Combined protection of vaccination and nirmatrelvir-ritonavir against hospitalization in adults with COVID-19.

Among U.S. adults at risk for severe COVID-19 in Epic Cosmos, the lowest rate of hospitalization was among those receiving three or more mRNA vaccine doses and nirmatrelvir-ritonavir (aHR 0.22, 95%CI: 0.19-0.24). Adults who are at high-risk of severe COVID-19 disease, including vaccinated persons, should be considered for antiviral treatment.

MiCId GUI: The Graphical User Interface for MiCId, a Fast Microorganism Classification and Identification Workflow with Accurate Statistics and High Recall.

Although many user-friendly workflows exist for identifications of peptides and proteins in mass-spectrometry-based proteomics, there is a need of easy to use, fast, and accurate workflows for identifications of microorganisms, antimicrobial resistant proteins, and biomass estimation. Identification of microorganisms is a computationally demanding task that requires querying thousands of MS/MS spectra in a database containing thousands to tens of thousands of microorganisms. Existing software can't handle such a task in a time efficient manner, taking hours to process a single MS/MS experiment. Another paramount factor to consider is the necessity of accurate statistical significance to properly control the proportion of false discoveries among the identified microorganisms, and antimicrobial-resistant proteins, and to provide robust biomass estimation. Recently, we have developed Microorganism Classification and Identification (MiCId) workflow that assigns accurate statistical significance to identified microorganisms, antimicrobial-resistant proteins, and biomass estimation. MiCId's workflow is also computationally efficient, taking about 6-17 minutes to process a tandem mass-spectrometry (MS/MS) experiment using computer resources that are available in most laptop and desktop computers, making it a portable workflow. To make data analysis accessible to a broader range of users, beyond users familiar with the Linux environment, we have developed a graphical user interface (GUI) for MiCId's workflow. The GUI brings to users all the functionality of MiCId's workflow in a friendly interface along with tools for data analysis, visualization, and to export results.

Olfaction and reaction: The role of olfactory and hypothalamic investment in the antipredator responses to chemical alarm cues by northern redbelly dace.

Neuroplasticity enables teleosts to promote or downregulate the growth of their brains regionally. To compensate for the effects of predation pressure, teleosts may alter their brain morphology and behavioral responses to mitigate its impact on individual fitness. High-predation environments often promote specific patterns of brain growth and produce bolder and more proactive populations. Owing to the expense of maintaining neural tissue, relative size indicates the regions most relied upon. In northern redbelly dace Chrosomus eos, as little as 2 weeks of elevated predation pressure, resulted in increased investment in their olfactory bulbs and optic tecta, while the imposition of captivity produced smaller, less symmetric hypothalami. Taken together, these results suggest that an individual could potentially become better able to detect a threat, and simultaneously less inclined to react to it, making the impact of either change in isolation is difficult to discern. Here, we compared interindividual variation in gross brain morphology, risk-taking tactics in a novel arena (shy-bold personality), and responding to olfactory cues (proactive/reactive stress-coping style). We hypothesized that olfactory investment would positively correlate with response intensity to predator cue concentration and respond across a wider range of cue concentrations, while hypothalamus size would correlate with shyness and reactivity. Exposure to heightened risk produced more bold/proactive individuals, with larger olfactory bulbs and smaller hypothalami. However, the direction of the correlation between hypothalamus size and behavior varied by treatment, and olfactory investment only corresponded with response intensity amongst proactive individuals. Our findings illustrate the potential pitfalls of relating gross brain morphology to complex behavior and suggest that stress-coping style is a relevant consideration in future studies.

Paxlovid Associated with Decreased Hospitalization Rate Among Adults with COVID-19 - United States, April-September 2022.

Nirmatrelvir-ritonavir (Paxlovid), an oral antiviral treatment, is authorized for adults with mild-to-moderate COVID-19 who are at increased risk for progression to severe illness. However, real-world evidence on the benefit of Paxlovid, according to vaccination status, age group, and underlying health conditions, is limited. To examine the benefit of Paxlovid in adults aged ≥18 years in the United States, a large electronic health record (EHR) data set (Cosmos†) was analyzed to assess the association between receiving a prescription for Paxlovid and hospitalization with a COVID-19 diagnosis in the ensuing 30 days. A Cox proportional hazards model was used to estimate this association, adjusted for demographic characteristics, geographic location, vaccination, previous infection, and number of underlying health conditions. Among 699,848 adults aged ≥18 years eligible for Paxlovid during April-August 2022, 28.4% received a Paxlovid prescription within 5 days of COVID-19 diagnosis. Being prescribed Paxlovid was associated with a lower hospitalization rate among the overall study population (adjusted hazard ratio [aHR] = 0.49), among those who had received ≥3 mRNA COVID-19 vaccines (aHR = 0.50), and across age groups (18-49 years: aHR = 0.59; 50-64 years: aHR = 0.40; and ≥65 years: aHR = 0.53). Paxlovid should be prescribed to eligible adults to reduce the risk of COVID-19-associated hospitalization.

Short-term captivity drives hypothalamic plasticity and asymmetry in wild-caught northern red bellied dace (Chrosomus eos).

Teleost fish are neuroplastic and are known to alter their brain morphology and behaviour in response to environmental change such as an increase in predation pressure. The hypothalamus plays a key role in regulating behavioural responses to predation risk. In this study, wild-caught northern red bellied dace (Chrosomus eos) developed smaller and less symmetric hypothalami when held in captivity for 14 days; both measures correlated with boldness in a latency to emerge test. This study's results highlight the potential impact of short-term holding conditions on brains and behaviour.

Diurnal variation in opsin expression and common housekeeping genes necessitates comprehensive normalization methods for quantitative real-time PCR analyses.

To determine the visual sensitivities of an organism of interest, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is often used to quantify expression of the light-sensitive opsins in the retina. While qRT-PCR is an affordable, high-throughput method for measuring expression, it comes with inherent normalization issues that affect the interpretation of results, especially as opsin expression can vary greatly based on developmental stage, light environment or diurnal cycles. We tested for diurnal cycles of opsin expression over a period of 24 hr at 1-hr increments and examined how normalization affects a data set with fluctuating expression levels using qRT-PCR and transcriptome data from the retinae of the cichlid Pelmatolapia mariae. We compared five methods of normalizing opsin expression relative to (a) the average of three stably expressed housekeeping genes (Ube2z, EF1-α and ß-actin), (b) total RNA concentration, (c) GNAT2, (the cone-specific subunit of transducin), (d) total opsin expression and (e) only opsins expressed in the same cone type. Normalizing by proportion of cone type produced the least variation and would be best for removing time-of-day variation. In contrast, normalizing by housekeeping genes produced the highest daily variation in expression and demonstrated that the peak of cone opsin expression was in the late afternoon. A weighted correlation network analysis showed that the expression of different cone opsins follows a very similar daily cycle. With the knowledge of how these normalization methods affect opsin expression data, we make recommendations for designing sampling approaches and quantification methods based upon the scientific question being examined.

A graphical user interface for RAId, a knowledge integrated proteomics analysis suite with accurate statistics.

OBJECTIVE: RAId is a software package that has been actively developed for the past 10 years for computationally and visually analyzing MS/MS data. Founded on rigorous statistical methods, RAId's core program computes accurate E-values for peptides and proteins identified during database searches. Making this robust tool readily accessible for the proteomics community by developing a graphical user interface (GUI) is our main goal here. RESULTS: We have constructed a graphical user interface to facilitate the use of RAId on users' local machines. Written in Java, RAId_GUI not only makes easy executions of RAId but also provides tools for data/spectra visualization, MS-product analysis, molecular isotopic distribution analysis, and graphing the retrieval versus the proportion of false discoveries. The results viewer displays and allows the users to download the analyses results. Both the knowledge-integrated organismal databases and the code package (containing source code, the graphical user interface, and a user manual) are available for download at https://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads/raid.html .

Risk-induced neophobia: does sensory modality matter?

Recent studies have documented that exposure to high levels of background risk can induce neophobic predator avoidance in prey animals, whereby they respond to any novel cue with an anti-predator response. Such phenotypically plastic predator avoidance may allow prey to maximize anti-predator benefits in variable risk environments. It remains poorly understood whether risk assessment information from different sensory modalities can be integrated to induce generalized, cross-sensory system neophobic responses. Here, we directly test this hypothesis by exposing juvenile convict cichlids (Amatitlania nigrofasciata) to high- versus low-risk environments using either conspecific alarm cue (chemosensory risk) or a model avian predator (visual/mechanical risk) and testing their response to a novel chemosensory cue (Experiment 1) or visual cue (Experiment 2). Our results suggest that regardless of the sensory modality used to increased perceived risk, cichlids pre-exposed to high-risk conditions exhibited increased predator avoidance in response to any novel visual or chemical cue. As expected, cichlids pre-exposed to low-risk conditions did not display any neophobic responses. Our results suggest that induced neophobia is not cue specific; rather, it may function as a generalized response to perceived predation risk.

Retention of neophobic predator recognition in juvenile convict cichlids: effects of background risk and recent experience.

Exposure to conditions of elevated predation risk, even for relatively short periods, has been shown to induce neophobic responses to novel predators. Such phenotypically plastic responses should allow prey to exhibit costly anti-predator behaviour to novel cues only in situations where the risk of predation is high. While there is evidence that the level of background risk shapes the strength of induced neophobia, we know little about how long neophobic responses are retained. Here we exposed juvenile convict cichlids (Amatitlania nigrofasciata) to three background levels of short-term background risk and then tested their responses to novel predator odours. Cichlids exposed to low risk did not show neophobic responses, while those exposed to intermediate and high risk did. Using extinction trials, we demonstrate that the retention of neophobic responses is greater among cichlids exposed to high versus intermediate predation risk conditions. Moreover, we found much longer retention of the neophobic responses when cichlids were tested a single time compared to when they were tested repeatedly in the extinction trials. This work supports the prediction that neophobic responses to specific odours are relatively long lasting but can quickly wane if the cues are experienced repeatedly without them being associated with risk. It is clear that background level of risk and the frequency of exposure to novel cues are crucial factors in determining the retention of risk-related information among prey.