Biological Insight from Super-Resolution Microscopy: What We Can Learn from Localization-Based Images.

Super-resolution optical imaging based on the switching and localization of individual fluorescent molecules [photoactivated localization microscopy (PALM), stochastic optical reconstruction microscopy (STORM), etc.] has evolved remarkably over the last decade. Originally driven by pushing technological limits, it has become a tool of biological discovery. The initial demand for impressive pictures showing well-studied biological structures has been replaced by a need for quantitative, reliable data providing dependable evidence for specific unresolved biological hypotheses. In this review, we highlight applications that showcase this development, identify the features that led to their success, and discuss remaining challenges and difficulties. In this context, we consider the complex topic of defining resolution for this imaging modality and address some of the more common analytical methods used with this data.

Data Harmonization for a Molecularly Driven Health System.

Data commons have emerged as the best current method for enabling data aggregation across multiple projects and multiple data sources. Good data harmonization techniques are critical to maintain quality of data within a data commons, as well as to allow future meta-analysis across different data commons. We present some of the current best practices for data harmonization.

Systems Biology of Metabolism.

Metabolism is highly complex and involves thousands of different connected reactions; it is therefore necessary to use mathematical models for holistic studies. The use of mathematical models in biology is referred to as systems biology. In this review, the principles of systems biology are described, and two different types of mathematical models used for studying metabolism are discussed: kinetic models and genome-scale metabolic models. The use of different omics technologies, including transcriptomics, proteomics, metabolomics, and fluxomics, for studying metabolism is presented. Finally, the application of systems biology for analyzing global regulatory structures, engineering the metabolism of cell factories, and analyzing human diseases is discussed.

Cancer diagnosis and treatment in working-age adults: Implications for employment, health insurance coverage, and financial hardship in the United States.

The rising costs of cancer care and subsequent medical financial hardship for cancer survivors and families are well documented in the United States. Less attention has been paid to employment disruptions and loss of household income after a cancer diagnosis and during treatment, potentially resulting in lasting financial hardship, particularly for working-age adults not yet age-eligible for Medicare coverage and their families. In this article, the authors use a composite patient case to illustrate the adverse consequences of cancer diagnosis and treatment for employment, health insurance coverage, household income, and other aspects of financial hardship. They summarize existing research and provide nationally representative estimates of multiple aspects of financial hardship and health insurance coverage, benefit design, and employee benefits, such as paid sick leave, among working-age adults with a history of cancer and compare them with estimates among working-age adults without a history of cancer from the most recently available years of the National Health Interview Survey (2019-2021). Then, the authors identify opportunities for addressing employment and health insurance coverage challenges at multiple levels, including federal, state, and local policies; employers; cancer care delivery organizations; and nonprofit organizations. These efforts, when informed by research to identify best practices, can potentially help mitigate the financial hardship associated with cancer.

Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.

This article presents global cancer statistics by world region for the year 2022 based on updated estimates from the International Agency for Research on Cancer (IARC). There were close to 20 million new cases of cancer in the year 2022 (including nonmelanoma skin cancers [NMSCs]) alongside 9.7 million deaths from cancer (including NMSC). The estimates suggest that approximately one in five men or women develop cancer in a lifetime, whereas around one in nine men and one in 12 women die from it. Lung cancer was the most frequently diagnosed cancer in 2022, responsible for almost 2.5 million new cases, or one in eight cancers worldwide (12.4% of all cancers globally), followed by cancers of the female breast (11.6%), colorectum (9.6%), prostate (7.3%), and stomach (4.9%). Lung cancer was also the leading cause of cancer death, with an estimated 1.8 million deaths (18.7%), followed by colorectal (9.3%), liver (7.8%), female breast (6.9%), and stomach (6.8%) cancers. Breast cancer and lung cancer were the most frequent cancers in women and men, respectively (both cases and deaths). Incidence rates (including NMSC) varied from four-fold to five-fold across world regions, from over 500 in Australia/New Zealand (507.9 per 100,000) to under 100 in Western Africa (97.1 per 100,000) among men, and from over 400 in Australia/New Zealand (410.5 per 100,000) to close to 100 in South-Central Asia (103.3 per 100,000) among women. The authors examine the geographic variability across 20 world regions for the 10 leading cancer types, discussing recent trends, the underlying determinants, and the prospects for global cancer prevention and control. With demographics-based predictions indicating that the number of new cases of cancer will reach 35 million by 2050, investments in prevention, including the targeting of key risk factors for cancer (including smoking, overweight and obesity, and infection), could avert millions of future cancer diagnoses and save many lives worldwide, bringing huge economic as well as societal dividends to countries over the forthcoming decades.

Accelerated COVID-19 vaccine development: milestones, lessons, and prospects.

The development of effective vaccines to combat infectious diseases is a complex multi-year and multi-stakeholder process. To accelerate the development of vaccines for coronavirus disease 2019 (COVID-19), a novel pathogen emerging in late 2019 and spreading globally by early 2020, the United States government (USG) mounted an operation bridging public and private sector expertise and infrastructure. The success of the endeavor can be seen in the rapid advanced development of multiple vaccine candidates, with several demonstrating efficacy and now being administered around the globe. Here, we review the milestones enabling the USG-led effort, the methods utilized, and ensuing outcomes. We discuss the current status of COVID-19 vaccine development and provide a perspective for how partnership and preparedness can be better utilized in response to future public-health pandemic emergencies.

APOL1 risk variants in individuals of African genetic ancestry drive endothelial cell defects that exacerbate sepsis.

The incidence and severity of sepsis is higher among individuals of African versus European ancestry. We found that genetic risk variants (RVs) in the trypanolytic factor apolipoprotein L1 (APOL1), present only in individuals of African ancestry, were associated with increased sepsis incidence and severity. Serum APOL1 levels correlated with sepsis and COVID-19 severity, and single-cell sequencing in human kidneys revealed high expression of APOL1 in endothelial cells. Analysis of mice with endothelial-specific expression of RV APOL1 and in vitro studies demonstrated that RV APOL1 interfered with mitophagy, leading to cytosolic release of mitochondrial DNA and activation of the inflammasome (NLRP3) and the cytosolic nucleotide sensing pathways (STING). Genetic deletion or pharmacological inhibition of NLRP3 and STING protected mice from RV APOL1-induced permeability defects and proinflammatory endothelial changes in sepsis. Our studies identify the inflammasome and STING pathways as potential targets to reduce APOL1-associated health disparities in sepsis and COVID-19.

COVID-19 vaccine access in Africa: Global distribution, vaccine platforms, and challenges ahead.

Development COVID-19 vaccines in a record time has been an unprecedented global scientific achievement. However, the world has failed to ensure equitable access to what should have been a global public good. What options remain available to African countries to ensure immunization of their populations and ultimately overcome the pandemic?

Drought triggers and sustains overnight fires in North America.

Overnight fires are emerging in North America with previously unknown drivers and implications. This notable phenomenon challenges the traditional understanding of the 'active day, quiet night' model of the diurnal fire cycle1-3 and current fire management practices4,5. Here we demonstrate that drought conditions promote overnight burning, which is a key mechanism fostering large active fires. We examined the hourly diurnal cycle of 23,557 fires and identified 1,095 overnight burning events (OBEs, each defined as a night when a fire burned through the night) in North America during 2017-2020 using geostationary satellite data and terrestrial fire records. A total of 99% of OBEs were associated with large fires (>1,000 ha) and at least one OBE was identified in 20% of these large fires. OBEs were early onset after ignition and OBE frequency was positively correlated with fire size. Although warming is weakening the climatological barrier to night-time fires6, we found that the main driver of recent OBEs in large fires was the accumulated fuel dryness and availability (that is, drought conditions), which tended to lead to consecutive OBEs in a single wildfire for several days and even weeks. Critically, we show that daytime drought indicators can predict whether an OBE will occur the following night, which could facilitate early detection and management of night-time fires. We also observed increases in fire weather conditions conducive to OBEs over recent decades, suggesting an accelerated disruption of the diurnal fire cycle.

Online searches to evaluate misinformation can increase its perceived veracity.

Considerable scholarly attention has been paid to understanding belief in online misinformation1,2, with a particular focus on social networks. However, the dominant role of search engines in the information environment remains underexplored, even though the use of online search to evaluate the veracity of information is a central component of media literacy interventions3-5. Although conventional wisdom suggests that searching online when evaluating misinformation would reduce belief in it, there is little empirical evidence to evaluate this claim. Here, across five experiments, we present consistent evidence that online search to evaluate the truthfulness of false news articles actually increases the probability of believing them. To shed light on this relationship, we combine survey data with digital trace data collected using a custom browser extension. We find that the search effect is concentrated among individuals for whom search engines return lower-quality information. Our results indicate that those who search online to evaluate misinformation risk falling into data voids, or informational spaces in which there is corroborating evidence from low-quality sources. We also find consistent evidence that searching online to evaluate news increases belief in true news from low-quality sources, but inconsistent evidence that it increases belief in true news from mainstream sources. Our findings highlight the need for media literacy programmes to ground their recommendations in empirically tested strategies and for search engines to invest in solutions to the challenges identified here.

Evidence of human influence on Northern Hemisphere snow loss.

Documenting the rate, magnitude and causes of snow loss is essential to benchmark the pace of climate change and to manage the differential water security risks of snowpack declines1-4. So far, however, observational uncertainties in snow mass5,6 have made the detection and attribution of human-forced snow losses elusive, undermining societal preparedness. Here we show that human-caused warming has caused declines in Northern Hemisphere-scale March snowpack over the 1981-2020 period. Using an ensemble of snowpack reconstructions, we identify robust snow trends in 82 out of 169 major Northern Hemisphere river basins, 31 of which we can confidently attribute to human influence. Most crucially, we show a generalizable and highly nonlinear temperature sensitivity of snowpack, in which snow becomes marginally more sensitive to one degree Celsius of warming as climatological winter temperatures exceed minus eight degrees Celsius. Such nonlinearity explains the lack of widespread snow loss so far and augurs much sharper declines and water security risks in the most populous basins. Together, our results emphasize that human-forced snow losses and their water consequences are attributable-even absent their clear detection in individual snow products-and will accelerate and homogenize with near-term warming, posing risks to water resources in the absence of substantial climate mitigation.

Global shortfalls in documented actions to conserve biodiversity.

Threatened species are by definition species that are in need of assistance. In the absence of suitable conservation interventions, they are likely to disappear soon1. There is limited understanding of how and where conservation interventions are applied globally, or how well they work2,3. Here, using information from the International Union for Conservation of Nature Red List and other global databases, we find that for species at risk from three of the biggest drivers of biodiversity loss-habitat loss, overexploitation for international trade and invasive species4-many appear to lack the appropriate types of conservation interventions. Indeed, although there has been substantial recent expansion of the protected area network, we still find that 91% of threatened species have insufficient representation of their habitats within protected areas. Conservation interventions are not implemented uniformly across different taxa and regions and, even when present, have infrequently led to substantial improvements in the status of species. For 58% of the world's threatened terrestrial species, we find conservation interventions to be notably insufficient or absent. We cannot determine whether such species are truly neglected, or whether efforts to recover them are not included in major conservation databases. If they are indeed neglected, the outlook for many of the world's threatened species is grim without more and better targeted action.

Critical transitions in the Amazon forest system.

The possibility that the Amazon forest system could soon reach a tipping point, inducing large-scale collapse, has raised global concern1-3. For 65 million years, Amazonian forests remained relatively resilient to climatic variability. Now, the region is increasingly exposed to unprecedented stress from warming temperatures, extreme droughts, deforestation and fires, even in central and remote parts of the system1. Long existing feedbacks between the forest and environmental conditions are being replaced by novel feedbacks that modify ecosystem resilience, increasing the risk of critical transition. Here we analyse existing evidence for five major drivers of water stress on Amazonian forests, as well as potential critical thresholds of those drivers that, if crossed, could trigger local, regional or even biome-wide forest collapse. By combining spatial information on various disturbances, we estimate that by 2050, 10% to 47% of Amazonian forests will be exposed to compounding disturbances that may trigger unexpected ecosystem transitions and potentially exacerbate regional climate change. Using examples of disturbed forests across the Amazon, we identify the three most plausible ecosystem trajectories, involving different feedbacks and environmental conditions. We discuss how the inherent complexity of the Amazon adds uncertainty about future dynamics, but also reveals opportunities for action. Keeping the Amazon forest resilient in the Anthropocene will depend on a combination of local efforts to end deforestation and degradation and to expand restoration, with global efforts to stop greenhouse gas emissions.

Satellite mapping reveals extensive industrial activity at sea.

The world's population increasingly relies on the ocean for food, energy production and global trade1-3, yet human activities at sea are not well quantified4,5. We combine satellite imagery, vessel GPS data and deep-learning models to map industrial vessel activities and offshore energy infrastructure across the world's coastal waters from 2017 to 2021. We find that 72-76% of the world's industrial fishing vessels are not publicly tracked, with much of that fishing taking place around South Asia, Southeast Asia and Africa. We also find that 21-30% of transport and energy vessel activity is missing from public tracking systems. Globally, fishing decreased by 12 ± 1% at the onset of the COVID-19 pandemic in 2020 and had not recovered to pre-pandemic levels by 2021. By contrast, transport and energy vessel activities were relatively unaffected during the same period. Offshore wind is growing rapidly, with most wind turbines confined to small areas of the ocean but surpassing the number of oil structures in 2021. Our map of ocean industrialization reveals changes in some of the most extensive and economically important human activities at sea.

Disappearing cities on US coasts.

The sea level along the US coastlines is projected to rise by 0.25-0.3 m by 2050, increasing the probability of more destructive flooding and inundation in major cities1-3. However, these impacts may be exacerbated by coastal subsidence-the sinking of coastal land areas4-a factor that is often underrepresented in coastal-management policies and long-term urban planning2,5. In this study, we combine high-resolution vertical land motion (that is, raising or lowering of land) and elevation datasets with projections of sea-level rise to quantify the potential inundated areas in 32 major US coastal cities. Here we show that, even when considering the current coastal-defence structures, further land area of between 1,006 and 1,389 km2 is threatened by relative sea-level rise by 2050, posing a threat to a population of 55,000-273,000 people and 31,000-171,000 properties. Our analysis shows that not accounting for spatially variable land subsidence within the cities may lead to inaccurate projections of expected exposure. These potential consequences show the scale of the adaptation challenge, which is not appreciated in most US coastal cities.

Hybrid working from home improves retention without damaging performance.

Working from home has become standard for employees with a university degree. The most common scheme, which has been adopted by around 100 million employees in Europe and North America, is a hybrid schedule, in which individuals spend a mix of days at home and at work each week1,2. However, the effects of hybrid working on employees and firms have been debated, and some executives argue that it damages productivity, innovation and career development3-5. Here we ran a six-month randomized control trial investigating the effects of hybrid working from home on 1,612 employees in a Chinese technology company in 2021-2022. We found that hybrid working improved job satisfaction and reduced quit rates by one-third. The reduction in quit rates was significant for non-managers, female employees and those with long commutes. Null equivalence tests showed that hybrid working did not affect performance grades over the next two years of reviews. We found no evidence for a difference in promotions over the next two years overall, or for any major employee subgroup. Finally, null equivalence tests showed that hybrid working had no effect on the lines of code written by computer-engineer employees. We also found that the 395 managers in the experiment revised their surveyed views about the effect of hybrid working on productivity, from a perceived negative effect (-2.6% on average) before the experiment to a perceived positive one (+1.0%) after the experiment. These results indicate that a hybrid schedule with two days a week working from home does not damage performance.

Online images amplify gender bias.

Each year, people spend less time reading and more time viewing images1, which are proliferating online2-4. Images from platforms such as Google and Wikipedia are downloaded by millions every day2,5,6, and millions more are interacting through social media, such as Instagram and TikTok, that primarily consist of exchanging visual content. In parallel, news agencies and digital advertisers are increasingly capturing attention online through the use of images7,8, which people process more quickly, implicitly and memorably than text9-12. Here we show that the rise of images online significantly exacerbates gender bias, both in its statistical prevalence and its psychological impact. We examine the gender associations of 3,495 social categories (such as 'nurse' or 'banker') in more than one million images from Google, Wikipedia and Internet Movie Database (IMDb), and in billions of words from these platforms. We find that gender bias is consistently more prevalent in images than text for both female- and male-typed categories. We also show that the documented underrepresentation of women online13-18 is substantially worse in images than in text, public opinion and US census data. Finally, we conducted a nationally representative, preregistered experiment that shows that googling for images rather than textual descriptions of occupations amplifies gender bias in participants' beliefs. Addressing the societal effect of this large-scale shift towards visual communication will be essential for developing a fair and inclusive future for the internet.

Streamflow seasonality in a snow-dwindling world.

Climate warming induces shifts from snow to rain in cold regions1, altering snowpack dynamics with consequent impacts on streamflow that raise challenges to many aspects of ecosystem services2-4. A straightforward conceptual model states that as the fraction of precipitation falling as snow (snowfall fraction) declines, less solid water is stored over the winter and both snowmelt and streamflow shift earlier in season. Yet the responses of streamflow patterns to shifts in snowfall fraction remain uncertain5-9. Here we show that as snowfall fraction declines, the timing of the centre of streamflow mass may be advanced or delayed. Our results, based on analysis of 1950-2020 streamflow measurements across 3,049 snow-affected catchments over the Northern Hemisphere, show that mean snowfall fraction modulates the seasonal response to reductions in snowfall fraction. Specifically, temporal changes in streamflow timing with declining snowfall fraction reveal a gradient from earlier streamflow in snow-rich catchments to delayed streamflow in less snowy catchments. Furthermore, interannual variability of streamflow timing and seasonal variation increase as snowfall fraction decreases across both space and time. Our findings revise the 'less snow equals earlier streamflow' heuristic and instead point towards a complex evolution of seasonal streamflow regimes in a snow-dwindling world.

Megastudy shows that reminders boost vaccination but adding free rides does not.

Encouraging routine COVID-19 vaccinations is likely to be a crucial policy challenge for decades to come. To avert hundreds of thousands of unnecessary hospitalizations and deaths, adoption will need to be higher than it was in the autumn of 2022 or 2023, when less than one-fifth of Americans received booster vaccines1,2. One approach to encouraging vaccination is to eliminate the friction of transportation hurdles. Previous research has shown that friction can hinder follow-through3 and that individuals who live farther from COVID-19 vaccination sites are less likely to get vaccinated4. However, the value of providing free round-trip transportation to vaccination sites is unknown. Here we show that offering people free round-trip Lyft rides to pharmacies has no benefit over and above sending them behaviourally informed text messages reminding them to get vaccinated. We determined this by running a megastudy with millions of CVS Pharmacy patients in the United States testing the effects of (1) free round-trip Lyft rides to CVS Pharmacies for vaccination appointments and (2) seven different sets of behaviourally informed vaccine reminder messages. Our results suggest that offering previously vaccinated individuals free rides to vaccination sites is not a good investment in the United States, contrary to the high expectations of both expert and lay forecasters. Instead, people in the United States should be sent behaviourally informed COVID-19 vaccination reminders, which increased the 30-day COVID-19 booster uptake by 21% (1.05 percentage points) and spilled over to increase 30-day influenza vaccinations by 8% (0.34 percentage points) in our megastudy. More rigorous testing of interventions to promote vaccination is needed to ensure that evidence-based solutions are deployed widely and that ineffective but intuitively appealing tools are discontinued.

Ghost roads and the destruction of Asia-Pacific tropical forests.

Roads are expanding at the fastest pace in human history. This is the case especially in biodiversity-rich tropical nations, where roads can result in forest loss and fragmentation, wildfires, illicit land invasions and negative societal effects1-5. Many roads are being constructed illegally or informally and do not appear on any existing road map6-10; the toll of such 'ghost roads' on ecosystems is poorly understood. Here we use around 7,000 h of effort by trained volunteers to map ghost roads across the tropical Asia-Pacific region, sampling 1.42 million plots, each 1 km2 in area. Our intensive sampling revealed a total of 1.37 million km of roads in our plots-from 3.0 to 6.6 times more roads than were found in leading datasets of roads globally. Across our study area, road building almost always preceded local forest loss, and road density was by far the strongest correlate11 of deforestation out of 38 potential biophysical and socioeconomic covariates. The relationship between road density and forest loss was nonlinear, with deforestation peaking soon after roads penetrate a landscape and then declining as roads multiply and remaining accessible forests largely disappear. Notably, after controlling for lower road density inside protected areas, we found that protected areas had only modest additional effects on preventing forest loss, implying that their most vital conservation function is limiting roads and road-related environmental disruption. Collectively, our findings suggest that burgeoning, poorly studied ghost roads are among the gravest of all direct threats to tropical forests.