Individual Sequences Research Articles

Whole-body PET/MRI to detect bone metastases: comparison of the diagnostic performance of the sequences.

Whole-body positron emission tomography/magnetic resonance imaging (WB-PET/MRI) is increasingly used in the initial evaluation of oncology patients. The purpose of this study was to compare the diagnostic performance of WB MRI sequences, attenuation-corrected raw data positron-emission tomography (AC PET), and PET/MRI fused images to detect bone metastases. We included 765 consecutive oncologic patients who received WB-PET/MRI from between January 2017 and September 2023. The presence of bone metastases was assessed using the individual sequences by two radiologists. Interobserver agreement was calculated. A receiver operating characteristic (ROC) analysis was performed to assess the performance of each individual sequence and fused images. Interobserver agreement for the detection of bone metastases on all sequences ranged from good to very good. The reading of the combination of MRI sequences with PET images showed statistically significantly better performance than the reading of individual MRI sequences and PET component only. Contrast enhanced T1 W Volume-interpolated breath-hold examination (CE T1W VIBE) sequence superior to PET for the detection of bone metastasis, but the statistical significance was not as high as with T1W-PET and CE T1W-PET fused images. The highest performance was achieved by the fused CE T1W-PET images with sensitivity of 100%, specificity of 92%, PPV of 96%, and NPV of 100%. The combination of these CE T1W VIBE sequences with PET images have the highest diagnostic performance in detecting bone metastases in oncologic patients. This sequence should be integrated in WB-PET/MRI acquisitions for initial staging of cancer.

PI-QUAL version 2 image quality categorisation and inter-reader agreement compared to version 1.

Prostate imaging quality (PI-QUAL) was developed to standardise the evaluation of prostate MRI quality and has recently been updated to version 2. This study aims to assess inter-reader agreement for PI-QUAL v1 and v2 scores and investigates changes in MRI quality score categories. The study retrospectively analysed 350 multiparametric MRI (mpMRI) scans. Two expert uroradiologists independently assessed mpMRI quality using PI-QUAL v1 and v2 guidelines. Biparametric MRI (bpMRI) categorisation based on PI-QUAL v2 included only T2WI and diffusion-weighted imaging (DWI) results. Inter-reader agreement was determined using percentage agreement and kappa, and categorisation comparisons were made using the chi-square test. Substantial inter-reader agreement was observed for the overall PI-QUAL v1 score (κ = 0.64) and moderate agreement for v2 mpMRI (κ = 0.54) and v2 bpMRI scores (κ = 0.57). Inter-reader agreements on individual sequences were similar between v1 and v2 (kappa for individual sequences: T2WI, 0.46 and 0.49; DWI, 0.66 and 0.70; DCE, 0.71 and 0.61). Quality levels shifted from predominantly "optimal" in v1 (65%) down to "acceptable" using v2 (55%); p < 0.001. The addition of DCE increased the proportion of cases with at least "adequate" quality at mpMRI (64%) compared to bpMRI (30%); p < 0.001. This study shows consistent inter-reader agreement between PI-QUAL v1 and v2, encompassing overall and individual sequence categorisation. A notable shift from "optimal" to "acceptable" quality was demonstrated when moving from v1 to v2, with DCE tending improving quality from "inadequate" (bpMRI) to "acceptable" (mpMRI). Question What are the agreement levels of image quality of prostate MRI by using PI-QUAL v1 and v2? Findings Inter-reader agreement based on PI-QUAL v1 and v2 is comparable. Dynamic contrast enhancement (DCE) enables an overall shift from inadequate quality (at bpMRI) to acceptable quality (mpMRI). Clinical relevance The inter-reader agreement on PI-QUAL v1 and v2 is equivalent. PI-QUAL v2 assesses prostate bpMRI as well as mpMRI quality. Transitioning from inadequate to acceptable between v2-bpMRI and v2-mpMRI highlights the role of DCE as an "image quality safety net."

Hydrogel-Based Microdroplet Ensembles Encapsulating Multiplexed EXPAR Assays for Trichromic Digital Profiling of MicroRNAs and in-Depth Classification of Primary Urethral Cancers.

The primary challenge in microarray-based biological analysis lies in achieving the sensitive and specific detection of single-molecule targets while ensuring high reproducibility. A user-friendly digital imaging platform has been developed for the encoded trichromic profiling of circulating microRNAs (miRNAs). This platform replaces the traditional exponential polymerase amplification reaction (EXPAR) conducted on the microliter scale with a system that confines the amplification process within thousands of femtoliter-sized microdroplet reactors, cross-linked from tetra-armed poly(ethylene glycol) acrylate (Tetra-PEGA) and poly(ethylene glycol) dithiol (HS-PEG-SH), thus offering significant advantages, including minimal sample input, enhanced reactivity, and simplified analytical procedures. The quantitative analysis relies on digital counting of fluorescently positive microdroplets, each containing an individual miRNA sequence. This approach significantly reduces nonspecific amplification and improves sensitivity by over 2 orders of magnitude. The system has shown great potential in differentiating between subtypes of primary urethral carcinoma, suggesting its practical application in routine cancer diagnostics through simple urinalysis.

De novo genetic variant in epileptic encephalopathy: Importance of specific diagnosis

Introduction: Early infantile epileptic encephalopathies (EIEE) are rare syndromes that affect neurological development. The etiology has been uncertain for a long time, but advances in genetics have identified numerous associated genes. Variants in the CYFIP2 gene have been linked to EIEE. Clinical case: An 11-year-old female born at term without complications, with microcephaly, synophrys, and short neck. No relevant family history. At one month, she developed generalized seizures and delayed neurodevelopment, progressing to severe spastic quadriparesis, requiring gastrostomy and tracheostomy, with paroxysmal discharges on electroencephalogram. She received multiple anticonvulsant medications and ketogenic therapy. Complete individual exome sequencing and analysis of deletions and duplications were requested. Individual complete exome + deletions and duplications analysis (CNV) identified a probably pathogenic heterozygous variant in the CYFIP2 gene variant c.259C&gt;T (p.Arg87Cys) missense type, allelic ratio (VAF) 0.45. The results of this molecular study support the diagnosis of developmental and epileptic encephalopathy de novo. Discussion: Developmental and epileptic encephalopathy (EED) disorders are severe conditions that begin in childhood, characterized by epileptic seizures, abnormalities in the electroencephalogram, and deterioration of neurodevelopment. Genetic EEDs are associated with variants in various genes related to cellular and neuronal functions. The CYFIP2 gene, on chromosome 5q33.3, encodes protein 2 that interacts with FMRP (fragile X mental retardation protein), playing a crucial role in neurological development. De novo variants, such as nonsense mutations and truncation in CYFIP2, are associated with intellectual disability, seizures, and muscle hypotonia. Advancements in genomics are improving the understanding of epilepsy, impacting targeted treatment, prognosis, and patient counseling. Childhood epilepsy has a heterogeneous genetic basis, and some patients without previous diagnosis can now receive one, crucial for the implementation of precision medicine.

Private detection of relatives in forensic genomics using homomorphic encryption.

Forensic analysis heavily relies on DNA analysis techniques, notably autosomal Single Nucleotide Polymorphisms (SNPs), to expedite the identification of unknown suspects through genomic database searches. However, the uniqueness of an individual's genome sequence designates it as Personal Identifiable Information (PII), subjecting it to stringent privacy regulations that can impede data access and analysis, as well as restrict the parties allowed to handle the data. Homomorphic Encryption (HE) emerges as a promising solution, enabling the execution of complex functions on encrypted data without the need for decryption. HE not only permits the processing of PII as soon as it is collected and encrypted, such as at a crime scene, but also expands the potential for data processing by multiple entities and artificial intelligence services. This study introduces HE-based privacy-preserving methods for SNP DNA analysis, offering a means to compute kinship scores for a set of genome queries while meticulously preserving data privacy. We present three distinct approaches, including one unsupervised and two supervised methods, all of which demonstrated exceptional performance in the iDASH 2023 Track 1 competition. Our HE-based methods can rapidly predict 400 kinship scores from an encrypted database containing 2000 entries within seconds, capitalizing on advanced technologies like Intel AVX vector extensions, Intel HEXL, and Microsoft SEAL HE libraries. Crucially, all three methods achieve remarkable accuracy levels (ranging from 96% to 100%), as evaluated by the auROC score metric, while maintaining robust 128-bit security. These findings underscore the transformative potential of HE in both safeguarding genomic data privacy and streamlining precise DNA analysis. Results demonstrate that HE-based solutions can be computationally practical to protect genomic privacy during screening of candidate matches for further genealogy analysis in Forensic Genetic Genealogy (FGG).

Structural variation in the pangenome of wild and domesticated barley.

Pangenomes are collections of annotated genome sequences of multiple individuals of a species1. The structural variants uncovered by these datasets are a major asset to genetic analysis in crop plants2. Here we report a pangenome of barley comprising long-read sequence assemblies of 76 wild and domesticated genomes and short-read sequence data of 1,315 genotypes. An expanded catalogue of sequence variation in the crop includes structurally complex loci that are rich in gene copy number variation. To demonstrate the utility of the pangenome, we focus on four loci involved in disease resistance, plant architecture, nutrient release and trichome development. Novel allelic variation at a powdery mildew resistance locus and population-specific copy number gains in a regulator of vegetative branching were found. Expansion of a family of starch-cleaving enzymes in elite malting barleys was linked to shifts in enzymatic activity in micro-malting trials. Deletion of an enhancer motif is likely to change the developmental trajectory of the hairy appendages on barley grains. Our findings indicate that allelic diversity at structurally complex loci may have helped crop plantsto adapt to new selective regimes in agricultural ecosystems.

Semi-constant source radius and variable stress drop of repeating earthquakes: A fluid-invasion hypothesis for earthquake generation

Summary Earthquakes with very similar waveforms have been recognized as repeating earthquakes, or repeaters, which are interpreted as repeated ruptures of an isolated, frictionally locked asperity patch that are caused by stress loading due to aseismic slip in the surrounding stable regime of the fault. Ideally, the repeated ruptures of the same asperity result in the same source dimension and stress drop. However, significant variations in the stress drop have been observed during fluid-injection experiments even for a single repeater sequence. This study focuses repeater sequences in three different tectonic regimes beneath the Japanese Islands and investigates variations in the source dimension and stress drop in the same repeater sequences. The obtained results show that the variation in the source radius is mostly within 20–30% in individual repeater sequences but the stress drop is largely variable by one order of magnitude or more. We propose a fluid-invasion hypothesis to explain our observations. When pore-fluid pressures gradually invade into an asperity, the edge of the asperity tends to behave as aseismic because of the reduction of the effective normal stress to values below the critical value of effective normal stress, which makes the source radius somewhat smaller. Simultaneously, the amount of the fluid invasion into the asperity fluctuates the shear strength of the asperity, with the stress drop being smaller for higher pore-fluid pressures. The reduced source radius and stress drop expected from the fluid-invasion hypothesis can explain positive correlations between the source radius and seismic moment. We propose a conceptual model for earthquake generation by involving the triggering of aseismic slip by the enhancement of pore-fluid pressures and subsequent rupture of asperity by the stress loading due to the aseismic slip, which can be potentially applied to the genesis of repeaters and non-repeaters.

INNV-19. MULTIMODAL THERAPY FOR BRAF V600E MUTANT MELANOMA BRAIN METASTASES: CHARACTERIZATION OF CHRONOLOGICAL TREATMENT STRATEGIES AND ASSOCIATIONS WITH OVERALL SURVIVAL

Abstract BACKGROUND B-raf proto-oncogene (BRAF)-mutant melanoma brain metastases (BRAF MBM) are associated with poor prognosis. Amidst our large institutional experience treating patients with BRAF MBM with multimodality therapy, our aim was to identify disease and treatment-related prognostic features, accounting for longitudinal sequence of events, to inform clinical decision-making. METHODS We retrospectively reviewed electronic health records of 100 patients with primary cutaneous melanoma diagnosed with BRAF MBM. Demographic, disease, and clinical factors including treatment sequencing were tabulated. Descriptive statistics were used to summarize the study population and non-parametric tests were used to evaluate differences across groups. A multivariable Cox regression identified factors associated with overall survival (OS) following BRAF MBM diagnosis. RESULTS Median follow-up was 22 months and median OS was 33.5 months. Patients received an average [standard deviation (SD)] of 3.36 [1.06] unique therapies. After adjustment for covariates, greater number of brain metastases at initial diagnosis (hazard ratio (HR) 2.3 [1.14-4.62], p=0.01 for 3-10 metastases and HR 2.54 [1.01-6.36], p=0.04 for &amp;gt;10 metastases, respectively), receipt of combination IO and targeted therapy prior to BRAF MBM diagnosis (HR 2.91 [1.08-7.86], p=0.03), and receipt of no unique subsequent therapy after initial management strategy (HR 3.89 [1.48-10.16], p=0.005) were significantly associated with worse OS. CONCLUSIONS Despite heterogeneity in individual treatment sequences, patients with greater intracranial disease burden and those receiving combination targeted and immunotherapy prior to BRAF MBM diagnoses had the worst outcomes. Dynamic changes in therapy resistance may inform optimal treatment strategies for individuals with BRAF MBM.

Metal-antimicrobial peptides combo: promising weapons to combat bacteria invaders

Antimicrobial resistance has significantly increased over the last 30 years, prompting scientists to continuously look for novel, effective ways to combat drug-resistant bacteria and fungi. Due to their broad range of effectiveness, ease of synthesis, and ability to avoid resistance, antimicrobial peptides (AMPs) represent a potential approach. The direct investigation of metal effects on peptide activity has not received much attention. Divalent metal ions such as Zn(II), Cu(II), Ni(II), and Fe(II) do, in fact, influence some AMPs, producing an effect on their mode of action or function. Although the precise process by which metals are involved in microbial death is not well understood, this review goes into detail on several potential strategies to enhance AMPs activity through the synergy with metals. Important variables in these interactions include the individual peptide sequence, the type of metal ion, the capacity of metal to form chelates, and the softness of the ligand/metal complex. This article offers a thorough summary of the ways in which metal ions alter the structure of AMPs to boost their activity or sequester metal to impact on bacteria function.

Travel pattern recognition of urban rail passengers based on spatiotemporal sequence similarity

Understanding passenger travel patterns is helpful for the allocation of passenger resources in urban rail transit. Based on rail transit smart card data, this paper proposes a method to identify travel patterns by modeling individual spatiotemporal sequences. First, all the stations visited by individual passengers are extracted, and the similarity of the stations is calculated by the frequency of inter-station travel, the distance between stations and the activity duration of the stations. The main spatial activity area of the individual is divided using a hierarchical clustering algorithm. Then, the spatiotemporal sequence is inferred based on the individual's travel order. The sequence is a set of discrete values that characterize the spatiotemporal state. PCA-KL and K-Means++ are used to extract the similarity sequence structure to identify the passenger travel pattern. Finally, the rail transit smart card data of Xi'an in a certain month is taken as an example to identify its passenger travel pattern. The results show that complex passenger flow has 5 travel modes, of which 3 typical modes are commuting travel in a macro sense, accounting for 79% of the passenger flow. It can be seen that the pattern recognition based on the similarity of individual spatiotemporal sequences in this paper fully reflects the particularity and versatility of the research method, and is highly operational for different cities.

Three new species of Talaromyces sect. Talaromyces discovered in China.

Talaromyces species play an important role in the nutrient cycle in natural ecosystems, degradation of vegetal biomass in industries and the implications in medicine. However, the species diversity of this genus is still far from fully understood. The polyphasic taxonomic approach integrating morphological comparisons and molecular phylogenetic analyses based on BenA, CaM, Rpb2 and ITS sequences was used to propose three new Talaromyces species. Three new species of sect. Talaromyces isolated from soil are proposed, namely, T. disparis (ex-type AS3.26221), T. funiformis (ex-type AS3.26220) and T. jianfengicus (ex-type AS3.26253). T. disparis is unique in low growth rate, velvety texture, limited to moderate sporulation, biverticillate, monoverticillate and irregular penicilli bearing a portion of abnormally large globose conidia, it has no close relatives in phylogeny. Being a member of T. pinophilus complex, T. funiformis produces mycelial funicles on Czapek yeast autolysate agar (CYA), 5% malt extract agar (MEA) and yeast extract (YES), sparse sporulation on Czapek agar (Cz), CYA, MEA and YES while abundant on oatmeal agar (OA), bearing appressed biverticillate penicilli and globose to pyriform conida with smooth to finely rough walls. T. jianfengicus belongs to T. verruculosus complex, is characterized by velvety colony texture with moderate to abundant elm-green conidia en masse, producing biverticillate penicilli, globose conidia with verrucose walls. It is now a common practice in establishing new species of Aspergillus, Penicillium and Talaromyces based on morphological characters and phylogenetic analyses of BenA, CaM, Rpb2 and ITS sequences. The proposal of the three novelties of Talaromyces in this article is not only supported by their morphological distinctiveness, but also confirmed by the phylogenetic analyses of the concatenated BenA-CaM-Rpb2 and BenA-CaM-ITS, as well as the individual BenA, CaM, Rpb2 and ITS sequence matrices.

Differences in HIV-1 reservoir size, landscape characteristics and decay dynamics in acute and chronic treated HIV-1 Clade C infection.

Persisting HIV reservoir viruses in resting CD4 T cells and other cellular subsets are the main barrier to cure efforts. Antiretroviral therapy (ART) intensification by early initiation has been shown to enable post-treatment viral control in some cases but the underlying mechanisms are not fully understood. We hypothesized that ART initiated during the hyperacute phase of infection before peak will affect the size, decay dynamics and landscape characteristics of HIV-1 subtype C viral reservoirs. We studied 35 women at high risk of infection from Durban, South Africa identified with hyperacute HIV infection by twice weekly testing for plasma HIV-1 RNA. Study participants included 11 who started ART at a median of 456 (297-1203) days post onset of viremia (DPOV), and 24 who started ART at a median of 1 (1-3) DPOV. We used peripheral blood mononuclear cells (PBMC) to measure total HIV-1 DNA by ddPCR and to sequence reservoir viral genomes by full length individual proviral sequencing (FLIP-seq) from onset of detection of HIV up to 1 year post treatment initiation. Whereas ART in hyperacute infection blunted peak viremia compared to untreated individuals (p<0.0001), there was no difference in total HIV-1 DNA measured contemporaneously (p=0.104). There was a steady decline of total HIV DNA in early treated persons over 1 year of ART (p=0.0004), with no significant change observed in the late treated group. Total HIV-1 DNA after one year of treatment was lower in the early treated compared to the late treated group (p=0.02). Generation of 697 single viral genome sequences revealed a difference in the longitudinal proviral genetic landscape over one year between untreated, late treated, and early treated infection: the relative contribution of intact genomes to the total pool of HIV-1 DNA after 1 year was higher in untreated infection (31%) compared to late treated (14%) and early treated infection (0%). Treatment initiated in both late and early infection resulted in a more rapid decay of intact (13% and 51% per month) versus defective (2% and 35% per month) viral genomes. However, intact genomes were still observed one year post chronic treatment initiation in contrast to early treatment where intact genomes were no longer detectable. Moreover, early ART reduced phylogenetic diversity of intact genomes and limited the seeding and persistence of cytotoxic T lymphocyte immune escape variants in the reservoir. Overall, our results show that whereas ART initiated in hyperacute HIV-1 subtype C infection did not impact reservoir seeding, it was nevertheless associated with more rapid decay of intact viral genomes, decreased genetic complexity and immune escape in reservoirs, which could accelerate reservoir clearance when combined with other interventional strategies.

Auditory Cognition

Following vision, audition is often regarded as a secondary sensory system in the study of cognitive science and behavioral neuroscience. Auditory cognition tasks relate to the discernment of finite differences in frequency, duration, or rhythmic pattern. They suggest that there is a wide range of auditory functions required to mediate auditory responses. Auditory perception is the ability to interpret information that is received from the environment, and it is in this interpretation that audible frequency waves through the air or otherwise, follow a series of processes that allow for the acuity of sound. Several mechanisms are employed in the processing of acoustic information to extricate the many sources present and to assess the properties of individual events or sequences of events presenting themselves from a source. From a cognitive level, the sequential relations among events in longer sequences must be advanced to comprehend the nature of actions on objects that are extended in time.

Resources for innovative learning of anatomy and foot ossification: Graphic design and virtual reality.

This study addresses the ossification process of the foot, a topic of great relevance within podiatry courses. Understanding the chronology of foot bone formation is essential for evaluating pathological processes and establishing appropriate therapeutic actions to improve patient quality of life. The main objectives of this work are to understand the ossification process of the foot bones and to propose an appropriate didactic methodology for effective learning of this process. The individual ossification sequences of the foot bones were established and virtually recreated to make these processes more didactic and usable as teaching aids. The literature search was conducted using the PRISMA statement, focusing on terms, such as "bone ossification," "foot," and "bone development," and included relevant studies from medical databases. Updating the ossification ages and providing previously unavailable visual teaching material offers a useful tool for improving the teaching of this subject. It was found that, in general, the tarsal bones show significant differences in ossification ages between sexes, with later and slower ossification in males. These differences are statistically analyzed and presented in detailed comparative tables. The use of innovative teaching tools, such as virtual anatomical models, helps students to better understand the ossification process of foot bones. Implementing these tools in the podiatry curriculum not only facilitates knowledge acquisition but also enhances the quality of teaching and, consequently, the future clinical practice of students.

SpeciateIT and vSpeciateDB: novel, fast, and accurate per sequence 16S rRNA gene taxonomic classification of vaginal microbiota

BackgroundClustering of sequences into operational taxonomic units (OTUs) and denoising methods are a mainstream stopgap to taxonomically classifying large numbers of 16S rRNA gene sequences. Environment-specific reference databases generally yield optimal taxonomic assignment.ResultsWe developed SpeciateIT, a novel taxonomic classification tool which rapidly and accurately classifies individual amplicon sequences (https://github.com/Ravel-Laboratory/speciateIT). We also present vSpeciateDB, a custom reference database for the taxonomic classification of 16S rRNA gene amplicon sequences from vaginal microbiota. We show that SpeciateIT requires minimal computational resources relative to other algorithms and, when combined with vSpeciateDB, affords accurate species level classification in an environment-specific manner.ConclusionsHerein, two resources with new and practical importance are described. The novel classification algorithm, SpeciateIT, is based on 7th order Markov chain models and allows for fast and accurate per-sequence taxonomic assignments (as little as 10 min for 107 sequences). vSpeciateDB, a meticulously tailored reference database, stands as a vital and pragmatic contribution. Its significance lies in the superiority of this environment-specific database to provide more species-resolution over its universal counterparts.

Comparative Plastomics of Plantains (Plantago, Plantaginaceae) as a Tool for the Development of Species-Specific DNA Barcodes.

Plantago (plantains, Plantaginaceae) is a cosmopolitan genus including over 250 species used as functional foods, forage, and traditional medicine. Among them, Plantago lanceolata is commonly used as an ingredient of herbal products, but the close similarity to other Plantago species can cause misidentifications with potentially serious consequences for product safety/quality. To test the possibility of developing species-specific barcoding markers, we de novo assembled plastome sequences of individuals of Plantago argentea, Plantago atrata, P. lanceolata, and Plantago maritima. These genomes were characterized in comparison with both previously sequenced conspecific accessions and other publicly available plastomes, thus providing an assessment of both intraspecific and interspecific genetic variation in Plantago plastomes. Additionally, molecular evolutionary analyses indicated that eleven protein-coding genes involved in different plastid functions in Plantago plastomes underwent positive selection, suggesting they might have contributed to enhancing species' adaptation during the evolutionary history of Plantago. While the most variable mutational hotspots in Plantago plastomes were not suitable for the development of species-specific molecular markers, species-specific polymorphisms could discriminate P. lanceolata from its closest relatives. Taken together, these results highlight the potential of plastome sequencing for the development of molecular markers to improve the identification of species with relevance in herbal products.

A novel homozygous splicing mutation in AK7 causes multiple morphological abnormalities of sperm flagella in patients from consanguineous Pakistani families.

Multiple morphological abnormalities of the flagella (MMAF) represent a severe form of sperm defects leading to asthenozoospermia and male infertility. In this study, we identified a novel homozygous splicing mutation (c.871-4 ACA>A) in the adenylate kinase 7 (AK7) gene by whole-exome sequencing in infertile individuals. Spermatozoa from affected individuals exhibited typical MMAF characteristics, including coiled, bent, short, absent, and irregular flagella. Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella. Immunofluorescence staining confirmed the absence of AK7 protein from the patients' spermatozoa, validating the pathogenic nature of the mutation. This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans, expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.

Multisensory perceptual and causal inference is largely preserved in medicated post-acute individuals with schizophrenia.

Hallucinations and perceptual abnormalities in psychosis are thought to arise from imbalanced integration of prior information and sensory inputs. We combined psychophysics, Bayesian modeling, and electroencephalography (EEG) to investigate potential changes in perceptual and causal inference in response to audiovisual flash-beep sequences in medicated individuals with schizophrenia who exhibited limited psychotic symptoms. Seventeen participants with schizophrenia and 23 healthy controls reported either the number of flashes or the number of beeps of audiovisual sequences that varied in their audiovisual numeric disparity across trials. Both groups balanced sensory integration and segregation in line with Bayesian causal inference rather than resorting to simpler heuristics. Both also showed comparable weighting of prior information regarding the signals' causal structure, although the schizophrenia group slightly overweighted prior information about the number of flashes or beeps. At the neural level, both groups computed Bayesian causal inference through dynamic encoding of independent estimates of the flash and beep counts, followed by estimates that flexibly combine audiovisual inputs. Our results demonstrate that the core neurocomputational mechanisms for audiovisual perceptual and causal inference in number estimation tasks are largely preserved in our limited sample of medicated post-acute individuals with schizophrenia. Future research should explore whether these findings generalize to unmedicated patients with acute psychotic symptoms.

Enhancing Vaxign-DL for Vaccine Candidate Prediction with added ESM-Generated Features.

Many vaccine design programs have been developed, including our own machine learning approaches Vaxign-ML and Vaxign-DL. Using deep learning techniques, Vaxign-DL predicts bacterial protective antigens by calculating 509 biological and biomedical features from protein sequences. In this study, we first used the protein folding ESM program to calculate a set of 1,280 features from individual protein sequences, and then utilized the new set of features separately or in combination with the traditional set of 509 features to predict protective antigens. Our result showed that the usage of ESM-derived features alone was able to accurately predict vaccine antigens with a performance similar to the orginal Vaxign-DL prediction method, and the usage of the combined ESM-derived and orginal Vaxign-DL features significantly improved the prediction performance according to a set of seven scores including specificity, sensitivity, and AUROC. To further evaluate the updated methods, we conducted a Leave-One-Pathogen-Out Validation (LOPOV) study, and found that the usage of ESM-derived features significantly improved the the prediction of vaccine antigens from 10 bacterial pathogens. This research is the first reported study demonstrating the added value of protein folding features for vaccine antigen prediction.

Characterisation of novel KIR alleles: KIR3DL3*0070105, KIR3DL3*0130202, KIR3DL1*0080104 and KIR3DL1*0010121.

KIR3DL3*0070105, KIR3DL3*0130202, KIR3DL1*0080104 and KIR3DL1*0010121, identified by next generation sequencing in individuals from India.