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Transforming literature screening: The emerging role of large language models in systematic reviews
Systematic reviews (SR) synthesize evidence-based medical literature, but they involve labor-intensive manual article screening. Large language models (LLMs) can select relevant literature, but their quality and efficacy are still being determined compared to humans. We evaluated the overlap between title- and abstract-based selected articles of 18 different LLMs and human-selected articles for three SR. In the three SRs, 185/4,662, 122/1,741, and 45/66 articles have been selected and considered for full-text screening by two independent reviewers. Due to technical variations and the inability of the LLMs to classify all records, the LLM’s considered sample sizes were smaller. However, on average, the 18 LLMs classified 4,294 (min 4,130; max 4,329), 1,539 (min 1,449; max 1,574), and 27 (min 22; max 37) of the titles and abstracts correctly as either included or excluded for the three SRs, respectively. Additional analysis revealed that the definitions of the inclusion criteria and conceptual designs significantly influenced the LLM performances. In conclusion, LLMs can reduce one reviewer´s workload between 33% and 93% during title and abstract screening. However, the exact formulation of the inclusion and exclusion criteria should be refined beforehand for ideal support of the LLMs.
Enabling next-generation engineered TCR-T therapies based on high-throughput TCR discovery from diagnostic tumor biopsies
Network pharmacology combined with experimental verification for exploring the potential mechanism of phellodendrine against depression
Pore pressure inhibits clustering of induced earthquakes in Western Canada
Induced earthquakes are manifestations of highly heterogeneous distributions of effective stress changes imparted by anthropogenic activities such as hydraulic fracturing and wastewater injection. It is critical to disentangle the mechanisms behind these earthquakes to better assess seismic risk. Here, a clustering methodology is applied to a catalog of 21,536 induced earthquakes detected during a 36-d hydraulic stimulation program in Western Canada. The results reveal that clustered events nucleate at short recurrence times generally less than 6 min. Notably, the clustered events are not characterized by short interevent distances as seen in regional-scale studies. Numerical modeling reveals that earthquakes cluster preferentially in regions of significantly lower pore pressure change ( Δ P ). Furthermore, clustered earthquakes exhibit significantly more chain-like topologies with decreasing Δ P , in agreement with laboratory studies showing that fault materials transition to rate-strengthening behavior with increasing Δ P . Proxy estimates for pore pressure change suggest these observations are consistent across Western Canada, and highlight the potential for significant temporal segmentation of induced earthquake processes.
Modeling bacterial interactions uncovers the importance of outliers in the coastal lignin-degrading consortium
Compartmental Models Driven by Renewal Processes: Survival Analysis and Applications to SVIS Epidemic Models
The small GTPase MRAS is a broken switch
Fuzzy logic applied to tunning mutation size in evolutionary algorithms
Completion of lunar magma ocean solidification at 4.43 Ga
Crystallization of the lunar magma ocean yielded a chemically unique liquid residuum named KREEP. This component is expressed as a large patch on the near side of the Moon and a possible smaller patch in the northwest portion of the Moon’s South Pole-Aitken basin on the far side. Thermal models estimate that the crystallization of the lunar magma ocean (LMO) could have spanned from 10 and 200 My, while studies of radioactive decay systems have yielded inconsistent ages for the completion of LMO crystallization covering over 160 My. Here, we show that the Moon achieved >99% crystallization at 4,429 ± 76 Ma, indicating a lunar formation age of ~4,450 Ma or possibly older. Using the 176 Lu– 176 Hf decay system ( t 1/2 = 37 Gy), we found that the initial 176 Hf/ 177 Hf ratios of lunar zircons with varied U–Pb ages are consistent with their crystallization from a KREEP-rich reservoir with a consistently low 176 Lu/ 177 Hf ratio of 0.0167 that emerged ~140 My after solar system formation. The previously proposed younger model age of ~4.33 Ga for the source of mare basalts (240 My after solar system formation) might reflect the timing of a large impact. Our results demonstrate that lunar magma ocean crystallization took place while the Moon was still battered by planetary embryos and planetesimals leftover from the main stage of planetary accretion. The study of Lu–Hf model ages for samples brought back from the South Pole-Aitken basin will help to assess the lateral continuity of KREEP and further understand its significance in the early history of the Moon.
Massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS)
An analytical study for predicting incipient motion velocity of sediments under ice cover
Le Chatelier’s concrete conundrum
Mutations to transcription factor MAX allosterically increase DNA selectivity by altering folding and binding pathways
Exploring the impact of entrepreneurial orientation and market orientation on entrepreneurial performance in the context of environmental uncertainty
Fundamental constraints and questions from the study of Martian meteorites and the need for returned samples
Physical materials from planetary bodies are crucial for understanding fundamental processes that constrain the evolution of the solar system, as samples can be analyzed at high precision and accuracy in Earth-based laboratories. Mars is the only planet outside of Earth from which we possess samples in the form of meteorites. Martian meteorites (n > 350) have enabled constraints to be placed on various aspects of the red planet’s formation and evolution, notably: that Mars accreted and differentiated rapidly; that the planet has a complex volatile element evolution; and that it has always been volcanically active with a rich and diverse magmatic history. Meteorites have limitations, however, with lack of field context, restricted lithological diversity compared to the martian surface, and with no sampling of a major portion of Mars’ history between 4.1 and 2.4 billion years ago. Returned samples from Mars have the potential to fill these gaps and answer many open questions driven by the study of meteorites, as well as reveal new fundamental research questions. Key questions that Mars Sample Return is likely to answer regard the basic evolution of the martian interior and surface, its potential for habitability and the possibility of past life, and calibration of age dating of the martian surface. Samples of various lithologies and different ages collected at Jezero crater by the Perseverance rover will aid in better understanding our own planet and will answer outstanding questions regarding Mars’ future geological evolution and habitability.
Inhalable biohybrid microrobots: a non-invasive approach for lung treatment
Abstract Amidst the rising prevalence of respiratory diseases, the importance of effective lung treatment modalities is more critical than ever. However, current drug delivery systems face significant limitations that impede their efficacy and therapeutic outcome. Biohybrid microrobots have shown considerable promise for active in vivo drug delivery, especially for pulmonary applications via intratracheal routes. However, the invasive nature of intratracheal administration poses barriers to its clinical translation. Herein, we report on an efficient non-invasive inhalation-based method of delivering microrobots to the lungs. A nebulizer is employed to encapsulate picoeukaryote algae microrobots within small aerosol particles, enabling them to reach the lower respiratory tract. Post nebulization, the microrobots retain their motility (~55 μm s-1) to help achieve a homogeneous lung distribution and long-term retention exceeding five days in the lungs. Therapeutic efficacy is demonstrated in a mouse model of acute methicillin-resistant Staphylococcus aureus pneumonia using this pulmonary inhalation approach to deliver microrobots functionalized with platelet membrane-coated polymeric nanoparticles loaded with vancomycin. These promising findings underscore the benefits of inhalable biohybrid microrobots in a setting that does not require anesthesia, highlighting the substantial translational potential of this delivery system for routine clinical applications.
Proteomic, metabolomic and lipidomic profiles in community acquired pneumonia for differentiating viral and bacterial infections
Abstract Community-acquired pneumonia (CAP) has a significant impact on public health, especially in light of the recent SARS-CoV-2 pandemic. To enhance disease characterization and improve understanding of the underlying mechanisms, a comprehensive analysis of the plasma lipidome, metabolome and proteome was conducted in patients with viral and bacterial CAP infections, including those induced by SARS-CoV-2. Lipidomic, metabolomic and proteomic profiling were conducted on plasma samples of 69 patients suffering either from viral or bacterial CAP. Lipid and metabolite analyses were LC-MS-based, while proteomic analyses were performed using multiple panels of the Olink platform. Statistical methods, machine learning and pathway analyses were conducted investigating differences between the infection types. Through comparison of the bacterial and viral pathogen groups, distinct signatures were observed in the plasma profiles. Notably, linoleic acid-derived inflammation signaling metabolites (EpOME and DiHOME) were increased in viral CAP compared to bacterial CAP. Similarly, proteins involved in cellular immune response and apoptosis (LAG-3 and TRAIL) showed elevated levels in viral CAP, while bacterial CAP exhibited notable elevation in pattern-recognizing receptors (CLEC4D and EN-RAGE). Additionally, within the lipidomic profile at baseline, several lipids displayed notable differences between viral and bacterial pneumonia, including bile acids (GCA, TCA, TCDCA), various tri- and diglycerides (TGs and DGs), and several phosphatidylcholines (PCs). These findings hold promise for facilitating the differential diagnosis of viral and bacterial pulmonary infections based on the systemic lipidome, metabolome and proteome, enabling timely treatment decisions. Additionally, they highlight potential targets for drug research, advancing therapeutic interventions in CAP. By providing valuable insights into the molecular characterization of CAP, this study contributes to the improvement of understanding the disease and, ultimately, the development of effective treatment strategies.
Perspectives on Mars Sample Return: A critical resource for planetary science and exploration
Mars Sample Return (MSR) has been the highest flagship mission priority in the last two Planetary Decadal Surveys of the National Academies of Science, Engineering, and Medicine (hereafter, “the National Academies”) and was the highest priority flagship for Mars in the Decadal Survey that preceded them. This inspirational and challenging campaign, like the Apollo program’s returned lunar samples, will potentially revolutionize our understanding of Mars and help inform how other planets are explored. MSR’s technological advances will keep the NASA and European Space Agency at the forefront of planetary exploration, and data on returned samples will fill knowledge gaps for future human exploration. Investigations of the ancient rocks collected in and around Jezero crater, as well as samples of the regolith and atmosphere, will be fundamentally different in scope, depth, and certainty from what is achievable with spaceborne observations. Returned Mars samples can address critical science issues including the discovery and characterization of ancient extraterrestrial life, prebiotic organic chemistry, the history of habitable planetary environments, planetary geological, geochemical, and geophysical evolution, orbital dynamics of bodies in the early Solar System, and the formation and evolution of atmospheres.
Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling
Abstract Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. We report analyses of rare variants that impact birth weight when carried by either fetus or mother, using whole exome sequencing data in up to 234,675 participants. Rare protein-truncating and deleterious missense variants are collapsed to perform gene burden tests. We identify 9 genes; 5 with fetal-only effects on birth weight, 1 with maternal-only effects, 3 with both, and observe directionally concordant associations in an independent sample. Four of the genes were previously implicated by GWAS of birth weight. IGF1R and PAPPA2 (fetal and maternal-acting) have known roles in insulin-like growth factor bioavailability and signalling. PPARG, INHBE and ACVR1C (fetal-acting) are involved in adipose tissue regulation, and the latter two also show associations with favourable adiposity patterns in adults. We highlight the dual role of PPARG (fetal-acting) in adipocyte differentiation and placental angiogenesis. NOS3 (fetal and maternal-acting) , NRK (fetal), and ADAMTS8 (maternal-acting) have been implicated in placental function and hypertension. To conclude, our analysis of rare coding variants identifies regulators of fetal adipose tissue and fetoplacental angiogenesis as determinants of birth weight, and further evidence for the role of insulin-like growth factors.