Introducing the Bacterial and Viral Bioinformatics Resource Center (BV-BRC): a resource combining PATRIC, IRD and ViPR.

The National Institute of Allergy and Infectious Diseases (NIAID) established the Bioinformatics Resource Center (BRC) program to assist researchers with analyzing the growing body of genome sequence and other omics-related data. In this report, we describe the merger of the PAThosystems Resource Integration Center (PATRIC), the Influenza Research Database (IRD) and the Virus Pathogen Database and Analysis Resource (ViPR) BRCs to form the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) https://www.bv-brc.org/. The combined BV-BRC leverages the functionality of the bacterial and viral resources to provide a unified data model, enhanced web-based visualization and analysis tools, bioinformatics services, and a powerful suite of command line tools that benefit the bacterial and viral research communities.

Microbiome composition modulates secondary metabolism in a multispecies bacterial community.

Bacterial secondary metabolites are a major source of antibiotics and other bioactive compounds. In microbial communities, these molecules can mediate interspecies interactions and responses to environmental change. Despite the importance of secondary metabolites in human health and microbial ecology, little is known about their roles and regulation in the context of multispecies communities. In a simplified model of the rhizosphere composed of Bacillus cereus, Flavobacterium johnsoniae, and Pseudomonas koreensis, we show that the dynamics of secondary metabolism depend on community species composition and interspecies interactions. Comparative metatranscriptomics and metametabolomics reveal that the abundance of transcripts of biosynthetic gene clusters (BGCs) and metabolomic molecular features differ between monocultures or dual cultures and a tripartite community. In both two- and three-member cocultures, P. koreensis modified expression of BGCs for zwittermicin, petrobactin, and other secondary metabolites in B. cereus and F. johnsoniae, whereas the BGC transcriptional response to the community in P. koreensis itself was minimal. Pairwise and tripartite cocultures with P. koreensis displayed unique molecular features that appear to be derivatives of lokisin, suggesting metabolic handoffs between species. Deleting the BGC for koreenceine, another P. koreensis metabolite, altered transcript and metabolite profiles across the community, including substantial up-regulation of the petrobactin and bacillibactin BGCs in B. cereus, suggesting that koreenceine represses siderophore production. Results from this model community show that bacterial BGC expression and chemical output depend on the identity and biosynthetic capacity of coculture partners, suggesting community composition and microbiome interactions may shape the regulation of secondary metabolism in nature.

Small Intestinal Perforation after 360-Degree Liposuction: A Case Report.

OBJECTIVE: As one of the most commonly performed cosmetic procedures, liposuction is relatively safe. Bowel injury following liposuction is a rare but devastating complication, which necessitates hospital admission and surgical intervention. The authors highlight a case report describing the presentation, diagnosis, and management of a patient with bowel injury following liposuction. CASE: A 58-year-old woman presented with abdominal pain, erythema, and discharge three days after 360-degree abdominal liposuction with concomitant fat grafting to bilateral buttocks at an outpatient surgery center. Bowel perforation was suspected after CT-scan revealed extraluminal gas in the abdomen and communication that traversed the peritoneum. Exploratory laparotomy was performed which demonstrated at least one site of distinct perforation of the small bowel and an area omentum noted to be inflamed, thickened and with a purulent rind. The patient underwent 20-cm small bowel resection and partial omentectomy temporarily closed with negative pressure wound therapy. After subsequent abdominal wall debridements the patient received ventral hernia repair with bridging mesh and abdominal closure. CONCLUSIONS: While safe, elective cosmetic procedures are not without risk of serious and even fatal complications. Providers must be familiar with the presentation of bowel injury following abdominal liposuction to prevent delays in appropriate surgical and medical care. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease.

OBJECTIVE: This study aimed to assess whether non-invasive brain stimulation with transcranial alternating current stimulation at gamma-frequency (γ-tACS) applied over the precuneus can improve episodic memory and modulate cholinergic transmission by modulating cerebral rhythms in early Alzheimer's disease (AD). METHODS: In this randomized, double-blind, sham controlled, crossover study, 60 AD patients underwent a clinical and neurophysiological evaluation including assessment of episodic memory and cholinergic transmission pre and post 60 minutes treatment with γ-tACS targeting the precuneus or sham tACS. In a subset of 10 patients, EEG analysis and individualized modelling of electric field distribution were carried out. Predictors to γ-tACS efficacy were evaluated. RESULTS: We observed a significant improvement in the Rey Auditory Verbal Learning (RAVL) test immediate recall (p < 0.001) and delayed recall scores (p < 0.001) after γ-tACS but not after sham tACS. Face-name associations scores improved with γ-tACS (p < 0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission, increased only after γ-tACS (p < 0.001). ApoE genotype and baseline cognitive impairment were the best predictors of response to γ-tACS. Clinical improvement correlated with the increase in gamma frequencies in posterior regions and with the amount of predicted electric field distribution in the precuneus. INTERPRETATION: Precuneus γ-tACS, able to increase γ-power activity on the posterior brain regions, showed a significant improvement of episodic memory performances, along with restoration of intracortical excitability measures of cholinergic transmission. Response to γ-tACS was dependent on genetic factors and disease stage. ANN NEUROL 2022;92:322-334.

Biodiversity change under adaptive community dynamics.

Compositional change is a ubiquitous response of ecological communities to environmental drivers of global change, but is often regarded as evidence of declining "biotic integrity" relative to historical baselines. Adaptive compositional change, however, is a foundational idea in evolutionary biology, whereby changes in gene frequencies within species boost population-level fitness, allowing populations to persist as the environment changes. Here, we present an analogous idea for ecological communities based on core concepts of fitness and selection. Changes in community composition (i.e., frequencies of genetic differences among species) in response to environmental change should normally increase the average fitnessof community members. We refer to compositional changes that improve the functional match, or "fit," between organisms' traits and their environment as adaptive community dynamics. Environmental change (e.g., land-use change) commonly reduces the fit between antecedent communities and new environments. Subsequent change in community composition in response to environmental changes, however, should normally increase community-level fit, as the success of at least some constituent species increases. We argue that adaptive community dynamics are likely to improve or maintain ecosystem function (e.g., by maintaining productivity). Adaptive community responses may simultaneously produce some changes that are considered societally desirable (e.g., increased carbon storage) and others that are undesirable (e.g., declines of certain species), just as evolutionary responses within species may be deemed desirable (e.g., evolutionary rescue of an endangered species) or undesirable (e.g., enhanced virulence of an agricultural pest). When assessing possible management interventions, it is important to distinguish between drivers of environmental change (e.g., undesired climate warming) and adaptive community responses, which may generate some desirable outcomes. Efforts to facilitate, accept, or resist ecological change require separate consideration of drivers and responses, and may highlight the need to reconsider preferences for historical baseline communities over communities that are better adapted to the new conditions.

Increased dispersal explains increasing local diversity with global biodiversity declines.

The narrative of biodiversity decline in response to human impacts is overly simplistic because different aspects of biodiversity show different trajectories at different spatial scales. It is also debated whether human-caused biodiversity changes lead to subsequent, accelerating change (cascades) in ecological communities, or alternatively build increasingly robust community networks with decreasing extinction rates and reduced invasibility. Mechanistic approaches are needed that simultaneously reconcile different aspects of biodiversity change, and explore the robustness of communities to further change. We develop a trophically structured, mainland-archipelago metacommunity model of community assembly. Varying the parameters across model simulations shows that local alpha diversity (the number of species per island) and regional gamma diversity (the total number of species in the archipelago) depend on both the rate of extirpation per island and on the rate of dispersal between islands within the archipelago. In particular, local diversity increases with increased dispersal and heterogeneity between islands, but regional diversity declines because the islands become biotically similar and local one-island and few-island species are excluded (homogenisation, or reduced beta diversity). This mirrors changes observed empirically: real islands have gained species (increased local and island-scale community diversity) with increased human-assisted transfers of species, but global diversity has declined with the loss of endemic species. However, biological invasions may be self-limiting. High-dispersal, high local-diversity model communities become resistant to subsequent invasions, generating robust species-community networks unless dispersal is extremely high. A mixed-up world is likely to lose many species, but the resulting ecological communities may nonetheless be relatively robust.

Impacts of seasonal flooding on geographical access to maternal healthcare in the Barotse Floodplain, Zambia.

BACKGROUND: Seasonal floods pose a commonly-recognised barrier to women's access to maternal services, resulting in increased morbidity and mortality. Despite their importance, previous GIS models of healthcare access have not adequately accounted for floods. This study developed new methodologies for incorporating flood depths, velocities, and extents produced with a flood model into network- and raster-based health access models. The methodologies were applied to the Barotse Floodplain to assess flood impact on women's walking access to maternal services and vehicular emergency referrals for a monthly basis between October 2017 and October 2018. METHODS: Information on health facilities were acquired from the Ministry of Health. Population density data on women of reproductive age were obtained from the High Resolution Settlement Layer. Roads were a fusion of OpenStreetMap and data manually delineated from satellite imagery. Monthly information on floodwater depth and velocity were obtained from a flood model for 13-months. Referral driving times between delivery sites and EmOC were calculated with network analysis. Walking times to the nearest maternal services were calculated using a cost-distance algorithm. RESULTS: The changing distribution of floodwaters impacted the ability of women to reach maternal services. At the peak of the dry season (October 2017), 55%, 19%, and 24% of women had walking access within 2-hrs to their nearest delivery site, EmOC location, and maternity waiting shelter (MWS) respectively. By the flood peak, this dropped to 29%, 14%, and 16%. Complete inaccessibility became stark with 65%, 76%, and 74% unable to access any delivery site, EmOC, and MWS respectively. The percentage of women that could be referred by vehicle to EmOC from a delivery site within an hour also declined from 65% in October 2017 to 23% in March 2018. CONCLUSIONS: Flooding greatly impacted health access, with impacts varying monthly as the floodwave progressed. Additional validation and application to other regions is still needed, however our first results suggest the use of a hydrodynamic model permits a more detailed representation of floodwater impact and there is great potential for generating predictive models which will be necessary to consider climate change impacts on future health access.

A Multicenter, Prospective, Observational, Cohort-Controlled Study of Clinical Outcomes Following Coronavirus Disease 2019 (COVID-19) Convalescent Plasma Therapy in Hospitalized Patients With COVID-19.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high inpatient mortality and morbidity throughout the world. COVID-19 convalescent plasma (CCP) has been utilized as a potential therapy for patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. This study evaluated the outcomes of hospitalized patients with COVID-19 treated with CCP in a prospective, observational, multicenter trial. METHODS: From April through August 2020, hospitalized patients with COVID-19 at 16 participating hospitals in Colorado were enrolled and treated with CCP and compared with hospitalized patients with COVID-19 who were not treated with convalescent plasma. Plasma antibody levels were determined following the trial, given that antibody tests were not approved at the initiation of the trial. CCP-treated and untreated hospitalized patients with COVID-19 were matched using propensity scores followed by analysis for length of hospitalization and inpatient mortality. RESULTS: A total of 542 hospitalized patients with COVID-19 were enrolled at 16 hospitals across the region. A total of 468 hospitalized patients with COVID-19 were entered into propensity score matching with 188 patients matched for analysis in the CCP-treatment and control arms. Fine-Gray models revealed increased length of hospital stay in CCP-treated patients and no change in inpatient mortality compared with controls. In subgroup analysis of CCP-treated patients within 7 days of admission, there was no difference in length of hospitalization and inpatient mortality. CONCLUSIONS: These data show that treatment of hospitalized patients with COVID-19 treated with CCP did not significantly improve patient hospitalization length of stay or inpatient mortality.

Lost, gained, and regained functional and phylogenetic diversity of European mammals since 8000 years ago.

Mammals have experienced high levels of human-mediated extirpations but have also been widely introduced to new locations, and some have recovered from historic persecution. Both of these processes-losses and gains-have resulted in concern about functional losses and changes in ecological communities as new ecological states develop. The question of whether species turnover inevitably leads to declines in functional and phylogenetic diversity depends, however, on the traits and phylogenetic distinctiveness of the species that are lost, gained, or regained. Comparing ~8000 years ago with the last century, we show that extirpations and range retractions have indeed reduced the functional and phylogenetic diversity of mammals in most European regions (countries and island groups), but species recoveries and the introduction of non-native species have increased functional and phylogenetic diversity by equivalent or greater amounts in many regions. Overall, across Europe, species richness increased in 41 regions over the last 8000 years and declined in 1; phylogenetic diversity increased in 33 and declined in 12, while functional diversity results showed 20 increases and 25 decreases. The balance of losses (extirpations) and gains (introductions, range expansions) has, however, led to net increases in functional diversity on many islands, where the original diversity was low, and across most of western Europe. Historically extirpated mega- and mesofaunal species have recolonized or been reintroduced to many European regions, contributing to recent functional and phylogenetic diversity recovery. If conservation rewilding projects continue to reintroduce regionally extirpated species and domestic descendants of "extinct" species to provide replacement grazing, browsing, and predation, there is potential to generate net functional and phylogenetic diversity gains (relative to 8000 years ago) in most European regions.

A millennium of increasing diversity of ecosystems until the mid-20th century.

Land-use change is widely regarded as a simplifying and homogenising force in nature. In contrast, analysing global land-use reconstructions from the 10th to 20th centuries, we found progressive increases in the number, evenness, and diversity of ecosystems (including human-modified land-use types) present across most of the Earth's land surface. Ecosystem diversity increased more rapidly after ~1700 CE, then slowed or slightly declined (depending on the metric) following the mid-20th century acceleration of human impacts. The results also reveal increasing spatial differentiation, rather than homogenisation, in both the presence-absence and area-coverage of different ecosystem types at sub-global scales-at least, prior to the mid-20th century. Nonetheless, geographic homogenization was revealed for a subset of analyses at a global scale, reflecting the now-global presence of certain human-modified ecosystem types. Our results suggest that, while human land-use changes have caused declines in relatively undisturbed or "primary" ecosystem types, they have also driven increases in ecosystem diversity over the last millennium.

Community implications for gun violence prevention during co-occurring pandemics; a qualitative and computational analysis study.

This study provides insight into New York City residents' perceptions about violence after the outbreak of Coronavirus disease (COVID-19) based on information from communities in New York City Housing Authority (NYCHA) buildings. In this novel analysis, we used focus group and social media data to confirm or reject findings from qualitative interviews. We first used data from 69 in-depth, semi-structured interviews with low-income residents and community stakeholders to further explore how violence impacts New York City's low-income residents of color, as well as the role of city government in providing tangible support for violence prevention during co-occurring health (COVID-19) and social (anti-Black racism) pandemics. Residents described how COVID-19 and the Black Lives Matter movement impacted safety in their communities while offering direct recommendations to improve safety. Residents also shared recommendations that indirectly improve community safety by addressing long term systemic issues. As the recruitment of interviewees was concluding, researchers facilitated two focus groups with 38 interviewees to discuss similar topics. In order to assess the degree to which the themes discovered in our qualitative interviews were shared by the broader community, we developed an integrative community data science study which leveraged natural language processing and computer vision techniques to study text and images on public social media data of 12 million tweets generated by residents. We joined computational methods with qualitative analysis through a social work lens and design justice principles to most accurately and holistically analyze the community perceptions of gun violence issues and potential prevention strategies. Findings indicate valuable community-based insights that elucidate how the co-occurring pandemics impact residents' experiences of gun violence and provide important implications for gun violence prevention in a digital era.

Motor and cognitive outcomes of cerebello-spinal stimulation in neurodegenerative ataxia.

Cerebellar ataxias represent a heterogeneous group of disabling disorders characterized by motor and cognitive disturbances, for which no effective treatment is currently available. In this randomized, double-blind, sham-controlled trial, followed by an open-label phase, we investigated whether treatment with cerebello-spinal transcranial direct current stimulation (tDCS) could improve both motor and cognitive symptoms in patients with neurodegenerative ataxia at short and long-term. Sixty-one patients were randomized in two groups for the first controlled phase. At baseline (T0), Group 1 received placebo stimulation (sham tDCS) while Group 2 received anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5 days/week for 2 weeks (T1), with a 12-week (T2) follow-up (randomized, double-blind, sham controlled phase). At the 12-week follow-up (T2), all patients (Group 1 and Group 2) received a second treatment of anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5 days/week for 2 weeks, with a 14-week (T3), 24-week (T4), 36-week (T5) and 52-week follow-up (T6) (open-label phase). At each time point, a clinical, neuropsychological and neurophysiological evaluation was performed. Cerebellar-motor cortex connectivity was evaluated using transcranial magnetic stimulation. We observed a significant improvement in all motor scores (scale for the assessment and rating of ataxia, international cooperative ataxia rating scale), in cognition (evaluated with the cerebellar cognitive affective syndrome scale), in quality-of-life scores, in motor cortex excitability and in cerebellar inhibition after real tDCS compared to sham stimulation and compared to baseline (T0), both at short and long-term. We observed an addon-effect after two repeated treatments with real tDCS compared to a single treatment with real tDCS. The improvement at motor and cognitive scores correlated with the restoration of cerebellar inhibition evaluated with transcranial magnetic stimulation. Cerebello-spinal tDCS represents a promising therapeutic approach for both motor and cognitive symptoms in patients with neurodegenerative ataxia, a still orphan disorder of any pharmacological intervention.

The PATRIC Bioinformatics Resource Center: expanding data and analysis capabilities.

The PathoSystems Resource Integration Center (PATRIC) is the bacterial Bioinformatics Resource Center funded by the National Institute of Allergy and Infectious Diseases (https://www.patricbrc.org). PATRIC supports bioinformatic analyses of all bacteria with a special emphasis on pathogens, offering a rich comparative analysis environment that provides users with access to over 250 000 uniformly annotated and publicly available genomes with curated metadata. PATRIC offers web-based visualization and comparative analysis tools, a private workspace in which users can analyze their own data in the context of the public collections, services that streamline complex bioinformatic workflows and command-line tools for bulk data analysis. Over the past several years, as genomic and other omics-related experiments have become more cost-effective and widespread, we have observed considerable growth in the usage of and demand for easy-to-use, publicly available bioinformatic tools and services. Here we report the recent updates to the PATRIC resource, including new web-based comparative analysis tools, eight new services and the release of a command-line interface to access, query and analyze data.

Comparison of Transcranial Focused Ultrasound and Transcranial Pulse Stimulation for Neuromodulation: A Computational Study.

OBJECTIVE: The objective of the study was to investigate transcranial wave propagation through two low-intensity focused ultrasound (LIFU)-based brain stimulation techniques-transcranial focused ultrasound stimulation (tFUS) and transcranial pulse stimulation (TPS). Although tFUS involves delivering long trains of acoustic pulses, the newly introduced TPS delivers ultrashort (∼3 µs) pulses repeated at 4 Hz. Accordingly, only a single simulation study with limited geometry currently exists for TPS. We considered a high-resolution three-dimensional (3D) whole human head model in addition to water bath simulations. We anticipate that the results of this study will help researchers investigating LIFU have a better understanding of the effects of the two different techniques. APPROACH: With an objective to first reproduce previous computational results, we considered two spherical tFUS transducers that were previously modeled. We assumed identical parameters (geometry, position, and imaging data set) to demonstrate differences, purely because of the waveform considered. For simulations with a 3D head data set, we also considered a parabolic transducer that has been used for TPS delivery. RESULTS: Our initial results successfully verified previous modeling workflow. The tFUS distribution was characterized by the typical elliptical profile, with its major axis perpendicular to the face of the transducer. The TPS distribution resembled two mirrored meniscus profiles, with its widest diameter oriented parallel to the face of the transducer. The observed intensity value differences were theoretical because the two waveforms differ in both intensity and time. The consideration of a realistic 3D human head model resulted in only a minor distortion of the two waveforms. SIGNIFICANCE: This study simulated TPS administration using a 3D realistic image-derived data set. Although our comparison results are strictly limited to the model parameters and assumptions made, we were able to elucidate some clear differences between the two approaches. We hope this initial study will pave the way for systematic comparison between the two approaches in the future.

An exploration of factors characterising unusual spatial clusters of COVID-19 cases in the East Midlands region, UK: A geospatial analysis of ambulance 999 data.

Complex interactions between physical landscapes and social factors increase vulnerability to emerging infections and their sequelae. Relative vulnerability to severe illness and/or death (VSID) depends on risk and extent of exposure to a virus and underlying health susceptibility. Identifying vulnerable communities and the regions they inhabit in real time is essential for effective rapid response to a new pandemic, such as COVID-19. In the period between first confirmed cases and the introduction of widespread community testing, ambulance records of suspected severe illness from COVID-19 could be used to identify vulnerable communities and regions and rapidly appraise factors that may explain VSID. We analyse the spatial distribution of more than 10,000 suspected severe COVID-19 cases using records of provisional diagnoses made by trained paramedics attending medical emergencies. We identify 13 clusters of severe illness likely related to COVID-19 occurring in the East Midlands of the UK and present an in-depth analysis of those clusters, including urban and rural dynamics, the physical characteristics of landscapes, and socio-economic conditions. Our findings suggest that the dynamics of VSID vary depending on wider geographic location. Vulnerable communities and regions occur in more deprived urban centres as well as more affluent peri-urban and rural areas. This methodology could contribute to the development of a rapid national response to support vulnerable communities during emerging pandemics in real time to save lives.

Early prediction of post-molar gestational trophoblastic neoplasia and resistance to methotrexate, based on a single serum human chorionic gonadotropin measurement.

BACKGROUND: Clinicians are unable to provide individualized counseling regarding risk of progression for patients with a complete hydatidiform mole (CHM). We developed nomograms enabling early prediction of post-molar gestational trophoblastic neoplasia (GTN) and resistance to methotrexate (MTX) based on a single serum human chorion gonadotropin (hCG) measurement. METHODS: We generated two nomograms with logistic regression: to predict post-molar GTN, and MTX resistance. For patients with high probability to progress to post-molar GTN or MTX resistance, we determined hCG cut-offs at 97.5% specificity to select patients for additional- or adjustments in current treatment. RESULTS: The nomograms had a good to excellent ability to distinguish either between patients with uneventful hCG regression versus progression to post molar GTN, or between patients cured by MTX versus patients in whom resistance would occur. At 97.5% specificity, we identified 66% (95%CI 56-75) of the 149 patients who would progress to post-molar GTN, four weeks after initial curettage. For patients treated with MTX, we identified 55% (95%CI 23-83) of the 43 patients who would become resistant, preceding their third course at 97.5% specificity. CONCLUSION: The nomograms and cut-off levels can be used to assist in counseling for patients diagnosed with CHM.

Introduced plants as novel Anthropocene habitats for insects.

Major environmental changes in the history of life on Earth have given rise to novel habitats, which gradually accumulate species. Human-induced change is no exception, yet the rules governing species accumulation in anthropogenic habitats are not fully developed. Here we propose that nonnative plants introduced to Great Britain may function as analogues of novel anthropogenic habitats for insects and mites, analysing a combination of local-scale experimental plot data and geographic-scale data contained within the Great Britain Database of Insects and their Food Plants. We find that novel plant habitats accumulate the greatest diversity of insect taxa when they are widespread and show some resemblance to plant habitats which have been present historically (based on the relatedness between native and nonnative plant species), with insect generalists colonizing from a wider range of sources. Despite reduced per-plant diversity, nonnative plants can support distinctive insect communities, sometimes including insect taxa that are otherwise rare or absent. Thus, novel plant habitats may contribute to, and potentially maintain, broader-scale (assemblage) diversity in regions that contain mixtures of long-standing and novel plant habitats.

Pyridine-2,6-Dithiocarboxylic Acid and Its Metal Complexes: New Inhibitors of New Delhi Metallo ß-Lactamase-1.

Keywords: NDM-1 inhibitors; marine-derived Streptomyces sp.; carbapenem-resistant Enterobacteriaceae; metal chelators.

Synergistic and antagonistic effects of land use and non-native species on community responses to climate change.

Climate change, land-use change and introductions of non-native species are key determinants of biodiversity change worldwide. However, the extent to which anthropogenic drivers of environmental change interact to affect biological communities is largely unknown, especially over longer time periods. Here, we show that plant community composition in 996 Swedish landscapes has consistently shifted to reflect the warmer and wetter climate that the region has experienced during the second half of the 20th century. Using community climatic indices, which reflect the average climatic associations of the species within each landscape at each time period, we found that species compositions in 74% of landscapes now have a higher representation of warm-associated species than they did previously, while 84% of landscapes now host more species associated with higher levels of precipitation. In addition to a warmer and wetter climate, there have also been large shifts in land use across the region, while the fraction of non-native species has increased in the majority of landscapes. Climatic warming at the landscape level appeared to favour the colonization of warm-associated species, while also potentially driving losses in cool-associated species. However, the resulting increases in community thermal means were apparently buffered by landscape simplification (reduction in habitat heterogeneity within landscapes) in the form of increased forest cover. Increases in non-native species, which generally originate from warmer climates than Sweden, were a strong driver of community-level warming. In terms of precipitation, both landscape simplification and increases in non-natives appeared to favour species associated with drier climatic conditions, to some extent counteracting the climate-driven shift towards wetter communities. Anthropogenic drivers can act both synergistically and antagonistically to determine trajectories of change in biological communities over time. Therefore, it is important to consider multiple drivers of global change when trying to understand, manage and predict biodiversity in the future.