[Respiratory infections: when a horse is actually a zebra]. / Infections respiratoires : quand un cheval est en fait un zèbre.

While most episodes of community-acquired pneumonia are caused by Streptococcus pneumoniae and respiratory viruses, other atypical pathogens can also be responsible for lung infections. The Infectious Diseases Service of the Lausanne University Hospital (CHUV) organizes an annual meeting aimed at general practitioners, during which interesting clinical cases are presented. In this article, we summarize five cases of community-aquired respiratory infection due to atypical pathogens that were presented during the 2023 meeting, each with a particular teaching point. Although these infections are rare, expanding the differential diagnosis in cases of suboptimal response to therapy or particular exposures is warranted.

La plupart des épisodes de pneumonie acquise en communauté sont causés par Streptococcus pneumoniae et des virus respiratoires, mais d'autres agents pathogènes atypiques peuvent également être responsables d'infections pulmonaires. Le Service des maladies infectieuses du Centre hospitalier universitaire vaudois (CHUV) organise une réunion annuelle destinée aux médecins généralistes, au cours de laquelle des cas cliniques intéressants sont présentés. Dans cet article, nous résumons cinq cas d'infections respiratoires communautaires dus à des agents pathogènes atypiques présentés lors de la réunion de 2023, chacun avec un enseignement particulier. Bien que ces infections soient rares, élargir le diagnostic différentiel en cas de réponse thérapeutique suboptimale ou d'expositions particulières est justifié.

Association of persistent positive blood cultures and infective endocarditis: A cohort study among patients with suspected infective endocarditis.

OBJECTIVES: To ascertain whether infective endocarditis (IE) was associated with persistent bacteraemia/candidaemia among patients with suspected IE. METHODS: This study included bacteraemic/candidaemic adult patients with echocardiography and follow-up blood cultures. Persistent bacteraemia/candidaemia was defined as continued positive blood cultures with the same microorganism for 48 h or more after antibiotic treatment initiation. Each case was classified for IE by the Endocarditis Team. RESULTS: Among 1962 episodes of suspected IE, IE (605; 31%) was the most prevalent infection type. Persistent bacteraemia/candidaemia was observed in 426 (22%) episodes. Persistent bacteraemia was more common among episodes with Staphylococcus aureus bacteraemia compared to episodes with positive blood cultures for other pathogens (32%, 298/933 vs 12%, 128/1029; P < 0.001). Multivariable analysis demonstrated that cardiac predisposing factors (aOR 1.84, 95% CI 1.31-2.60), community or non-nosocomial healthcare-associated (2.85, 2.10-3.88), bacteraemia by high-risk bacteria, such as S. aureus, streptococci, enterococci or HACEK (1.84, 1.31-2.60), two or more positive sets of index blood cultures (6.99, 4.60-10.63), persistent bacteraemia/candidaemia for 48 h from antimicrobial treatment initiation (1.43, 1.05-1.93), embolic events within 48h from antimicrobial treatment initiation (12.81, 9.43-17.41), and immunological phenomena (3.87, 1.09-1.78) were associated with infective endocarditis. CONCLUSIONS: IE was associated with persistent bacteraemia/candidaemia, along with other commonly associated factors.

Diving into the proteomic atlas of SARS-CoV-2 infected cells.

The COVID-19 pandemic was initiated by the rapid spread of a SARS-CoV-2 strain. Though mainly classified as a respiratory disease, SARS-CoV-2 infects multiple tissues throughout the human body, leading to a wide range of symptoms in patients. To better understand how SARS-CoV-2 affects the proteome from cells with different ontologies, this work generated an infectome atlas of 9 cell models, including cells from brain, blood, digestive system, and adipocyte tissue. Our data shows that SARS-CoV-2 infection mainly trigger dysregulations on proteins related to cellular structure and energy metabolism. Despite these pivotal processes, heterogeneity of infection was also observed, highlighting many proteins and pathways uniquely dysregulated in one cell type or ontological group. These data have been made searchable online via a tool that will permit future submissions of proteomic data ( https://reisdeoliveira.shinyapps.io/Infectome_App/ ) to enrich and expand this knowledgebase.

Between neurons and networks: investigating mesoscale brain connectivity in neurological and psychiatric disorders.

The study of brain connectivity has been a cornerstone in understanding the complexities of neurological and psychiatric disorders. It has provided invaluable insights into the functional architecture of the brain and how it is perturbed in disorders. However, a persistent challenge has been achieving the proper spatial resolution, and developing computational algorithms to address biological questions at the multi-cellular level, a scale often referred to as the mesoscale. Historically, neuroimaging studies of brain connectivity have predominantly focused on the macroscale, providing insights into inter-regional brain connections but often falling short of resolving the intricacies of neural circuitry at the cellular or mesoscale level. This limitation has hindered our ability to fully comprehend the underlying mechanisms of neurological and psychiatric disorders and to develop targeted interventions. In light of this issue, our review manuscript seeks to bridge this critical gap by delving into the domain of mesoscale neuroimaging. We aim to provide a comprehensive overview of conditions affected by aberrant neural connections, image acquisition techniques, feature extraction, and data analysis methods that are specifically tailored to the mesoscale. We further delineate the potential of brain connectivity research to elucidate complex biological questions, with a particular focus on schizophrenia and epilepsy. This review encompasses topics such as dendritic spine quantification, single neuron morphology, and brain region connectivity. We aim to showcase the applicability and significance of mesoscale neuroimaging techniques in the field of neuroscience, highlighting their potential for gaining insights into the complexities of neurological and psychiatric disorders.

A review of biomineralization in healing concrete: Mechanism, biodiversity, and application.

Concrete is the main ingredient in construction, but it inevitably fractures during its service life, requiring a large amount of cement and aggregate for maintenance. Concrete healing through biomineralization can repair cracks and improve the durability of concrete, which is conducive to saving raw materials and reducing carbon emissions. This paper reviews the biodiversity of microorganisms capable of precipitating mineralization to repair the concrete and their mineralization ability under different conditions. To better understand the mass transfer process of precipitates, two biomineralization mechanisms, microbially-controlled mineralization and microbially-induced mineralization, have been briefly described. The application of microorganisms in the field of healing concrete, comprising passive healing and intrinsic healing, is discussed. The key insight on the interaction between cementitious materials and microorganisms is the main approach for developing novel self-healing concrete in the future to improve the corrosion resistance of concrete. At the same time, the limitations and challenges are also pointed out.

Accurate and continuous respiratory rate using touchless monitoring technology.

PURPOSE: Respiratory rate is a commonly used vital sign with various clinical applications. It serves as a crucial marker of acute health issues and any significant alteration in respiratory rate may be an early warning sign of major issues such as infections in the respiratory tract, respiratory failure, or cardiac arrest. Timely recognition of changes in respiratory rate enables prompt medical action, while neglecting to detect a change may lead to adverse patient outcomes. Here, we report on the performance of respiratory rate determined using a depth sensing camera system (RRdepth) which allows for continuous, non-contact 'touchless' monitoring of this important vital sign. METHODS: Thirty adult volunteers undertook a range of set breathing rates to cover a target breathing range of 4-40 breaths/min. Depth information was acquired from the torso region of the subjects using an Intel D415 RealSense camera positioned above the bed. The depth information was processed to generate a respiratory signal from which RRdepth was calculated. This was compared to a manually scored capnograph reference (RRcap). RESULTS: An overall RMSD accuracy of 0.77 breaths/min was achieved across the target respiratory rate range with a corresponding bias of 0.05 breaths/min. This corresponded to a line of best fit given by RRdepth = 1.01 x RRcap - 0.22 breaths/min with an associated high degree of correlation (R = 0.997). A breakdown of the performance with respect to sub-ranges corresponding to respiratory rates or ≤7, >7-10, >10-20, >20-30, >30 breaths/min all exhibited RMSD accuracies of less than 1.00 breaths/min. We also had the opportunity to test the performance of spontaneous breathing of the subjects which occurred during the study and found an overall RMSD accuracy of 1.20 breaths/min with corresponding accuracies ≤1.30 breaths/min across each of the individual sub-ranges. CONCLUSIONS: We have conducted an investigative study of a prototype depth sensing camera system for the non-contact monitoring of respiratory rate. The system achieved good performance with high accuracy across a wide range of rates including both clinically important high and low rates.

The Roles of hnRNP Family in the Brain and Brain-Related Disorders.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) belong to a complex family of RNA-binding proteins that are essential to control alternative splicing, mRNA trafficking, synaptic plasticity, stress granule formation, cell cycle regulation, and axonal transport. Over the past decade, hnRNPs have been associated with different brain disorders such as Alzheimer's disease, multiple sclerosis, and schizophrenia. Given their essential role in maintaining cell function and integrity, it is not surprising that dysregulated hnRNP levels lead to neurological implications. This review aims to explore the primary functions of hnRNPs in neurons, oligodendrocytes, microglia, and astrocytes, and their roles in brain disorders. We also discuss proteomics and other technologies and their potential for studying and evaluating hnRNPs in brain disorders, including the discovery of new therapeutic targets and possible pharmacological interventions.

Climate determines transmission hotspots of Polycystic Echinococcosis, a life-threatening zoonotic disease, across Pan-Amazonia.

Polycystic Echinococcosis (PE), a neglected life-threatening zoonotic disease caused by the cestode Echinococcus vogeli, is endemic in the Amazon. Despite being treatable, PE reaches a case fatality rate of around 29% due to late or missed diagnosis. PE is sustained in Pan-Amazonia by a complex sylvatic cycle. The hunting of its infected intermediate hosts (especially the lowland paca Cuniculus paca) enables the disease to further transmit to humans, when their viscera are improperly handled. In this study, we compiled a unique dataset of host occurrences (~86000 records) and disease infections (~400 cases) covering the entire Pan-Amazonia and employed different modeling and statistical tools to unveil the spatial distribution of PE's key animal hosts. Subsequently, we derived a set of ecological, environmental, climatic, and hunting covariates that potentially act as transmission risk factors and used them as predictors of two independent Maximum Entropy models, one for animal infections and one for human infections. Our findings indicate that temperature stability promotes the sylvatic circulation of the disease. Additionally, we show how El Niño-Southern Oscillation (ENSO) extreme events disrupt hunting patterns throughout Pan-Amazonia, ultimately affecting the probability of spillover. In a scenario where climate extremes are projected to intensify, climate change at regional level appears to be indirectly driving the spillover of E. vogeli. These results hold substantial implications for a wide range of zoonoses acquired at the wildlife-human interface for which transmission is related to the manipulation and consumption of wild meat, underscoring the pressing need for enhanced awareness and intervention strategies.

Single-Cell RNA Sequencing and Its Applications in the Study of Psychiatric Disorders.

Neuroscience is currently one of the most challenging research fields owing to the enormous complexity of the mammalian nervous system. We are yet to understand precise transcriptional programs that govern cell fate during neurodevelopment, resolve the connectome of the mammalian brain, and determine the etiology of various neurodegenerative and psychiatric disorders. Technological advances in the past decade, notably single-cell RNA sequencing, have enabled huge progress in our understanding of such features. Our current knowledge of the transcriptome is largely derived from bulk RNA sequencing, which reveals only the average gene expression of millions of cells, potentially missing out on minor transcriptome differences between cells detectable only at single-cell resolution. Since 2009, several single-cell RNA sequencing techniques have emerged that enable the accurate classification of neuronal and glial cell subtypes beyond classical molecular markers and electrophysiological features and allow the identification of previously unknown cell types. Furthermore, it enables the interrogation of molecular and disease-relevant mechanisms and offers further possibilities for the discovery of new drug targets and disease biomarkers. This review intends to familiarize the reader with the main single-cell RNA sequencing techniques developed throughout the past decade and discusses their application in the fields of brain cell taxonomy, neurodevelopment, and psychiatric disorders.

Spectroscopic and Biophysical Methods to Determine Differential Salt-Uptake by Primitive Membraneless Polyester Microdroplets.

α-Hydroxy acids are prebiotic monomers that undergo dehydration synthesis to form polyester gels, which assemble into membraneless microdroplets upon aqueous rehydration. These microdroplets are proposed as protocells that can segregate and compartmentalize primitive molecules/reactions. Different primitive aqueous environments with a variety of salts could have hosted chemistries that formed polyester microdroplets. These salts could be essential cofactors of compartmentalized prebiotic reactions or even directly affect protocell structure. However, fully understanding polyester-salt interactions remains elusive, partially due to technical challenges of quantitative measurements in condensed phases. Here, spectroscopic and biophysical methods are applied to analyze salt uptake by polyester microdroplets. Inductively coupled plasma mass spectrometry is applied to measure the cation concentration within polyester microdroplets after addition of chloride salts. Combined with methods to determine the effects of salt uptake on droplet turbidity, size, surface potential and internal water distribution, it was observed that polyester microdroplets can selectively partition salt cations, leading to differential microdroplet coalescence due to ionic screening effects reducing electrostatic repulsion forces between microdroplets. Through applying existing techniques to novel analyses related to primitive compartment chemistry and biophysics, this study suggests that even minor differences in analyte uptake can lead to significant protocellular structural change.

Robust Non-Contact Monitoring of Respiratory Rate using a Depth Camera.

PURPOSE: Respiratory rate (RR) is one of the most common vital signs with numerous clinical uses. It is an important indicator of acute illness and a significant change in RR is often an early indication of a potentially serious complication or clinical event such as respiratory tract infection, respiratory failure and cardiac arrest. Early identification of changes in RR allows for prompt intervention, whereas failing to detect a change may result in poor patient outcomes. Here, we report on the performance of a depth-sensing camera system for the continuous non-contact 'touchless' monitoring of Respiratory Rate. METHODS: Seven healthy subjects undertook a range of breathing rates from 4 to 40 breaths-per-minute (breaths/min). These were set rates of 4, 5, 6, 8, 10, 15, 20, 25, 30, 35 and 40 breaths/min. In total, 553 separate respiratory rate recordings were captured across a range of conditions including body posture, position within the bed, lighting levels and bed coverings. Depth information was acquired from the scene using an Intel D415 RealSenseTM camera. This data was processed in real-time to extract depth changes within the subject's torso region corresponding to respiratory activity. A respiratory rate RRdepth was calculated using our latest algorithm and output once-per-second from the device and compared to a reference. RESULTS: An overall RMSD accuracy of 0.69 breaths/min with a corresponding bias of -0.034 was achieved across the target RR range of 4-40 breaths/min. Bland-Altman analysis revealed limits of agreement of -1.42 to 1.36 breaths/min. Three separate sub-ranges of low, normal and high rates, corresponding to < 12, 12-20, > 20 breaths/min, were also examined separately and each found to demonstrate RMSD accuracies of less than one breath-per-minute. CONCLUSIONS: We have demonstrated high accuracy in performance for respiratory rate based on a depth camera system. We have shown the ability to perform well at both high and low rates which are clinically important.

Hyperparameter Optimization of a Convolutional Neural Network Model for Pipe Burst Location in Water Distribution Networks.

The current paper presents a hyper parameterization optimization process for a convolutional neural network (CNN) applied to pipe burst locations in water distribution networks (WDN). The hyper parameterization process of the CNN includes the early stopping termination criteria, dataset size, dataset normalization, training set batch size, optimizer learning rate regularization, and model structure. The study was applied using a case study of a real WDN. Obtained results indicate that the ideal model parameters consist of a CNN with a convolutional 1D layer (using 32 filters, a kernel size of 3 and strides equal to 1) for a maximum of 5000 epochs using a total of 250 datasets (using data normalization between 0 and 1 and tolerance equal to max noise) and a batch size of 500 samples per epoch step, optimized with Adam using learning rate regularization. This model was evaluated for distinct measurement noise levels and pipe burst locations. Results indicate that the parameterized model can provide a pipe burst search area with more or less dispersion depending on both the proximity of pressure sensors to the burst or the noise measurement level.

Culturomics- and metagenomics-based insights into the microbial community and function of rhizosphere soils in Sinai desert farming systems.

BACKGROUND: The microbiome of the Sinai Desert farming system plays an important role in the adaptive strategy of growing crops in a harsh, poly-extreme, desert environment. However, the diversity and function of microbial communities under this unfavorable moisture and nutritional conditions have not yet been investigated. Based on culturomic and metagenomic methods, we analyzed the microbial diversity and function of a total of fourteen rhizosphere soil samples (collected from twelve plants in four farms of the Sinai desert), which may provide a valuable and meaningful guidance for the design of microbial inoculants. RESULTS: The results revealed a wide range of microbial taxa, including a high proportion of novel undescribed lineages. The composition of the rhizosphere microbial communities differed according to the sampling sites, despite similarities or differences in floristics. Whereas, the functional features of rhizosphere microbiomes were significantly similar in different sampling sites, although the microbial communities and the plant hosts themselves were different. Importantly, microorganisms involved in ecosystem functions are different between the sampling sites, for example nitrogen fixation was prevalent in all sample sites while microorganisms responsible for this process were different. CONCLUSION: Here, we provide the first characterization of microbial communities and functions of rhizosphere soil from the Sinai desert farming systems and highlight its unexpectedly high diversity. This study provides evidence that the key microorganisms involved in ecosystem functions are different between sampling sites with different environment conditions, emphasizing the importance of the functional microbiomes of rhizosphere microbial communities. Furthermore, we suggest that microbial inoculants to be used in future agricultural production should select microorganisms that can be involved in plant-microorganism interactions and are already adapted to a similar environmental setting.

Large-scale population disappearances and cycling in the white-lipped peccary, a tropical forest mammal.

Many vertebrate species undergo population fluctuations that may be random or regularly cyclic in nature. Vertebrate population cycles in northern latitudes are driven by both endogenous and exogenous factors. Suggested causes of mysterious disappearances documented for populations of the Neotropical, herd-forming, white-lipped peccary (Tayassu pecari, henceforth "WLP") include large-scale movements, overhunting, extreme floods, or disease outbreaks. By analyzing 43 disappearance events across the Neotropics and 88 years of commercial and subsistence harvest data for the Amazon, we show that WLP disappearances are widespread and occur regularly and at large spatiotemporal scales throughout the species' range. We present evidence that the disappearances represent 7-12-year troughs in 20-30-year WLP population cycles occurring synchronously at regional and perhaps continent-wide spatial scales as large as 10,000-5 million km2. This may represent the first documented case of natural population cyclicity in a Neotropical mammal. Because WLP populations often increase dramatically prior to a disappearance, we posit that their population cycles result from over-compensatory, density-dependent mortality. Our data also suggest that the increase phase of a WLP cycle is partly dependent on recolonization from proximal, unfragmented and undisturbed forests. This highlights the importance of very large, continuous natural areas that enable source-sink population dynamics and ensure re-colonization and local population persistence in time and space.

The archaeal class Halobacteria and astrobiology: Knowledge gaps and research opportunities.

Water bodies on Mars and the icy moons of the outer solar system are now recognized as likely being associated with high levels of salt. Therefore, the study of high salinity environments and their inhabitants has become increasingly relevant for Astrobiology. Members of the archaeal class Halobacteria are the most successful microbial group living in hypersaline conditions and are recognized as key model organisms for exposure experiments. Despite this, data for the class is uneven across taxa and widely dispersed across the literature, which has made it difficult to properly assess the potential for species of Halobacteria to survive under the polyextreme conditions found beyond Earth. Here we provide an overview of published data on astrobiology-linked exposure experiments performed with members of the Halobacteria, identifying clear knowledge gaps and research opportunities.

Impact of Microbiota Depletion by Antibiotics on SARS-CoV-2 Infection of K18-hACE2 Mice.

Clinical and experimental data indicate that severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection is associated with significant changes in the composition and function of intestinal microbiota. However, the relevance of these effects for SARS-CoV-2 pathophysiology is unknown. In this study, we analyzed the impact of microbiota depletion after antibiotic treatment on the clinical and immunological responses of K18-hACE2 mice to SARS-CoV-2 infection. Mice were treated with a combination of antibiotics (kanamycin, gentamicin, metronidazole, vancomycin, and colistin, Abx) for 3 days, and 24 h later, they were infected with SARS-CoV-2 B lineage. Here, we show that more than 80% of mice succumbed to infection by day 11 post-infection. Treatment with Abx had no impact on mortality. However, Abx-treated mice presented better clinical symptoms, with similar weight loss between infected-treated and non-treated groups. We observed no differences in lung and colon histopathological scores or lung, colon, heart, brain and kidney viral load between groups on day 5 of infection. Despite some minor differences in the expression of antiviral and inflammatory markers in the lungs and colon, no robust change was observed in Abx-treated mice. Together, these findings indicate that microbiota depletion has no impact on SARS-CoV-2 infection in mice.

Morphological, cellular, and molecular basis of brain infection in COVID-19 patients.

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.