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Digitalised multidisciplinary conferences effectively identify and prevent imaging-related medical error in intensive care patients during the COVID-19 pandemic
Abstract This study aims to assess the effectiveness of digital multidisciplinary conferences (MDCs) in preventing imaging-related quality management (QM) events during the coronavirus-disease-19 (COVID-19) pandemic. COVID-19 challenged interdisciplinary exchange and QM measures for patient safety. Regular MDCs between radiologists and intensive care unit (ICU) physicians, introduced in our hospital in 2018, enable re-evaluation of imaging examinations and bilateral feedback. MDC protocols from 2020 to 2021 were analysed regarding imaging-related QM events. Epidemiological data on COVID-19 were matched with MDCs. 333 MDCs including 1324 radiological examinations in 857 patients (median age = 64 (IQR = 55–73) years, 66.7% male) were analysed. MDCs were held within a median of 1 day after imaging (IQR = 1–3). QM events were identified in 2.7% (n = 36/1324) of examinations. This represented a significant decrease compared to a control group from 2018/2019 (QM events identified in 14.0%, p < 0.001). QM incidence remained consistent in the pandemic cohort (regression coefficient estimate = -0.01, 95% confidence interval = [0.000, 0.000], p = 0.68). 81% (n = 29/36) of QM events were report-related, 19% process-related (n = 6/36), and 2.8% indication-related (n = 1/36). In 7.3% (n = 97/1324) of examinations, the patient was affected by COVID-19. With MDCs as an effective feedback mechanism in place, the challenges of the COVID-19 pandemic led to no increase in QM incidence. Notably, COVID status did not impact QM event occurrence.
Population encoding of observed and actual somatosensations in the human posterior parietal cortex
Cognition relies on transforming sensory inputs into a generalizable understanding of the world. Mirror neurons have been proposed to underlie this process, mapping visual representations of others’ actions and sensations onto neurons that mediate our own, providing a conduit for understanding. However, this theory has limitations. Here, we hypothesize that mirror-like responses represent one facet of a broader framework in which our brains engage internal models for cognition. We recorded populations of single neurons in the human posterior parietal cortex (PPC) of a brain–machine interface clinical trial participant implanted with a microelectrode array while she either experienced actual touch, or observed diverse tactile stimuli applied to other individuals. Two body locations were tested, on each of the participant and other individuals. Some neurons exhibited mirror-like properties, consistent with earlier literature. However, they were fragile, breaking with increased task complexity. Population responses were better characterized by generalizable and compositional basic-level features encoded within neural subspaces. These features enable the population to respond to diverse actual and observed touch stimuli and are recruited similarly for similar forms of touch. Mirror-like neurons belong within these subspaces, contributing more globally to compositionality and generalizability. We speculate that at a population-level, human PPC manifests an internal model for touch, and that cognition unfolds in the high-level human cortex by versatility in its representational building blocks. In a broad sense, we speculate that the population features we demonstrate support a broad mechanism by which the high-level human cortex enables understanding.
Comparative transcriptome analyses of different orthosiphon aristatus tissues reveal differentially expressed genes associated with flavonoid biosynthesis
Dissecting the cellular architecture and genetic circuitry of the soybean seed
Seeds are complex structures composed of three regions, embryo, endosperm, and seed coat, with each further divided into subregions that consist of tissues, cell layers, and cell types. Although the seed is well characterized anatomically, much less is known about the genetic circuitry that dictates its spatial complexity. To address this issue, we profiled mRNAs from anatomically distinct seed subregions at several developmental stages. Analyses of these profiles showed that all subregions express similar diverse gene numbers and that the small gene numbers expressed subregion specifically provide information about the biological processes that occur in these seed compartments. In parallel, we profiled RNAs in individual nuclei and identified nuclei clusters representing distinct cell identities. Integrating single-nucleus RNA and subregion mRNA transcriptomes allowed most cell identities to be assigned to specific subregions and cell types and/or cell states. The number of cell identities exceeds the number of anatomically distinguishable cell types, emphasizing the spatial complexity of seeds. We defined gene coexpression networks that underlie distinct biological processes during seed development. We showed that network distribution among subregions and cell identities is highly variable. Some networks operate in single subregions and/or cell identities, and many coexpression networks operate in multiple subregions and/or cell identities. We also showed that single subregions and cell identities possess several networks. Together, our studies provide unique insights into the biological processes and genetic circuitry that underlie the spatial landscape of the seed.
Curcumin reverses cognitive deficits through promoting neurogenesis and synapse plasticity via the upregulation of PSD95 and BDNF in mice
Climate change could amplify weak synchrony in large marine ecosystems
Climate change is increasing the frequency of large-scale, extreme environmental events and flattening environmental gradients. Whether such changes will cause spatially synchronous, large-scale population declines depends on mechanisms that limit metapopulation synchrony, thereby promoting rescue effects and stability. Using long-term data and empirical dynamic models, we quantified spatial heterogeneity in density dependence, spatial heterogeneity in environmental responses, and environmental gradients to assess their role in inhibiting synchrony across 36 marine fish and invertebrate species. Overall, spatial heterogeneity in population dynamics was as important as environmental drivers in explaining population variation. This heterogeneity leads to weak synchrony in the California Current Ecosystem, where populations exhibit diverse responses to shared, large-scale environmental change. In contrast, in the Northeast U.S. Shelf Ecosystem, gradients in average environmental conditions among locations, filtered through nonlinear environmental response curves, limit synchrony. Simulations predict that environmental gradients and response diversity will continue to inhibit synchrony even if large-scale environmental extremes become common. However, if environmental gradients weaken, synchrony and periods of large-scale population decline may rise sharply among commercially important species on the Northeast Shelf. Our approach thus allows ecologists to 1) quantify how differences among local communities underpin landscape-scale resilience and 2) identify the kinds of future climatic changes most likely to amplify synchrony and erode species stability.
Autoregulation of the glial gene reversed polarity in Drosophila
Computational-aided rational mutation design of pertuzumab to overcome active HER2 mutation S310F through antibody–drug conjugates
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA. This variant, with only two mutations (T30S/D31A) located on its heavy chain, effectively reinstates binding to the mutated antigen, at the expense of a 35-fold reduction in binding affinity to HER2 (S310F) compared to the wild-type pair. Subsequently, Ptz-SA demonstrates potent killing capacity through antigen-dependent cytotoxicity. Moreover, upon engineering Ptz-SA into antibody–drug conjugates, such as Ptz-SA-MMAE, it manifests notable in vitro and in vivo antitumor efficacy by efficiently delivering cytotoxic payload into tumor cells expressing HER2 (S310F). Cryoelectron microscopy studies elucidate the molecular mechanism underlying the restored binding ability of Ptz-SA toward the S310F mutation. The steric hindrance induced by the S310F mutation is efficiently circumvented by the T30S and D31A mutations, which provides adequate space to accommodate the larger phenylalanine. Additionally, Ptz-SA also exhibits binding capacity to HER2 (S310Y), another mutation occurring at the S310 site of HER2 with high frequency. The computational-aided evolution of pertuzumab provides an alternative strategy for overcoming point mutation-mediated resistance to therapeutic antibodies.
Healthcare professionals and the public sentiment analysis of ChatGPT in clinical practice
<i>Salmonella</i> infection accelerates postnatal maturation of the intestinal epithelium
Postnatal establishment of enteric metabolic, host–microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Salmonella Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators. Cytokine stimulation of neonatal intestinal epithelial stem cell organoids suggests a network of synergistic and antagonistic cytokine effects with a significant contribution of IL-22, IL-4/IL-13, TNF, and IL-6 to infection-induced enterocyte reprogramming. Our findings demonstrate that the infection-associated immune cell activation disrupts physiological postnatal tissue maturation and may thereby worsen clinical outcomes and alter the neonatal-adult transition.
Systemic lupus erythematosus is associated with an increased risk of cervical artery dissection
AbstractLimited evidence suggests that autoimmune diseases are associated with an increased risk of cervical artery dissection (CeAD). We hypothesized individuals with systemic lupus erythematosus (SLE) would have an increased risk of CeAD following SLE diagnosis compared to matched non-lupus controls. We queried a de-identified United States electronic medical records network (TriNetX, Inc.) for individuals aged 10 and older from 2012 to 2020, for two cohorts: (1) SLE and (2) non-lupus controls, excluding those with prior CeAD. We used propensity matching to control for confounding variables and calculated the risk ratio (RR) for CeAD occurring over four years’ follow-up, secondarily exploring cumulative incidence. After matching, both cohorts contained 77,008 patients, who were mostly female (89%). The incidence and risk of CeAD was significantly greater among those with SLE compared to matched non-lupus controls [95% CI] (0.08% vs. 0.04%; RR = 2.33 [1.49;3.66]; P < 0.0001). These findings support the hypothesis that SLE is a risk factor for CeAD. Additional research is needed to identify the mechanisms that may underly the SLE-CeAD association and examine the potential association between other autoimmune diseases and CeAD.
A lever hypothesis for Synaptotagmin-1 action in neurotransmitter release
Neurotransmitter release is triggered in microseconds by Ca 2+ -binding to the Synaptotagmin-1 C 2 -domains and by SNARE complexes that form four-helix bundles between synaptic vesicles and plasma membranes, but the coupling mechanism between Ca 2+ -sensing and membrane fusion is unknown. Release requires extension of SNARE helices into juxtamembrane linkers that precede transmembrane regions (linker zippering) and binding of the Synaptotagmin-1 C 2 B domain to SNARE complexes through a “primary interface” comprising two regions (I and II). The Synaptotagmin-1 Ca 2+ -binding loops were believed to accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers, or helping bridge the membranes, but SNARE complex binding through the primary interface orients the Ca 2+ -binding loops away from the fusion site, hindering these putative activities. To clarify this paradox, we have used NMR and fluorescence spectroscopy. NMR experiments reveal that binding of C 2 B domain arginines to SNARE acidic residues at region II remains after disruption of region I, and that a mutation that impairs spontaneous and Ca 2+ -triggered neurotransmitter release enhances binding through region I. Moreover, fluorescence assays show that Ca 2+ does not induce dissociation of Synaptotagmin-1 from membrane-anchored SNARE complex but causes reorientation of the C 2 B domain. Based on these results and electrophysiological data described by Toulme et al. ( https://doi.org/10.1073/pnas.2409636121 ), we propose that upon Ca 2+ binding the Synaptotagmin-1 C 2 B domain reorients on the membrane and dissociates from the SNAREs at region I but not region II, acting remotely as a lever that pulls the SNARE complex and facilitates linker zippering or other SNARE structural changes required for fast membrane fusion.
Real-time monitoring and prediction of remote operator fatigue in plateau deep mining based on dynamic Bayesian networks
Oncogenic IDH1 <sup>mut</sup> drives robust loss of histone acetylation and increases chromatin heterogeneity
Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2 mut ) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype. Yet, the complete depiction of the epigenetic alterations in IDH mut cells has not been thoroughly explored. Here, we applied an unbiased approach, leveraging epigenetic-focused cytometry by time-of-flight (CyTOF) analysis, to systematically profile the effect of mutant-IDH1 expression on a broad panel of histone modifications at single-cell resolution. This analysis revealed extensive remodeling of chromatin patterns by mutant-IDH1, with the most prominent being deregulation of histone acetylation marks. The loss of histone acetylation occurs rapidly following mutant-IDH1 induction and affects acetylation patterns over enhancers and intergenic regions. Notably, the changes in acetylation are not predominantly driven by 2-HG, can be rescued by pharmacological inhibition of mutant-IDH1, and reversed by acetate supplementations. Furthermore, cells expressing mutant-IDH1 show higher epigenetic and transcriptional heterogeneity and upregulation of oncogenes such as KRAS and MYC, highlighting its tumorigenic potential. Our study underscores the tight interaction between chromatin and metabolism dysregulation in glioma and highlights epigenetic and oncogenic pathways affected by mutant-IDH1-driven metabolic rewiring.
Association between abdominal obesity and nutritional supplement use among Iranian adults in the Shahedieh cohort study
AbstractThe relationship between the use of supplements and the presence of abdominal obesity is a topic that is currently being debated. The purpose of the present study was to evaluate the existence of such an association. The current cross-sectional investigation included a population of 9878 individuals who were the focus of the study’s initial phase in the Shahedieh cohort study, conducted in Yazd, Iran. Waist circumference was measured with the help of an inflexible tape measure. In addition, the data regarding the consumption of various supplements, including multivitamins, folic acid, ferric compounds, omega 3, calcium, vitamin D, zinc, and other supplements, were collected through interviews conducted by trained interviewers. Among the entire sample, 4785 individuals (50.6%) were found to have abdominal obesity, while 4093 individuals (43.3%) reported using at least one type of supplements. In the simple regression analysis, all of the supplements, except for multivitamins and zinc, were identified as adverse factors for abdominal obesity. However, in the multivariable regression analysis, only ferric compounds remained significant as a protective factor (OR = 0.73, 95%CI: 0.57‒0.94). The findings of this study suggest that dietary supplements, particularly ferric compounds, may have implications for managing abdominal obesity. These findings could inform public health strategies by incorporating ferric compound supplementation into dietary interventions aimed at reducing abdominal obesity prevalence. Furthermore, the potential clinical application of ferric compounds highlights the need for integrating nutritional approaches in obesity management programs. However, longitudinal studies are needed to establish causal relationships and confirm the long-term effectiveness and safety of such interventions.
US Corn Belt enhances regional precipitation recycling
Precipitation recycling, where evapotranspiration (ET) from the land surface contributes to precipitation within the same region, is a critical component of the water cycle. This process is especially important for the US Corn Belt, where extensive cropland expansions and irrigation activities have significantly transformed the landscape and affected the regional climate. Previous studies investigating precipitation recycling typically relied on analytical models with simplifying assumptions, overlooking the complex interactions between groundwater hydrology and agricultural management. In this study, we use high-resolution climate models coupled with an explicit water vapor tracer algorithm to quantify the impacts of shallow groundwater, dynamic crop growth, and irrigation on regional precipitation recycling in the US Corn Belt. We find that these coupled groundwater–crop–irrigation processes reduce surface temperatures and increase the growing season precipitation. The increase in precipitation is attributed to a significant enhancement of the precipitation recycling ratio from 14 to 18%. This enhanced precipitation recycling is stronger in a dry year than normal and wet years, depending on both large-scale moisture transport and local ET. Our study underscores the critical role of groundwater hydrology and agricultural management in altering the regional water cycle, with important implications for regional climate predictions and food and water security.
A case study on using a large language model to analyze continuous glucose monitoring data
Abstract Continuous glucose monitors (CGM) provide valuable insights about glycemic control that aid in diabetes management. However, interpreting metrics and charts and synthesizing them into linguistic summaries is often non-trivial for patients and providers. The advent of large language models (LLMs) has enabled real-time text generation and summarization of medical data. The objective of this study was to assess the strengths and limitations of using an LLM to analyze raw CGM data and produce summaries of 14 days of data for patients with type 1 diabetes. We first evaluated the ability of GPT-4 to compute quantitative metrics specific to diabetes found in an Ambulatory Glucose Profile (AGP). Then, using two independent clinician graders, we evaluated the accuracy, completeness, safety, and suitability of qualitative descriptions produced by GPT-4 across five different CGM analysis tasks. GPT-4 performed 9 out of the 10 quantitative metrics tasks with perfect accuracy across all 10 cases. The clinician-evaluated CGM analysis tasks had good performance across measures of accuracy [lowest task mean score 8/10, highest task mean score 10/10], completeness [lowest task mean score 7.5/10, highest task mean score 10/10], and safety [lowest task mean score 9.5/10, highest task mean score 10/10]. Our work serves as a preliminary study on how generative language models can be integrated into diabetes care through data summarization and, more broadly, the potential to leverage LLMs for streamlined medical time series analysis.
Deciphering the artificial evolution of domesticated plants within dynamic habitats
Vertical wind profile distribution within canopy layer based on representative geometry model using wind tunnel experiment
AbstractThis study examined the mean and turbulent wind speed distribution within the canopy height of a tropical urban campus based on a representative geometry model via wind tunnel experiments. The vertical wind profiles were analysed around two high-rise buildings, Menara Razak (MR) and Residensi Tower (RT) at both wind directions (22.5° and 202.5°). To examine the influence of high-rise buildings on strong wind, the collected data of mean wind speed (u), root mean square (urms), and skewness (SK) were analysed. Effects of the wind direction, building layout or arrangement and building geometry under the canopy height were also examined. The results show that the building layout influenced the wind distribution within the target site, and the approaching wind flow direction also influenced the wind flow interaction with the building. The height of the target building (H) influenced the distance traveled by the vortices in the wake flow. For the MR and RT cases, the vortices could be affected up to a minimum distance of H and 1.5H, respectively. The study demonstrates that the building layout significantly influences the distribution of wind speeds within the canopy height of a tropical urban campus.