790M/cis-C797S mutations based on preclinical studies; however, no clinical report has evaluated its efficacy on EGFR del19/T790M/cis-C797S mutations. Herein, we present a case of a female patient with EGFR del19-mutated NSCLC treated with afatinib followed by osimertinib due to acquired T790M mutation. The EGFR del19/T790M/cis-C797S mutations were detected following osimertinib treatment. Complete response of skull metastasis was confirmed after brigatinib treatment (90 mg daily). Unfortunately, she experienced intolerable adverse events; therefore, brigatinib was discontinued after three-month usage. This report provides the first reported evidence for the use of brigatinib monotherapy in patients with NSCLC harboring EGFR del19/T790M/cis-C797S mutations after progression to previous EGFR-TKIs.

Rapid Internal Control Reference Recombinase-Aided Amplification Assays for EBV and CMV Detection.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV), two of the most prevalent human herpesviruses, cause a wide spectrum of diseases and symptoms and are associated with serious health problem. In this study, we developed an internal control reference recombinase-aided amplification (ICR-RAA) assay for the rapid detection of EBV and CMV within 30 min. The assay had a sensitivity of 5 and 1 copies/test for EBV and CMV, respectively, with no cross reaction with other pathogens. In comparison with those of the commercial quantitative polymerase chain reaction (qPCR), the sensitivity of the EBV and CMV ICR-RAAs using extracted DNA was 93.33% and 84.84%, respectively; the specificity was 98.75% and 100.00%, respectively; and the Kappa values were 0.930 and 0.892 ( P < 0.05), respectively. In comparison with those of qPCR, the sensitivity of the EBV and CMV ICR-RAAs using the DNA by thermal lysis was 72.22% and 80.00%, respectively; the specificity was 100.00%; and the Kappa values were 0.764 and 0.878 ( P < 0. 05), respectively. Thus, rapid and specific detection of EBV and CMV is possible using ICR-RAA assays.

Validation of Trifluoromethylphenyl Diazirine Cholesterol Analogues As Cholesterol Mimetics and Photolabeling Reagents.

Aliphatic diazirine analogues of cholesterol have been used previously to elaborate the cholesterol proteome and identify cholesterol binding sites on proteins. Cholesterol analogues containing the trifluoromethylphenyl diazirine (TPD) group have not been reported. Both classes of diazirines have been prepared for neurosteroid photolabeling studies and their combined use provided information that was not obtainable with either diazirine class alone. Hence, we prepared cholesterol TPD analogues and used them along with previously reported aliphatic diazirine analogues as photoaffinity labeling reagents to obtain additional information on the cholesterol binding sites of the pentameric Gloeobacter ligand-gated ion channel (GLIC). We first validated the TPD analogues as cholesterol substitutes and compared their actions with those of previously reported aliphatic diazirines in cell culture assays. All the probes bound to the same cholesterol binding site on GLIC but with differences in photolabeling efficiencies and residues identified. Photolabeling of mammalian (HEK) cell membranes demonstrated differences in the pattern of proteins labeled by the two classes of probes. Collectively, these date indicate that cholesterol photoaffinity labeling reagents containing an aliphatic diazirine or TPD group provide complementary information and will both be useful tools in future studies of cholesterol biology.

A sex-linked SNP mutation in amhr2 is responsible for male differentiation in obscure puffer (Takifugu obscurus).

BACKGROUND: Anti-Mullerian hormone receptor type II (Amhr2) is a key receptor of Amh signaling in regulating gonad development. The amhr2 gene has been identified in numerous species, including a few teleost fishes. However, the roles of Amhr2 in Amh signaling in fish are poorly studied. METHODS AND RESULTS: In this study, an amhr2 homolog from obscure puffer (Takifugu obscurus) was identified, and its molecular characteristics were systematically analyzed. Expression analysis revealed that amhr2 was highly expressed in the gonads of adult pufferfish and significantly upregulated during sex differentiation. Significantly, a sex-linked SNP site was verified in obscure puffer amhr2. Females exhibited a homozygous genotype (C/C), while males possessed a heterozygous genotype (C/G), resulting in an amino acid variation (His/Asp384) in the kinase domain of Amhr2. Then, the functions of the different Amhr2 genotypes were further investigated. The male genotype protein (Amhr2D384) showed an enhanced ability to interact with the type I receptor (Bmpr1a) compared to the female genotype (Amhr2H384). The phosphorylation levels of Smads and activity of the target gene (id3) induced by the male genotype were also much higher than those induced by the female genotype. These results confirmed that the male genotype had an enhanced effect on the Amh signaling pathway compared with the female genotype. CONCLUSIONS: This study provides direct experimental evidence for the roles of different Amhr2 genotypes in pufferfish and suggests that amhr2 is responsible for male sex differentiation in obscure puffer.

Machine Learning for the Prediction of Red Blood Cell Transfusion in Patients During or After Liver Transplantation Surgery.

Aim: This study aimed to use machine learning algorithms to identify critical preoperative variables and predict the red blood cell (RBC) transfusion during or after liver transplantation surgery. Study Design and Methods: A total of 1,193 patients undergoing liver transplantation in three large tertiary hospitals in China were examined. Twenty-four preoperative variables were collected, including essential population characteristics, diagnosis, symptoms, and laboratory parameters. The cohort was randomly split into a train set (70%) and a validation set (30%). The Recursive Feature Elimination and eXtreme Gradient Boosting algorithms (XGBOOST) were used to select variables and build machine learning prediction models, respectively. Besides, seven other machine learning models and logistic regression were developed. The area under the receiver operating characteristic (AUROC) was used to compare the prediction performance of different models. The SHapley Additive exPlanations package was applied to interpret the XGBOOST model. Data from 31 patients at one of the hospitals were prospectively collected for model validation. Results: In this study, 72.1% of patients in the training set and 73.2% in the validation set underwent RBC transfusion during or after the surgery. Nine vital preoperative variables were finally selected, including the presence of portal hypertension, age, hemoglobin, diagnosis, direct bilirubin, activated partial thromboplastin time, globulin, aspartate aminotransferase, and alanine aminotransferase. The XGBOOST model presented significantly better predictive performance (AUROC: 0.813) than other models and also performed well in the prospective dataset (accuracy: 76.9%). Discussion: A model for predicting RBC transfusion during or after liver transplantation was successfully developed using a machine learning algorithm based on nine preoperative variables, which could guide high-risk patients to take appropriate preventive measures.