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Globally acclaimed architectural designer John Pawson takes you on a multi-colored journey across the world through a carefully curated sequence of 320 images, a celebration of color from one of the most unexpected sources. His architecture might be known for its limited color palette ? primarily white ? but his photographs tell another story. His work which includes the new Design Museum in London and Calvin Klein retail stores, takes photographs of patterns, details, and textures to inform his work.

The COVID-19 pandemic disrupted many aspects of academic research, particularly for early career investigators striving for independence. This study examines geographic heterogeneity in the pandemic’s impact on the publication productivity of recipients of National Heart, Lung, and Blood Institute K01, K08, and K23 awards within Departments of Medicine across different states in the US using data from the National Institutes of Health RePORTER and the Centers for Disease Control and Prevention COVID data tracker from 2015 to 2022. Findings indicate that while publication productivity increased steadily until 2020, it plateaued soon after. K-awardees in states with an early peak in COVID-19-related deaths maintained relatively stable productivity levels post-2020, whereas those in states with a late peak experienced a decline. The observed geographic differences may stem from variations in pandemic response measures, resource availability, and institutional support. These findings highlight the need for careful consideration of geographic heterogeneity when designing targeted interventions, such as funding support and tenure extensions, to mitigate the pandemic’s impact on early career investigators. Addressing additional factors, including career stage, personal responsibilities, and institutional environments, is essential for a comprehensive understanding of disparities in publication productivity.

Changing environmental conditions cause changes in the distributions of phenotypic traits in natural populations. However, determining the mechanisms responsible for these changes-and, in particular, the relative contributions of phenotypic plasticity versus evolutionary responses-is difficult. To our knowledge, no study has yet reported evidence that evolutionary change underlies the most widely reported phenotypic response to climate change: the advancement of breeding times. In a wild population of red deer, average parturition date has advanced by nearly 2 weeks in 4 decades. Here, we quantify the contribution of plastic, demographic, and genetic components to this change. In particular, we quantify the role of direct phenotypic plasticity in response to increasing temperatures and the role of changes in the population structure. Importantly, we show that adaptive evolution likely played a role in the shift towards earlier parturition dates. The observed rate of evolution was consistent with a response to selection and was less likely to be due to genetic drift. Our study provides a rare example of observed rates of genetic change being consistent with theoretical predictions, although the consistency would not have been detected with a solely phenotypic analysis. It also provides, to our knowledge, the first evidence of both evolution and phenotypic plasticity contributing to advances in phenology in a changing climate.

Results from 16S rDNA-encoding gene sequence-based, culture-independent techniques have led to conflicting conclusions about the composition of the lower respiratory tract microbiome. To compare the microbiome of the upper and lower respiratory tract in healthy HIV-uninfected nonsmokers and smokers in a multicenter cohort. Participants were nonsmokers and smokers without significant comorbidities. Oral washes and bronchoscopic alveolar lavages were collected in a standardized manner. Sequence analysis of bacterial 16S rRNA-encoding genes was performed, and the neutral model in community ecology was used to identify bacteria that were the most plausible members of a lung microbiome. Sixty-four participants were enrolled. Most bacteria identified in the lung were also in the mouth, but specific bacteria such as Enterobacteriaceae, Haemophilus, Methylobacterium, and Ralstonia species were disproportionally represented in the lungs compared with values predicted by the neutral model. Tropheryma was also in the lung, but not the mouth. Mouth communities differed between nonsmokers and smokers in species such as Porphyromonas, Neisseria, and Gemella, but lung bacterial populations did not. This study is the largest to examine composition of the lower respiratory tract microbiome in healthy individuals and the first to use the neutral model to compare the lung to the mouth. Specific bacteria appear in significantly higher abundance in the lungs than would be expected if they originated from the mouth, demonstrating that the lung microbiome does not derive entirely from the mouth. The mouth microbiome differs in nonsmokers and smokers, but lung communities were not significantly altered by smoking.

Background Due to recurrent hypoxia-reperfusion injury induced by vaso-occlusive crises (VOC), patients with sickle cell disease (SCD) may have intestinal injury and increased permeability. These may explain the qualitative and quantitative neutrophil abnormalities observed in these patients. Methods Serum intestinal fatty-acid binding protein (iFABP), lipopolysaccharides (LPS), and CD62L were measured by ELISA. Multicolor flow cytometry was used to measure circulating aged neutrophils. Results Compared to controls, SCD individuals had higher iFABP (median: 1.38 ng/ml vs 0.81 ng/ml; p  = 0.04) and LPS (median: 2.15 μg/ml vs 0.69 μg/ml; p  = 0.03), indicating intestinal injury and increased intestinal bacterial translocation into the systemic circulation. They also had higher soluble CD62L (median: 1.38 μg/ml vs 1.11 μg/ml; p  = 0.04). Among SCD individuals, soluble CD62L correlated positively with circulating aged neutrophils ( R  = 0.7, p  = 0.03) and LPS ( R  = 0.66, p  = 0.027). Surprisingly, serum iFABP in SCD correlated negatively with both LPS ( R  = − 0.7, p  = 0.02) and soluble CD62L ( R  = − 0.56, p  = 0.08). Conclusions Since LPS translocation across the intestinal barrier may be due to increases in the intestinal bacterial density, gut permeability, or both, the negative correlations between iFABP and LPS, and CD62L raise the possibility that any damage-associated molecular patterns induced by intestinal injury may modulate the degree of bacterial translocation. Our results provide the first evidence of the presence of intestinal injury and increased gut permeability in SCD.

Background No microbe exists in isolation, and few live in environments with only members of their own kingdom or domain. As microbiome studies become increasingly more interested in the interactions between microbes than in cataloging which microbes are present, the variety of microbes in the community should be considered. However, the majority of ecological interaction networks for microbiomes built to date have included only bacteria. Joint association inference across multiple domains of life, e.g., fungal communities (the mycobiome) and bacterial communities, has remained largely elusive. Results Here, we present a novel extension of the SParse InversE Covariance estimation for Ecological ASsociation Inference (SPIEC-EASI) framework that allows statistical inference of cross-domain associations from targeted amplicon sequencing data. For human lung and skin micro- and mycobiomes, we show that cross-domain networks exhibit higher connectivity, increased network stability, and similar topological re-organization patterns compared to single-domain networks. We also validate in vitro a small number of cross-domain interactions predicted by the skin association network. Conclusions For the human lung and skin micro- and mycobiomes, our findings suggest that fungi play a stabilizing role in ecological network organization. Our study suggests that computational efforts to infer association networks that include all forms of microbial life, paired with large-scale culture-based association validation experiments, will help formulate concrete hypotheses about the underlying biological mechanisms of species interactions and, ultimately, help understand microbial communities as a whole.

Background Metagenomic sequencing of respiratory microbial communities for pathogen identification in pneumonia may help overcome the limitations of culture-based methods. We examined the feasibility and clinical validity of rapid-turnaround metagenomics with Nanopore™ sequencing of clinical respiratory specimens. Methods We conducted a case-control study of mechanically-ventilated patients with pneumonia (nine culture-positive and five culture-negative) and without pneumonia (eight controls). We collected endotracheal aspirates and applied a microbial DNA enrichment method prior to metagenomic sequencing with the Oxford Nanopore MinION device. For reference, we compared Nanopore results against clinical microbiologic cultures and bacterial 16S rRNA gene sequencing. Results Human DNA depletion enabled in depth sequencing of microbial communities. In culture-positive cases, Nanopore revealed communities with high abundance of the bacterial or fungal species isolated by cultures. In four cases with resistant clinical isolates, Nanopore detected antibiotic resistance genes corresponding to the phenotypic resistance in antibiograms. In culture-negative pneumonia, Nanopore revealed probable bacterial pathogens in 1/5 cases and Candida colonization in 3/5 cases. In controls, Nanopore showed high abundance of oral bacteria in 5/8 subjects, and identified colonizing respiratory pathogens in other subjects. Nanopore and 16S sequencing showed excellent concordance for the most abundant bacterial taxa. Conclusions We demonstrated technical feasibility and proof-of-concept clinical validity of Nanopore metagenomics for severe pneumonia diagnosis, with striking concordance with positive microbiologic cultures, and clinically actionable information obtained from sequencing in culture-negative samples. Prospective studies with real-time metagenomics are warranted to examine the impact on antimicrobial decision-making and clinical outcomes.

Complex microbial communities within the human body, constituting the microbiome, have a broad impact on human health and disease. A growing body of research now examines the role of the microbiome in patients with critical illness, such as sepsis and acute respiratory failure. In this article, we provide an introduction to microbiome concepts and terminology and we systematically review the current evidence base of the critical-illness microbiome, including 51 studies in animal models and pediatric and adult critically ill patients. We further examine how this emerging scientific discipline may transform the way we manage infectious and inflammatory diseases in intensive care units. The evolving molecular, culture-independent techniques offer the ability to study microbial communities in unprecedented depth and detail, and in the short-term, may enable us to diagnose and treat infections in critical care more precisely and effectively. Longer term, these tools may also give us insights in the underlying pathophysiology of critical illness and reveal previously unsuspected targets for innovative, microbiome-targeted therapeutics. We finally propose a roadmap for future studies in the field for transforming critical care from its current isolated focus on the host to a more personalized paradigm addressing both human and microbial contributions to critical illness.

Background Men who have sex with men (MSM) have been disproportionately affected by HIV-1 since the beginning of the AIDS pandemic, particularly in the USA and Europe. Compared to men who have sex with women (MSW), MSM have a distinct fecal microbiome regardless of HIV-1 infection. However, it is unclear whether the MSM-associated gut microbiome affects the susceptibility and progression of HIV-1 infection. We studied fecal microbiome profiles, short-chain fatty acids, and blood plasma inflammatory cytokines of 109 HIV-1 seroconverters (SC) from the early, 1984–1985 phase of the HIV-1 pandemic in the Multicenter AIDS Cohort Study (MACS) before and after HIV-1 infection compared to 156 HIV-1-negative MACS MSM (negative controls [NC]). Results We found that family Succinivibrionaceae , S24-7, Mogibacteriaceae, Coriobacteriaceae , and Erysipelotrichaceae were significantly higher ( p <0.05), whereas Odoribacteraceae , Verucomicrobiaceae , Bacteroidaceae , Barnesiellaceae , and Rikenellaceae were significantly lower ( p <0.05), in SC before HIV-1 infection compared to NC. At the species level, Prevotella stercorea , Eubacterium biforme , and Collinsella aerofaciens were significantly higher ( p <0.05), and Eubacterium dolichum, Desulfovibrio D168, Alistipes onderdonkii, Ruminococcus torques , Bacteroides fragilis, Bacteroides caccae, Alistipes putredinis , Akkermansia muciniphila , Bacteroides uniformis , and Bacteroides ovatus were significantly lower ( p <0.05) in SC before HIV-1 infection compared to NC. After HIV-1 infection, family Prevotellaceae and Victivallaceae and species Bacteroides fragilis and Eubacterium cylindroides were significantly higher ( p <0.05) in SC who developed AIDS within 5 years compared to the SC who were AIDS free for more than 10 years without antiretroviral therapy (ART). In addition, family Victivallaceae and species Prevotella stercorea , Coprococcus eutactus , and Butyrivibrio crossotus were significantly higher ( p <0.05) and Gemmiger formicilis and Blautia obeum were significantly lower ( p <0.05) after HIV-1 infection in SC who developed AIDS within 5–10 years compared to the SC who were AIDS-free for more than 10 years without ART. Furthermore, plasma inflammatory cytokine levels of sCD14, sCD163, interleukin 6, and lipopolysaccharide binding protein were significantly higher in SC with p <0.05 before HIV-1 infection compared to NC. Conclusions Our results suggest that pathogenic changes in the gut microbiome were present in MSM several months prior to infection with HIV-1 in the early phase of the AIDS pandemic in the USA. This was associated with increased inflammatory biomarkers in the blood and risk for development of AIDS. 9QqqYi-nWWd_GoM3dpywa1 Video abstract

Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions. Here, the authors profile the oral, lung, and gut microbiota of 479 patients with acute respiratory failure, revealing that reduced diversity and increased pathogen presence can predict survival outcomes, highlighting the potential for microbiota-based approaches in critical care.