Browse Articles

Metabolic risk and metabolic dysfunction–associated steatotic liver disease and steatohepatitis in cognitive decline: A retrospective cohort study

Objective To determine whether metabolic risk factors (MRFs), metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic dysfunction–associated steatohepatitis (MASH) are associated with incident mild cognitive impairment (MCI), vascular dementia (VD), and Alzheimer disease (AD). Design Retrospective cohort study using TriNetX (2003–2023) with Propensity score matching. Setting Multicenter, population-based sample from 69 U.S. healthcare organizations in the TriNetX electronic health record. Participants Adults aged ≥50 years with ≥1 outpatient visit and sufficient clinical/laboratory data. Individuals with prior diagnoses of cognitive impairment, cerebrovascular disease, advanced liver disease, malignancy, schizophrenia, or substance use disorders were excluded. Two matched cohorts were constructed: one with 3,546,833 individuals with MRFs and 3,546,833 healthy controls, and another with 525,844 individuals with MASLD/MASH and 525,844 with MRFs only. Matching was based on age, sex, race, and ethnicity. Primary and secondary outcome measures Incident MCI, VD, and AD, identified using ICD-10 codes, assessed at 5–20-year intervals. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. Outcomes were prespecified. Results Among 7,818,146 participants (mean [SD] age, 64.9 [8.8] years; 52.0% female), individuals with MRFs had higher odds of VD (OR, 1.65; 95% CI, 1.63–1.67), MCI (OR, 1.45; 95% CI, 1.42–1.48), and AD (OR, 1.21; 95% CI, 1.19–1.24) vs healthy controls. Compared to the MRF group, individuals with MASLD/MASH had lower odds of VD (OR, 0.86; 95% CI, 0.83–0.89) and AD (OR, 0.83; 95% CI, 0.78–0.88), but higher odds of MCI (OR, 1.37; 95% CI, 1.30–1.44); all p  < .001. Conclusions In this large, propensity-matched retrospective cohort study, MRFs were independently associated with significantly increased long-term odds of MCI, VD, and AD. MASLD/MASH demonstrated a divergent cognitive risk profile relative to MRFs alone—characterized by higher odds of MCI but paradoxically lower odds of VD and AD, a pattern that warrants cautious interpretation given potential competing mortality risk, survivor bias, and residual confounding. These findings suggest that MASLD/MASH is associated with a distinct cognitive trajectory, highlighting the importance of early cognitive surveillance in this population.

Association between fluid administration and 28-day mortality in sepsis: a retrospective cohort study

Neutrino’s nursery found: the ‘Shadow Blaster’

Phylo-Plex: a phylogenetically informed, low-cost amplicon sequencing platform for deployable high-resolution genomic epidemiology

Abstract Genomic pathogen surveillance is a powerful tool for public health and research, but is costly and unachievable in low-resource settings. Most sub-genomic typing methods sacrifice resolution whilst remaining costly. We developed “Phylo-Plex”, a novel approach that identifies information-rich genomic regions to maximise phylogenetic information whilst minimising the number of regions. Applied to Treponema pallidum and Neisseria gonorrhoeae , we designed a high-resolution multiplex PCR sequencing scheme for lineage tracking pathogens with different extremes of genome variation. For Treponema pallidum , we also designed and evaluated the Phylo-Plex scheme in the laboratory and field settings by sequencing 72 clinical samples using MinION Flongle cells. Our T. pallidum scheme comprising 59 multiplex amplicons achieved high discrimination of fine-scale sublineages comparable to those defined using whole genomes, and demonstrating a qPCR detection limit ≤Ct 32. Variant calls from MinION amplicon sequencing were highly correlated with Illumina whole genome sequencing. We successfully deployed the method in a low-resource laboratory in Zimbabwe, costed at <£300/24 samples (£12.47/sample). Phylo-Plex enables low-cost tracking of priority pathogenic lineages in low resource settings and at scale.

Complex patterns of functional change among TBI survivors from discharge to 6-month follow-up: Findings from a registry-based cohort study

Background Functional recovery after traumatic brain injury (TBI) is heterogeneous, and reliance on single time-point outcomes may obscure meaningful post-discharge change. Objective To identify early clinical, laboratory, and radiologic factors associated with functional change between hospital discharge and six-month follow-up using the Glasgow Outcome Scale-Extended (GOSE). Methods In this longitudinal study, 2,948 TBI survivors aged 12 years or older admitted to a tertiary trauma center underwent GOSE assessment at discharge and six months post-discharge. Functional trajectories were classified as recovering, stable, or regressing. Multinomial logistic regression evaluated associations between early variables and functional trajectories. Analyses were additionally stratified by discharge GOSE to assess statistical effects. Results Substantial bidirectional functional change occurred after discharge. Several variables, including age, Glasgow Coma Scale, subarachnoid or intraventricular hemorrhage, hemoglobin, and coagulation indices, were associated with both recovery and regression. Discharge GOSE strongly predicted subsequent change but increased the odds of both improvement and decline. Subgroup analyses indicated many unexpected associations reflected ceiling and floor effects and regression to the mean. Nevertheless, some predictors showed consistent directional effects: in non-severe TBI, age 40–74 years, low admission blood glucose, and higher platelet counts; and in severe TBI, age > 40 years, low admission blood glucose, pneumocephalus, and bilateral fixed pupils. Conclusions Post-TBI functional outcomes follow complex, often unpredictable trajectories. These findings highlight limitations of static early prognostication and support a trajectory-oriented approach to post-discharge TBI care.

Deformation failure mechanism of deep high-stress fractured soft rock roadways and active-passive full-space collaborative control technology

Author Correction: The balance between stability and plasticity of the visual word form area in dyslexia

Compressive stress inhibits proliferation in AsPC-1 pancreatic cancer cells and reduction of Myc protein

Cancer cells grow in confined tumor microenvironments and push the surrounding tissue, which reacts and exposes them to compressive stress. Previous studies have revealed that compressive stress inhibits proliferation in breast and colorectal cancer cells. It has been reported that pancreatic tumors accumulate compressive stress in vivo , but it is not well understood whether compressive stress regulates proliferation in pancreatic cancer cells. Therefore, the effect of compressive stress on the proliferation of human pancreatic cancer cells was investigated in this study. We found that the growth of compressed AsPC-1 human pancreatic cancer cells was slower than that of uncompressed cells. Furthermore, the protein expression of Myc was reduced in compressed cells, which inhibited their proliferation. In addition, the expression of Snail, which is correlated with poor prognosis in pancreatic cancer patients, was promoted by compressive stress and the inhibition of Myc. These results suggest that compressive stress inhibits proliferation and triggers Snail expression via the reduction of Myc protein in AsPC-1 pancreatic cancer cells.

The effectiveness of pulpotomy in mature permanent posterior teeth with irreversible pulpitis: a systematic review and meta-analysis

Incoming US science academy chief vows to ‘double down’ on research

The distribution of Earth’s wind-blown sand dunes

A qualitative analysis of Chinese novice general dentists’ perspectives on using ergonomic loupes in clinical practice

Background Ergonomic loupes are the next-generation loupes with built-in refractive prisms that enable the user to sit up straight, look straight ahead, and reduce neck tilt while viewing the operating field from down below. They differ greatly from traditional loupes in optic design and viewer perspective. They appeared on the market in 2022 and are quickly gaining popularity in China. In this study, we sought to use semi-structured interviews and thematic analysis to assess the perspectives of novice Chinese general dentists on using ergonomic loupes in clinical practice. Methods The study population consisted of nineteen general dentistry residents undergoing training at Peking University Third Hospital in Beijing, China. Semi-structured interviews were conducted individually with participants. The interview data were analyzed thematically using NVivo 11 software. Results The findings revealed that the benefits of using ergonomic loupes included enhanced visual acuity, more precision, improved posture, and improved treatment quality. Main disadvantages included discomfort from use, splash protection issue, fixed viewpoint, and limited field of view. There was typically a brief adaptation process for the new user. Participants were weighing cost and benefit in deciding whether and where to use ergonomic loupes. Comparative experience showed that ergonomic loupes had ergonomic advantages, while traditional loupes had hand-eye coordination advantages. Conclusion The participants had overall positive perspectives on using ergonomic loupes in clinical practice. Comparative experience showed that ergonomic loupes had ergonomic advantages, while traditional loupes had hand-eye coordination advantages.

Molecular design beyond training data with novel extended objective functionals of generative AI models driven by quantum annealing computer

Abstract Deep generative modeling to stochastically design small molecules is an emerging technology for accelerating drug discovery and development. However, one major issue in molecular generative models is their lower frequency of drug-like compounds. To solve this problem, we develop a novel, quantum annealing, generative-model approach for optimizing deep generative models, an approach that includes integrating with a D-Wave annealing quantum computer. Of particular note, our neural hash function (NHF) is used simultaneously as a regularization scheme and binarization scheme, of which the latter is for transformation between continuous and discrete signals of the classical and quantum neural networks, respectively, in the error evaluation (i.e., objective) function. The compounds generated via the quantum-annealing generative models exhibit higher quality in both validity and drug-likeness than those generated via the fully-classical models, and even exceed the training data in terms of drug-likeness features, without any restraints and conditions to deliberately induce such an optimization. These results suggest that quantum annealing could be used as a stochastic generator integrated with our novel neural network architectures for extending the performance of feature space sampling and the extraction of characteristic features in drug design.

Direct correspondence between liquid and glass polymorphism in densely packed metallic alloys

Complete genomes of two Ikeda-genotype Orientia tsutsugamushi isolates from South Korea reveal within-lineage divergence and contrast with the Boryong reference strain

Orientia tsutsugamushi strain Ikeda is a scrub typhus reference strain originally described in Japan, and Ikeda 56-kDa type-specific antigen sequence types have also been reported in South Korea. However, complete genome resources for South Korean Ikeda-genotype isolates remain limited. Here, we generated complete genomes for two archived clinical O. tsutsugamushi isolates from northern South Korea, CH219 and K4-135, using a PacBio HiFi and Illumina hybrid assembly approach and compared them with the Japanese reference strain Ikeda and the South Korean reference strain Boryong. Both genomes were assembled as single circular chromosomes and contained a substantial fraction of duplicated identical coding sequences, consistent with the highly repetitive nature of O. tsutsugamushi genomes. Strains CH219 and K4-135 had identical 56-kDa TSA sequences and MLST profiles to those of the Ikeda reference strain and clustered within the Ikeda-associated clade in recombination-filtered core-genome phylogeny and ANI analyses. Within this comparison, the two South Korean isolates showed more closely related to each other than to the Japanese Ikeda reference genome. Whole-genome dot plots further indicated structural variation among the Ikeda-associated genomes. Insertion sequence (IS) profiling showed differences in IS-related CDS copy number patterns between the Boryong reference genome and the Ikeda-associated genomes, with strain Boryong showing a higher observed number of ISOt6-related CDS hits and fewer high-identity ISOt3-related hits under the applied thresholds. Together, these genomes provide new resources for Ikeda-like O. tsutsugamushi strains detected in South Korea and support the need for expanded complete and well-supported whole-genome data to better understand genome diversity in scrub typhus agents.

Integrated eco-hydrological and vegetation productivity analysis of wetland landscapes in Madhubani, Bihar (2002–2024)

Abstract Wetlands are highly productive ecosystems that regulate hydrological processes, store carbon, and support rich biodiversity, yet they remain highly vulnerable to hydro-climatic variability and anthropogenic pressures. This study examines long-term eco-hydrological dynamics influencing wetland systems in the Madhubani district of North Bihar during 2002–2024 using an integrated framework of climatic, hydrological, and ecological indicators. Rainfall trends were analyzed alongside Actual and Potential Evapotranspiration (ET, PET), Standardised Water Deficit (SWD), Wetness Index (WI), Gross and Net Primary Productivity (GPP, NPP), and remote sensing indices, including the Modified Normalized Difference Water Index (MNDWI) and Soil-Adjusted Vegetation Index (SAVI) derived from Terra MODIS and Landsat datasets. Trend analysis indicates a non-significant but persistent decline in annual rainfall (Z = − 1.33; Sen’s slope = − 7.53 mm year −1 ), with stronger decreases during the monsoon season (− 8.65 mm year −1 ). ET (320–720 mm yr −1 ) remained substantially lower than PET (2030–2520 mm yr −1 ), indicating persistent atmospheric water demand and increasing moisture stress, as reflected in Standardised Water Deficit variability and relatively low Wetness Index values. Vegetation productivity exhibited considerable interannual variability, with GPP ranging from ~ 770 to 1530 g C m −2  yr −1 and NPP from ~ 100 to 430 g C m −2  yr −1 . Both productivity metrics declined sharply during 2012–2015, suggesting sensitivity to monsoon rainfall variability. Spatial analysis reveals significant hydrological and ecological changes. Post-monsoon moderately wet areas declined from 75.10% (2002) to 55.27% (2024), while dry zones expanded from 17.24 to 39.55%, indicating progressive wetland contraction. Vegetation dynamics derived from SAVI show spatial redistribution of vegetation cover, with dense vegetation increasing from 21.32 to 26.18%, particularly in northern areas associated with irrigation supported agriculture. Correlation analysis further demonstrates strong eco-hydrological coupling, with rainfall positively correlated with the wetness index and negatively associated with water deficit. Overall, the findings indicate a shifting eco-hydrological regime in Madhubani characterized by declining rainfall reliability, increasing moisture stress, wetland shrinkage, and changing vegetation patterns. These trends highlight the need for integrated wetland management and climate-resilient water resource strategies to sustain ecological stability in the floodplain landscapes of North Bihar.

Author Correction: The mitochondrial β-oxidation enzyme HADHA restrains hepatic glucagon response by promoting β-hydroxybutyrate production

In silico antimicrobial resistance profiling of 1,240 Stenotrophomonas maltophilia genomes: AMR gene prevalence, temporal evolution, and ST-specific associations

Stenotrophomonas maltophilia is an opportunistic pathogen with clinically important multidrug resistance, yet large-scale genome-based analyses integrating population structure, resistance determinants, and epidemiological metadata remain limited. We analyzed 2,419 publicly available genomes retrieved from NCBI GenBank. After quality control with CheckM, 2,389 assemblies passed filtering criteria, and species identity was further evaluated by average nucleotide identity using FastANI. A final curated dataset of 1,240 confirmed S. maltophilia genomes was retained for downstream analyses. Antimicrobial resistance determinants were identified using AMRFinderPlus, sequence types were assigned by multilocus sequence typing, and temporal, geographic, host-associated, and gene co-occurrence analyses were performed. The 1,240 genomes represented isolates collected between 1900 and 2025 from 40 countries. Geographic metadata were available for 1,239 isolates, host source for 1,239 isolates, and collection year for 1,105 isolates. Human-derived isolates predominated, whereas animal-derived isolates were rare and environmental isolates were absent. MLST assigned 876 isolates to 97 sequence types, with ST5, ST4, ST1, ST31, and ST162 as the most prevalent lineages. The resistome comprised 69 unique resistance-associated genes across 12 functional classes and showed a bimodal structure, with a highly conserved intrinsic core and a sparse accessory component. Core genes included emrA , emrB , emrC , smeF , blaL1 , aac (6′)- Iz , aph (6), aph (3′)- IIc , ermB , and ermC , most of which occurred at very high prevalence. In contrast, acquired determinants such as sul2 , tet (G), aadA2 , blaNDM-1 , blaGES-1 , and blaOXA-74 were infrequent. Plasmid replicons were also uncommon, supporting a predominantly chromosomal resistance architecture. Temporal analyses showed that intrinsic genes were present in the earliest available isolates, whereas acquired genes appeared only in recent decades and generally remained rare. Several acquired genes, including floR , aph (3′′)- Ib , aph (6)- Id , and aac (6′)- Ib4 , declined over time, while no acquired resistance determinant showed a significant increasing trend. Gene presence pattern and co-occurrence analyses identified dominant conserved resistome configurations and a smaller set of variable accessory modules associated with putative mobile genetic elements. Comparative analysis further showed enrichment of intrinsic efflux-associated determinants in clinical isolates, whereas non-clinical isolates carried a broader diversity of acquired aminoglycoside resistance genes. These findings indicate that the global resistome of S. maltophilia is dominated by conserved intrinsic, chromosomally encoded resistance determinants, whereas acquired resistance genes remain rare, sporadic, and lineage-associated. This curated genome-scale framework provides a resource for surveillance and for future studies linking resistome evolution, mobile genetic elements, and genotype-phenotype relationships.

Lower socioeconomic status strengthens the risk of otitis media with effusion after COVID-19 infection: a case-crossover study in Northeast China

Abstract To investigate the associations of otitis media with effusion (OME) with different socioeconomic status (SES) before during and after the coronavirus disease 2019 (COVID-19) outbreak in Northeast China. Three cross-sectional data on daily emergency and outpatient were included pre, during and post COVID-19 epidemic. We recorded the number of OME and symptoms and confirmed SARS-Cov-2 infection in patients with OME. We used logistic regression to evaluate the odds ratio (OR) for OME with COVID-19 infection, and employed an interrupted time series analysis to quantify the effect of COVID-19 outbreak on OME, and a time-stratified case-crossover analysis to evaluate the association of OME with SES before, during and after the COVID-19 outbreak, especially in the two months following the COVID-19 outbreak. During COVID-19 outbreak, the OME significantly increased by 50% (RR: 1.563, 95% CI 1.256–1.942) compared to the same period in other years, low SES was associated with an increased risk of OME, but this low SES-related risk elevation significantly increased during the outbreak of COVID-19, especially in the first month after COVID-19 infection. Individuals under 50 years old were still vulnerable to SES after COVID-19 infection in Liaoning. Lower SES might aggravate OME and greater efforts are needed to improve SES in post-COVID-19.

Aligning climate and air quality goals demands early VOC control for China’s ozone pollution

Abstract Global surface ozone (O 3 ), intensified by climate change, poses increasing health and ecosystem threats. Despite stringent air policies, China’s persistent O 3 pollution exemplifies a global challenge intertwined with climate actions reshaping emission pathways. Optimal mitigation remains contentious, primarily due to inconsistent conclusions regarding the sensitivity of summer regional O 3 formation. Here we show the path dependency in O 3 mitigation strategies for synergistic clean air and climate action goal achievement over multidecade scales. This path dependence is validated by observed concurrent plateaus (2020-2023) in deweathered O 3 concentrations and sensitivity trends across Chinese megacity clusters. Leveraging this understanding of path dependency, we quantitatively reveal that the optimal future strategy involves prioritizing early volatile organic compound reductions, as their high effectiveness for regional O 3 mitigation gradually diminishes towards 2050. This challenges prevailing nitrogen oxides priority paradigms. Our work reframes O 3 control, providing a paradigm for resilient air quality-climate governance.