Mammalian cell expressed recombinant trimeric spike protein is a potent vaccine antigen and confers near-complete protection against SARS-CoV-2 infection in Hamster.

Numerous vaccine candidates have emerged in the fight against SARS-CoV-2, yet the challenges posed by viral evolution and the evasion of vaccine-induced immunity persist. The development of broadly protective vaccines is essential in countering the threat posed by variants of concern (VoC) capable of eluding existing vaccine defenses. Among the diverse SARS-CoV-2 vaccine candidates, detailed characterization of those based on the expression of the entire spike protein in mammalian cells have been limited. In our study, we engineered a recombinant prefusion-stabilized trimeric spike protein antigen, IMT-CVAX, encoded by the IMT-C20 gene. This antigen was expressed utilizing a suspension mammalian cell line (CHO-S). The establishment of a stable cell line expressing IMT-CVAX involved the integration of the gene into the CHO genome, followed by the expression, purification, and characterization of the protein. To gauge the vaccine potential of adjuvanted IMT-CVAX, we conducted assessments in small animals. Analyses of blood collected from immunized animals included measurements of anti-spike IgG, SARS-CoV-2 neutralization, and responses from GC-B and Tfh cells. Furthermore, the protective efficacy of IMT-CVAX was evaluated using a Hamster challenge model. Our findings indicate that adjuvanted IMT-CVAX elicits an excellent immune response in both mice and hamsters. Notably, sera from animals immunized with IMT-CVAX effectively neutralize a diverse range of SARS-CoV-2 variants. Moreover, IMT-CVAX immunization conferred complete protection to hamsters against SARS-CoV-2 infection. In hACE2 transgenic mice, IMT-CVAX vaccination induced a robust response from GC-B and Tfh cells. Based on our preclinical model assessments, adjuvanted IMT-CVAX emerges as a highly efficacious vaccine candidate. This protein-subunit-based vaccine exhibits promise for clinical development, offering an affordable solution for both primary and heterologous immunization against SARS-CoV-2 variants.

Outcomes Analysis of 90Y Radioembolization for Tumors Other Than Metastatic Colorectal Cancer from the RESiN (Radiation-Emitting SIR-spheres in Non-resectable liver tumors) Registry.

PURPOSE: To characterize the response and survival outcomes of yttrium-90 transarterial radioembolization (90Y-TARE) for unresectable, liver-dominant metastases from primary neoplasms other than colorectal carcinoma. MATERIALS AND METHODS: This study included 1474 patients enrolled in the RESiN registry who received resin 90Y-TARE as part of their oncologic management for unresectable primary or secondary liver tumors (NCT02685631). 33% (481/1474) were treated for liver metastases of non-colorectal origin (m-nonCRC), compared to 34% (497/1474) treated for colorectal liver metastases (mCRC) and 34% (496/1474) treated for hepatocellular carcinoma (HCC). Treatment response and cancer survival probabilities were computed and compared for each primary cancer type. The Kaplan-Meier method and log-rank test were used to compare survival outcomes. RESULTS: Radiological responses were observed in 12 unique cancer types, mostly heavily pre-treated malignancies refractory to multiple lines of systemic therapies. The overall use of resin 90Y-TARE in m-nonCRC resulted in better treatment outcomes in terms of duration of response, progression free survival, time to progression and overall survival (P = 0.04, P = 0.02, P = 0.01, P = 0.04). Analyses of cancer cell types revealed that metastatic neuroendocrine tumor, sarcoma, and ovarian, renal, prostate, and breast cancers were associated with superior treatment outcomes, whereas worse treatment outcomes were observed in metastatic lung, gastric, pancreatic and esophageal cancers. CONCLUSION: Real-world data demonstrate the use of resin 90Y-TARE in m-nonCRC refractory to standard chemotherapy. For some cell types, this expanded use achieved superior treatment outcomes relative to the reference standard of mCRC, suggesting the need for inquiry into broadened indications for 90Y-TARE.

Loop-mediated isothermal amplification (LAMP) assay for early on-site detection of Group B Streptococcus infection in neonatal sepsis blood sample.

BACKGROUND: Neonatal sepsis, often attributed to Group B Streptococcus (GBS) infection, poses a critical health risk to infants, demanding rapid and accurate diagnostic approaches. Existing diagnostic approaches are dependent on traditional culture methods, a process that requires substantial time and has the potential to delay crucial therapeutic assessments. METHODS: This study introduces an innovative Loop-Mediated Isothermal Amplification (LAMP) assay for the early on-site detection of GBS infection from neonatal sepsis blood samples. To develop a LAMP assay, the primers are designed for the selective targeting of a highly conserved segment within the cfb gene encoding the CAMP factor in Streptococcus agalactiae ensuring high specificity. RESULTS: Rigorous optimization of reaction conditions, including temperature and incubation time, enhances the efficiency of the LAMP assay, enabling rapid and reliable GBS detection within a short timeframe. The diagnostic efficacy of the LAMP assay was evaluated using spiked blood samples by eliminating the DNA extraction step. The simplified colorimetric LAMP assay has the capability to detect S. agalactiae in a neonatal blood sample containing 2 CFU/mL during sepsis. Additionally, the LAMP assay effectively detected S. agalactiae in both the standard and spiked blood samples, with no detectable interference with blood. CONCLUSION: This optimised LAMP assay emerges as a promising tool for early GBS detection, offering a rapid and accurate on-site solution that has the potential to inform timely interventions and improve outcomes in neonatal sepsis cases.

Emergence of rare and low abundant anaerobic gut Firmicutes is associated with a significant downfall of Klebsiella in human colon cancer.

Gut bacterial dysbiosis has been linked to several gastrointestinal diseases, including deadly colorectal cancer (CRC), a leading cause of mortality in cancer patients. However, perturbation in gut bacteriome during colon cancer (CC, devoid of colorectal malignancy) remains poorly explored. Here, 16S rRNA gene amplicon sequencing was carried out for fecal DNA samples targeted to hypervariable V3-V4 region by employing MiSeq platform to explore the gut bacterial community shift in CC patients. While alpha diversity indices predicted high species richness and diversity, beta diversity showed marked gut bacterial compositional dissimilarity in CC versus healthy controls (HC, n = 10 each). We observed a significant (p < 0.05, Wilcoxon Rank-Sum test) emergence of low-abundant anaerobic taxa, including Parvimonas and Peptostreptococcus, in addition to Subdoligranulum, Coprococcus, Holdemanella, Solobacterium, Bilophila, Blautia, Dorea, Moryella and several unidentified taxa, mainly affiliated to Firmicutes, in CC patients. In addition, we also traced the emergence of putative probiotic taxon Slackia, belonging to Actinomycetota, in CC patients. The emergence of anaerobic Firmicutes in CC is accompanied by a significant (p < 0.05) decline in the Klebsiella, as determined through linear discriminant analysis effect size (LEfSe) and heat tree analyses. Shifts in core microbiome and variation in network correlation were also witnessed. Taken together, this study highlighted a significant and consistent emergence of rare anaerobic Firmicutes suggesting possible anaerobiosis driving gut microbial community shift, which could be exploited in designing diagnostic and therapeutic tools targeted to CC.

A sensory-motor theory of the neocortex.

Recent neurophysiological and neuroanatomical studies suggest a close interaction between sensory and motor processes across the neocortex. Here, I propose that the neocortex implements active predictive coding (APC): each cortical area estimates both latent sensory states and actions (including potentially abstract actions internal to the cortex), and the cortex as a whole predicts the consequences of actions at multiple hierarchical levels. Feedback from higher areas modulates the dynamics of state and action networks in lower areas. I show how the same APC architecture can explain (1) how we recognize an object and its parts using eye movements, (2) why perception seems stable despite eye movements, (3) how we learn compositional representations, for example, part-whole hierarchies, (4) how complex actions can be planned using simpler actions, and (5) how we form episodic memories of sensory-motor experiences and learn abstract concepts such as a family tree. I postulate a mapping of the APC model to the laminar architecture of the cortex and suggest possible roles for cortico-cortical and cortico-subcortical pathways.

First British and Irish Press Reports of Surgical Etherization.

In mid-December 1846, British and Irish newspapers reported the news of surgical etherization far more extensively than previously described. Reports about etherization had appeared at least 20 British and Irish newspapers in the days before Robert Liston's first operations under etherization on December 21, 1846. These reports were based on four separate accounts, 2 of which could be traced to New York, and 1 account had been published in a Parisian newspaper Galignani's Messenger on December 9, 1846.

Management of coagulopathy among patients with cirrhosis undergoing upper endoscopy and paracentesis: Persistent gaps and areas of consensus in a multispecialty Delphi.

Patients with cirrhosis have abnormal coagulation indices such as a high international normalized ratio and low platelet count, but these do not correlate well with periprocedural bleeding risk. We sought to develop a consensus among the multiple stakeholders in cirrhosis care to inform process measures that can help improve the quality of the periprocedural management of coagulopathy in cirrhosis. We identified candidate process measures for periprocedural coagulopathy management in multiple contexts relating to the performance of paracentesis and upper endoscopy. An 11-member panel with content expertise was convened. It included nominees from professional societies for interventional radiology, transfusion medicine, and anesthesia as well as representatives from hematology, emergency medicine, transplant surgery, and community practice. Each measure was evaluated for agreement using a modified Delphi approach (3 rounds of rating) to define the final set of measures. Out of 286 possible measures, 33 measures made the final set. International normalized ratio testing was not required for diagnostic or therapeutic paracentesis as well as diagnostic endoscopy. Plasma transfusion should be avoided for all paracenteses and diagnostic endoscopy. No consensus was achieved for these items in therapeutic intent or emergent endoscopy. The risks of prophylactic platelet transfusions exceed their benefits for outpatient diagnostic paracentesis and diagnostic endosopies. For the other procedures examined, the risks outweigh benefits when platelet count is >20,000/mm 3 . It is uncertain whether risks outweigh benefits below 20,000/mm 3 in other contexts. No consensus was achieved on whether it was permissible to continue or stop systemic anticoagulation. Continuous aspirin was permissible for each procedure. Clopidogrel was permissible for diagnostic and therapeutic paracentesis and diagnostic endoscopy. We found many areas of consensus that may serve as a foundation for a common set of practice metrics for the periprocedural management of coagulopathy in cirrhosis.

'On the inhalation of the vapour of Æther, with cases': The first paper on anaesthesia read before a medical society in Australia.

On 7 September 1847, in Melbourne in the Port Phillip District of the Colony of New South Wales, David John Thomas (1813-1871) presented a paper, 'On the inhalation of the vapour of Æther, with cases', at an ordinary monthly meeting of the Port Phillip Medical Association. This is the earliest known presentation of a paper on etherisation in Australia. The partial publication of the manuscript in October 1847 in the Australian Medical Journal may have led to it being returned to Thomas in Melbourne. The handwritten manuscript is now preserved in the Medical History Museum, University of Melbourne, Melbourne, Victoria. A transcript of the complete manuscript is now recorded with relevant historical notes.

Appearance and Prevalence of JN.1 SARS-CoV-2 Variant in India and Its Clinical Profile in the State of Maharashtra.

BACKGROUND: In August 2023, the BA.2.86 SARS-CoV-2 variant, with over 30 spike protein mutations, emerged amidst the global dominance of XBB sub-lineages. It evolved into JN.1 by late 2023, spreading across 71 countries. JN.1, distinct for its L455S mutation, significantly dominated global sequences, raising concerns over its transmission and clinical impact. The study investigates JN.1's clinical severity and its effect on hospital admissions in Maharashtra, India. METHODOLOGY: The present study involved 3,150 curated Indian SARS-CoV-2 whole genome sequences with collection dates between 1st August 2023 and 15th January 2024. Lineage and phylogenetic analysis of sequences was performed using Nextclade. Telephonic interviews were conducted to confirm the demographic details and obtain clinical information on the JN.1* (* indicates JN.1 and all its sub-lineages) cases. The obtained data were recorded and analyzed using Microsoft® Excel (Microsoft Corporation, Redmond, WA). RESULTS: Out of 3,150 sequences analyzed, JN.1* was the most common lineage (2377/3150, 75.46%), followed by XBB.2.3* (281/3150, 8.92%) and XBB.1.16* (187/3150, 5.94%). In India, it was first identified on 6th October 2023, in Kerala. The highest proportion of JN.1* sequences originated from Maharashtra (628/2377, 26.42%), followed by West Bengal (320/2377, 13.46%), Andhra Pradesh (293/2377, 12.33%), Kerala (288/2377, 12.12%), and Karnataka (285/2377, 11.99%). In Maharashtra, the JN.1* variant was first identified on 23rd November 2023. A total of 279 JN.1* cases were included in the clinical study. Of these, 95.34% (266/279) had symptomatic disease with mild symptoms; cold (187/279, 67.03%) being the most common symptom, followed by fever (156/279, 55.91%), cough (114/279, 40.86%), and headache (28/279, 15.64%). Of all the cases, 13.26% (37/279) required institutional quarantine or hospitalization, and the rest were isolated at home. Among the hospitalized patients, 54.05% (20/37) cases were given conservative treatment while 45.95% (17/37) cases required supplemental oxygen therapy. Regarding the vaccination status, 94.26% (263/279) of cases received at least one dose of the COVID-19 vaccine, while 5.02% (14/279) were not vaccinated, of which most were children aged zero to nine years (5/14, 35.71%). The overall recovery rate among JN.1* cases was 98.57% (275/279), with 1.43% (4/279) cases succumbing to the disease. CONCLUSION: The JN.1* variant, the dominant variant in India, exhibits clinical features similar to previous circulating variants in Maharashtra without increased severity. Its notable transmissibility underscores the importance of studying the ongoing viral evolution. The pressing necessity for swift identification and the clinical features of new variants is essential for effective public health response.

Neurocomputational mechanisms involved in adaptation to fluctuating intentions of others.

Humans frequently interact with agents whose intentions can fluctuate between competition and cooperation over time. It is unclear how the brain adapts to fluctuating intentions of others when the nature of the interactions (to cooperate or compete) is not explicitly and truthfully signaled. Here, we use model-based fMRI and a task in which participants thought they were playing with another player. In fact, they played with an algorithm that alternated without signaling between cooperative and competitive strategies. We show that a neurocomputational mechanism with arbitration between competitive and cooperative experts outperforms other learning models in predicting choice behavior. At the brain level, the fMRI results show that the ventral striatum and ventromedial prefrontal cortex track the difference of reliability between these experts. When attributing competitive intentions, we find increased coupling between these regions and a network that distinguishes prediction errors related to competition and cooperation. These findings provide a neurocomputational account of how the brain arbitrates dynamically between cooperative and competitive intentions when making adaptive social decisions.

Braided silk sutures coated with photoreduced silver nanoparticles for eradicating Staphylococcus aureus and Streptococcus mutans infections.

BACKGROUND: Infections resulting from surgical procedures and wound closures continue to pose significant challenges in healthcare settings. To address this issue, the investigators have developed antibacterial non-resorbable braided silk sutures using in situ deposited silver nanoparticles (AgNPs) and investigated their efficacy in eradicating Staphylococcus aureus and Streptococcus mutans infections. METHODS: The braided silk sutures were modified through a simple and efficient in situ photoreduction method, resulting in the uniform distribution of AgNPs along the suture surface. The synthesized AgNPs were characterized using scanning electron microscopy (SEM), dynamic light scattering analysis (DLS) and Fourier Transform Infrared Spectroscopy analysis (FTIR) confirming their successful integration onto the silk sutures. The antibacterial activity of the nanoparticle coated sutures were compared and evaluated with non-coated braided silk sutures through in vitro assays against both S. aureus and S. mutans. RESULTS: The surface and cross-sectional analysis of the treated sutures revealed a uniform and homogeneous distribution of silver particles achieved through the photoreduction of silver solution. This observation confirms the successful coating of silver nanoparticles (AgNPs) on the sutures. The antimicrobial studies conducted, demonstrated significant reductions in bacterial colonies when exposed to the silver nanoparticle-coated sutures. Notably, the width of the inhibition zone surrounding the coated sutures remained consistently wide and stable for duration up to 7 days. This sustained and robust inhibitory effect against gram-positive bacteria, specifically S. aureus and S. mutans, serves as strong evidence of the antibacterial efficacy of the coated sutures. CONCLUSION: The coating of silk sutures with AgNPs provided a significant and effective antibacterial capacity to the surgical sutures, with this activity being sustained for a period of 7 days. This suggests that AgNPs-in situ photoreduction deposited sutures have the potential to effectively manage S. aureus and S. mutans infections.

Household Transmission of SARS-CoV-2 in the Third Wave of the Pandemic with Special Reference to Clinico-epidemiological Characteristics.

Background: Coronavirus disease 2019 (COVID-19) pandemic began in India in 2020. Despite successful vaccination, cases again started increasing from mid-December 2021. Therefore, this study was undertaken to find out the clinico-epidemiological characteristics and effectiveness of vaccination in the household transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in and around Pune. Material and Methods: All samples received from December 15, 2021, till February 15, 2022, were included in the study. Samples received in viral transport medium (VTM) were extracted by the MagMAX RNA Extraction Kit, and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed by the CoviPath Kit as per kit guidelines. Values of nucleocapsid (N) gene and open reading frame (ORF) less than 37 were considered positive. Clinico-epidemiological data were analyzed from the sample referral form (SRF). Results: A total of 712 of 1032 household contacts of 271 families were positive. When geographical areas were compared, it was found that rural areas were affected more (63.76%) as compared to urban areas (36.24%). Males were more affected than females. The most commonly affected age group was 41-50 years (26.54%). Small families were found to have more household transmission. Mild symptoms were present in 97.89%. Among 271 infected individuals, seven were admitted to hospital, of which one patient died due to pneumonia. Two doses of vaccination were completed in 93.95%, and 3.79% had taken booster dose. Conclusions: Data from this study showed that a high rate of transmission was observed in household contact despite two doses of vaccination. However, these vaccinated individuals had mild symptoms, maybe due to the effect of vaccination and infecting variant omicron.

Asymptomatic spontaneous expulsion of a long foreign body through the gastrointestinal tract - a curious case report.

Foreign body ingestion and its natural elimination are common in children. However, this is uncommon for long foreign bodies. Here, we report the spontaneous removal of an ingested pencil in an asymptomatic child. To our knowledge, this is the first case report of asymptomatic spontaneous elimination of a normally-sized ingested pencil. A 7-year-old male child presented with a history of ingestion of a pencil 4 hours back, without any complaints. Immediate abdominal radiography revealed a pencil in the stomach with an estimated length of approximately 10 cm and no signs of complications. He was conservatively treated under a semi-solid diet, presumably due to lack of available endoscopic option. Subsequently, he passed the pencil in stool within 24 hours of ingestion. He was asymptomatic and playful during the course and at discharge. Conservative management of a quickly moving long foreign body initially located below the esophagus in an asymptomatic child is possible with the help of imaging guidance, particularly in settings lacking an endoscopy. Although, this should not be considered a norm. However, this suggests that the treatment of ingested foreign bodies must be individualized. Thus, multiple factors related to the child and the foreign body must be assessed before committing to invasive procedures like laparotomy. Similarly, plain X-rays can be helpful even for radiolucent foreign bodies, for diagnosis and ruling out complications. All of these are vital in underdeveloped countries, where endoscopy and computed tomography facilities might be either lacking or unaffordable by patients.

Dynamic predictive coding: A model of hierarchical sequence learning and prediction in the neocortex.

We introduce dynamic predictive coding, a hierarchical model of spatiotemporal prediction and sequence learning in the neocortex. The model assumes that higher cortical levels modulate the temporal dynamics of lower levels, correcting their predictions of dynamics using prediction errors. As a result, lower levels form representations that encode sequences at shorter timescales (e.g., a single step) while higher levels form representations that encode sequences at longer timescales (e.g., an entire sequence). We tested this model using a two-level neural network, where the top-down modulation creates low-dimensional combinations of a set of learned temporal dynamics to explain input sequences. When trained on natural videos, the lower-level model neurons developed space-time receptive fields similar to those of simple cells in the primary visual cortex while the higher-level responses spanned longer timescales, mimicking temporal response hierarchies in the cortex. Additionally, the network's hierarchical sequence representation exhibited both predictive and postdictive effects resembling those observed in visual motion processing in humans (e.g., in the flash-lag illusion). When coupled with an associative memory emulating the role of the hippocampus, the model allowed episodic memories to be stored and retrieved, supporting cue-triggered recall of an input sequence similar to activity recall in the visual cortex. When extended to three hierarchical levels, the model learned progressively more abstract temporal representations along the hierarchy. Taken together, our results suggest that cortical processing and learning of sequences can be interpreted as dynamic predictive coding based on a hierarchical spatiotemporal generative model of the visual world.

The First Etherization in England: New Research Regarding the Identity of the First Patient, Miss Lonsdale.

On December 19, 1846, at the London home of Francis Boott, dentist James Robinson administered the vapor of diethyl ether to a young female patient named Miss Lonsdale. This was the earliest known attempt in England to provide painless operating conditions for a dental extraction, and it was successful. Many authors have since written much about Boott and Robinson, but scarcely anything is known about Miss Lonsdale. In contemporaneous accounts of the event, Robinson referred to his patient as a "young person" and a "young lady"; Boott, however, named her, suggesting that she was publicly recognizable. Our initial attempt to identify Miss Lonsdale was based on genealogical, United Kingdom Census, and other public records, using selection criteria based on age, name recognition, familial relationships, and London addresses. This produced 7 possible candidates from publicly recognizable families, though none was notable in her own right. Our second attempt was based primarily on contemporaneous newspaper records, among which were published 2 private letters in which Boott referred to Robinson's patient as a "girl." We found that "Miss Lonsdale" was the publicly recognizable name of 2 young stage-performing sisters, Adeline Lonsdale, a danseuse, and Annie Lonsdale, an actor-comedienne. Both subsequently emigrated to the United States where they were well-known stage performers. Accordingly, we suggest that both are highly probable candidates for that etherized patient, with the younger sister Adeline then more publicly recognizable. However, no records were found that directly associated any of the Miss Lonsdale candidates with that first dental anesthetic in England.

Synergistic effects of COVID-19 and Pseudomonas aeruginosa in chronic obstructive pulmonary disease: a polymicrobial perspective.

This article discusses the connection between the novel coronavirus disease 2019 (COVID-19) caused by the coronavirus-2 (SARS-CoV-2) and chronic obstructive pulmonary disease (COPD). COPD is a multifaceted respiratory illness that is typically observed in individuals with chronic exposure to chemical irritants or severe lung damage caused by various pathogens, including SARS-CoV-2 and Pseudomonas aeruginosa. The pathogenesis of COPD is complex, involving a variety of genotypes and phenotypic characteristics that result in severe co-infections and a poor prognosis if not properly managed. We focus on the role of SARS-CoV-2 infection in severe COPD exacerbations in connection to P.  aeruginosa infection, covering pathogenesis, diagnosis, and therapy. This review also includes a thorough structural overview of COPD and recent developments in understanding its complicated and chronic nature. While COVID-19 is clearly linked to emphysema and chronic bronchitis at different stages of the disease, our understanding of the precise interaction between microbial infections during COPD, particularly with SARS-CoV-2 in the lungs, remains inadequate. Therefore, it is crucial to understand the host-pathogen relationship from the clinician's perspective in order to effectively manage COPD. This article aims to provide a comprehensive overview of the subject matter to assist clinicians in their efforts to improve the treatment and management of COPD, especially in light of the COVID-19 pandemic.

Targeting the Pseudomonas aeruginosa quorum sensing system to inhibit virulence factors and eradicate biofilm formation using AHL-analogue phytochemicals.

Quorum sensing plays a major role in the expression of virulence and development of biofilm in the human pathogen Pseudomonas aeruginosa. Natural compounds are well-known for their antibacterial characteristics by blocking various metabolic pathways. The goal of this study is to find natural compounds that mimic AHL (Acyl homoserine lactone) and suppress virulence in P. aeruginosa, which is triggered by quorum sensing-dependent pathways as an alternative drug development strategy. To support this rationale, functional network analysis and in silico investigations were carried out to find natural AHL analogues, followed by molecular docking studies. Out of the 16 top-hit AHL analogues derived from phytochemicals, seven ligands were found to bind to the quorum sensing activator proteins. Cassialactone, an AHL analogue, exhibited the highest binding affinity for RhlI, RhlR, and PqsE of P. aeruginosa, with a docking score of -9.4, -8.9, and -8.7 kcal/mol, respectively. 2(5H)-Furanone, a well-known inhibitor, was also docked to compare the docking score and intermolecular interactions between the ligand and the target protein. Furthermore, molecular dynamics simulations and binding free energy calculations were performed to determine the stability of the docked complexes. Additionally, the ADME properties of the analogues were also analyzed to evaluate the pharmacological parameters. Functional network analysis further showed that the interconnectedness of proteins such as RhlI, RhlR, LasI, and PqsE with the virulence and biofilm phenotype of the pathogen could offer potential as a therapeutic target.Communicated by Ramaswamy H. Sarma.

Active Predictive Coding: A Unifying Neural Model for Active Perception, Compositional Learning, and Hierarchical Planning.

There is growing interest in predictive coding as a model of how the brain learns through predictions and prediction errors. Predictive coding models have traditionally focused on sensory coding and perception. Here we introduce active predictive coding (APC) as a unifying model for perception, action, and cognition. The APC model addresses important open problems in cognitive science and AI, including (1) how we learn compositional representations (e.g., part-whole hierarchies for equivariant vision) and (2) how we solve large-scale planning problems, which are hard for traditional reinforcement learning, by composing complex state dynamics and abstract actions from simpler dynamics and primitive actions. By using hypernetworks, self-supervised learning, and reinforcement learning, APC learns hierarchical world models by combining task-invariant state transition networks and task-dependent policy networks at multiple abstraction levels. We illustrate the applicability of the APC model to active visual perception and hierarchical planning. Our results represent, to our knowledge, the first proof-of-concept demonstration of a unified approach to addressing the part-whole learning problem in vision, the nested reference frames learning problem in cognition, and the integrated state-action hierarchy learning problem in reinforcement learning.

Local field potentials and single unit dynamics in motor cortex of unconstrained macaques during different behavioral states.

Different sleep stages have been shown to be vital for a variety of brain functions, including learning, memory, and skill consolidation. However, our understanding of neural dynamics during sleep and the role of prominent LFP frequency bands remain incomplete. To elucidate such dynamics and differences between behavioral states we collected multichannel LFP and spike data in primary motor cortex of unconstrained macaques for up to 24 h using a head-fixed brain-computer interface (Neurochip3). Each 8-s bin of time was classified into awake-moving (Move), awake-resting (Rest), REM sleep (REM), or non-REM sleep (NREM) by using dimensionality reduction and clustering on the average spectral density and the acceleration of the head. LFP power showed high delta during NREM, high theta during REM, and high beta when the animal was awake. Cross-frequency phase-amplitude coupling typically showed higher coupling during NREM between all pairs of frequency bands. Two notable exceptions were high delta-high gamma and theta-high gamma coupling during Move, and high theta-beta coupling during REM. Single units showed decreased firing rate during NREM, though with increased short ISIs compared to other states. Spike-LFP synchrony showed high delta synchrony during Move, and higher coupling with all other frequency bands during NREM. These results altogether reveal potential roles and functions of different LFP bands that have previously been unexplored.