Browse Articles

Real-world evidence from 50,000 online participants using MoCA-XpressO for cognitive prescreening

Abstract XpressO is a digital cognitive prescreening tool developed by Montreal Cognition (MoCA Test Inc.). In this study, we evaluated real-world online data collected through XpressO in 2024 and early 2025, based on over 50,000 self-enrolled online participants. In line with expectations, we found that the XpressO score—which predicts screening positive for (mild) cognitive impairment—is associated with sex, age, and education. The results indicated that women have a 5.8% [5.3%, 6.3%] lower relative risk of prescreening positive for cognitive impairment, each additional year of age increases the relative risk by 0.59% [0.57%, 0.60%], whereas each year of education decreases the relative risk by 0.99% [0.94%, 1.06%]. We also visualized and quantified interaction effects among these demographic variables as predictors of the XpressO score. While the interaction effect between sex and age was not statistically significant, all other interaction terms, including the three-way interaction between sex, age, and education, were significantly associated with the XpressO score. Additionally, adjusting for demographic factors reduced the observed effect of potential confounders, the language and the platform used. However, when we evaluated a score adjusted for demographics in a clinical cohort of 101 participants, we found that this adjustment slightly but significantly reduced the discriminatory power of the XpressO tool in identifying individuals with cognitive impairment from 0.86 to 0.81. These findings from a real-world online cohort offer novel insights into the complex influence of demographic factors on digital cognitive prescreening. Moreover, they demonstrate that XpressO is a viable tool for online prescreening and can help streamline the diagnostic pathway for individuals who may be eligible for disease-modifying treatments for Alzheimer’s disease.

Long-term effects of forty-hertz auditory stimulation as a treatment of Alzheimer’s disease: Insights from an aged monkey model study

Based mainly on rodents studies, forty-hertz (40-Hz) physical stimulation has been regarded as a potential noninvasive treatment for Alzheimer’s disease (AD). Considering the brain differences between rodents and humans, the effects of 40-Hz physical stimulation need to be further validated using nonhuman primates before its clinical application. Here, we took advantage of a rare opportunity to expose nine aged rhesus monkeys (26 to 31 y old) to 40-Hz auditory stimulation. Given the strong correlation between cerebrospinal fluid (CSF) Aβ and Tau concentrations and corresponding AD pathology in brain parenchyma in clinical practice, we investigated the effects of 40-Hz stimulation on AD pathology by monitoring changes in CSF Aβ and Tau concentrations. Our results revealed that 7 consecutive days of 40-Hz auditory stimulation triggered a rapid and significant increase of Aβ levels by more than 200%, but no effect on Tau levels in the CSF. Additionally, we observed that the elevation of CSF Aβ levels persisted for more than 5 wk after cessation, which had not been reported in any previous studies. After this, a pathological examination of the temporal cortices of 4 of the experimental monkeys was carried out and the data demonstrated that all of them had prevalent extracellular Aβ senile plaque pathology, whereas Tau pathology was negative or very weak. These results provide a good explanation for the differences between the CSF Aβ and Tau protein levels. Together, these first-time results from monkeys suggest that 40-Hz auditory stimulation has strong potential of a noninvasive AD treatment method.

Measuring the molecular origins of stiffness in organic semiconductors

Abstract Mechanical properties of organic molecular semiconductors are determined by a combination of chemical structure and solid-state packing. Measurements of nanoscale mechanical properties on molecular surfaces via atomic force microscopy (AFM) are particularly challenging as the very act of probing how stiff these surfaces are may perturb them, making it difficult to discern subtle differences in stiffness arising from changes in molecular composition. This work presents the first direct, experimental demonstration of the tunability in the nanomechanical properties for a family of molecular semiconductors resulting from systematic alkyl sidechain substitution. While such tunability is intuitively expected, it is a subtle effect that is extremely difficult to detect and quantify reliably from nanoscale AFM measurements due to various spurious force contributions operating on such small length scales. Only after identifying and removing these spurious contributions is the underlying molecular-scale tailoring of mechanical properties observable. Confidence in the measured stiffness trend is reinforced through simulations based on density-functional theory (DFT) and molecular dynamics (MD).

Mechanism and application of reaming anchorage of inverted wedge-shaped hole bottom in argillaceous cemented roadway

Primate gut microbiota induce evolutionarily salient changes in mouse neurodevelopment

Multiple primate species, including humans, evolved brains that are exceptionally large relative to their body sizes. These large brains coevolved with metabolic adaptations that enhance cerebral energy supply, including increased circulating glucose levels. While the gut microbiota (GM) is known to influence host metabolism, its potential role in primate brain evolution remains unclear. To investigate this, we inoculated germ-free mice with the GMs of primate species selected to separate the effects of brain size (encephalization) from phylogenetic relatedness: humans (large-brained, Catarrhini), macaques (smaller-brained, Catarrhini), and squirrel monkeys (large-brained, Platyrrhini). We first show that differences in brain gene expression between mice inoculated with human versus macaque GMs resemble those observed between actual human and macaque brains. Comparing the effects of the different primate GMs on mouse brain gene expression further revealed that despite greater evolutionary distance, the GMs from the two larger-brained species (humans and squirrel monkeys) similarly upregulated genes associated with energy production. Notably, human GMs specifically increased the expression of genes involved in oxidative phosphorylation, and these gene expression changes correlated with increased abundances of GM metabolic pathways related to glucose metabolism and gluconeogenesis. Human GMs also downregulated evolutionarily conserved genes implicated in neurodevelopmental disorders such as autism. Although these are findings based on a small sample of primate species and must be interpreted as preliminary, they suggest that species differences in GM composition can influence brain metabolism and raise the possibility that the GM could have played a supporting role in primate encephalization.

Intranasal unadjuvanted LcrV boosts parental Yersinia OMV primed lung immunity against pneumonic plague in mice

Research on the design of non-destructive assembly and disassembly interference fit for aircraft engines

Sex-allocation trade-offs and their genetic architecture revealed by experimental evolution

The theory of sex allocation is hailed as one of evolutionary biology’s great successes. But while it has successfully predicted strategies of resource allocation to male versus female offspring under a wide range of conditions in species with separate sexes, it has been difficult to verify the fundamental assumption of a direct genetic trade-off between male and female allocations when both sexes are expressed together in the same individuals. This trade-off assumption supposes that mutations that increase an individual’s male allocation reduce its female allocation, and vice versa. Here, we use experimental evolution to generate wide variation in sex allocation in a wind-pollinated annual plant. We demonstrate a clear trade-off between the two sexual functions over time, with populations repeatedly evolving increased male and correspondingly reduced female allocation. Quantitative trait locus (QTL) analysis performed on multiple crosses further reveals the segregation of allelic variation at “trade-off loci.” Taken together, our results demonstrate a genetic trade-off in sex allocation in hermaphrodites and provide compelling evidence for sex-allocation trade-off loci. Our study thus verifies the fundamental assumption of sex-allocation theory and secures its general applicability to both dioecious and hermaphroditic species.

Glassy adhesion dynamics govern transitions between sub-diffusive and super-diffusive cancer cell migration on viscoelastic substrates

Abstract Cell migration is pivotal in cancer metastasis, where cells navigate the extracellular matrix (ECM) and invade distant tissues. While the ECM is viscoelastic, exhibiting time-dependent stress relaxation, its influence on cell migration remains poorly understood. Here, we employ an integrated experimental and modeling approach to investigate filopodial cancer cell migration on viscoelastic substrates and uncover a striking transition from sub-diffusive to super-diffusive behavior driven by the substrate’s viscous relaxation timescale. Conventional motor-clutch based migration models fail to capture these anomalous migration modes, as they overlook the complex adhesion dynamics shaped by broad distribution of adhesion lifetimes. To address this, we develop a glassy motor-clutch model that incorporates the rugged energy landscape of adhesion clusters, where multiple metastable states yield long-tailed adhesion timescales. Our model reveals that migration dynamics are governed by the interplay between cellular and substrate timescales: slow-relaxing substrates prolong trapping, leading to sub-diffusion, while fast-relaxing substrates promote larger steps limiting trapping, leading to super-diffusion. Additionally, we uncover the role of actin polymerization and contractility in modulating adhesion dynamics and driving anomalous migration. These findings establish a mechanistic framework linking substrate viscoelasticity to cell motility, with implications for metastasis and cancer progression.

Regional ventilation–perfusion changes after endobronchial valve therapy assessed by single-photon emission computed tomography in adults with severe COPD

Income insufficiency impacts early brain development in infants facing increased psychosocial adversity: A network-based approach

Early adversity is associated with brain changes that negatively impact development, social-emotional functioning, and academic achievement. The multifaceted nature of adversity complicates efforts to isolate specific factors that affect brain development and developmental outcomes. In the present study, we leverage parent survey data and longitudinal electroencephalography (EEG) data collected from infants during 4-, 9-, and 12-mo well-child visits at a large hospital-based urban primary care clinic serving predominantly low-income families (293 infants, 667 EEGs). Using a network framework, we aimed to identify specific socioeconomic and psychological factors associated with differences in infant brain development. We find that mothers who report to be income insufficient were more likely to have lower educational attainment, report low-income, experience higher levels of stress, and encounter more adverse life events. Controlling for these variables, income insufficiency was specifically associated with delayed brain development in the first year of life; infants developing in a household where parents felt their income was inadequate to support the family’s needs exhibited slower rates of change in alpha peak frequency, alpha power, and beta power. Together, these findings provide a framework of understanding and visualizing how early adversity impacts neurodevelopment and provides evidence for the potential utility of maternal income sufficiency as an additional screening tool to accelerate identification of populations most vulnerable and in need for early intervention.

JWST interferometric imaging reveals the dusty torus obscuring the supermassive black hole of Circinus galaxy

Abstract The dusty and molecular torus is an elusive structure surrounding supermassive black holes, yet its importance is unequivocal for understanding feedback and accretion mechanisms. The torus and accretion disk feed the inspiraling gas onto the active nucleus, launching outflows that fundamentally connect the active nucleus’s activity to the host galaxy. In this work, we utilize the aperture-masking interferometric mode onboard the JWST to achieve a resolution of 0.08" at 4.3 μ m and bring out the fainter features in the central 10 pc of the Circinus galaxy. We show that most of the dust mass is located along the equatorial axis in the form of a 5 × 3 pc disk feeding the active nucleus. Only  < 1% of the dust emission arises from an arc structure composed of hot dust entrained in a molecular and ionized outflow, while the extended emission is associated with dust heated by the active galaxy at large scales.

PEAO: a bio-inspired parallel optimizer with a multi-strategy communication mechanism for breast cancer diagnosis

Deep evolutionary conservation of a sex-determining locus without sequence homology

Sex determination is fundamental to eukaryotic life, yet its molecular basis varies widely across the tree of life. In most animal clades, sex-determining mechanisms are highly diverse and evolve rapidly. Here, we identify an exception in aculeate Hymenoptera, an ancient and diverse clade of haplodiploid insects that includes ants, bees, and stinging wasps. By integrating comparative genomics across Hymenoptera with genetic mapping in bumblebees and hornets, we reveal that the ANTSR locus, a multiallelic noncoding locus, has been maintained for over 150 My as the primary instructive signal for female development. This locus is located in a conserved synteny block that originated at the base of Aculeata and functions as a highly polymorphic, zygosity-based sex determiner, with only heterozygous individuals developing as females across lineages. Despite its deep evolutionary conservation, this sex locus shows no detectable sequence homology among lineages. These findings demonstrate that an essential noncoding locus can retain its function over deep evolutionary time without sequence conservation. More broadly, our results highlight haplodiploid insects as a powerful model for studying the evolution of sex determination mechanisms beyond those linked to sex chromosomes.

Single-shot matrix-matrix photonic processor based on spatial-spectral hypermultiplexed parallel diffraction

Biowaste-grown live microbial feed additive sustainably and significantly cut enteric methane emissions in Indian livestock

Abstract Ruminant enteric methane, the largest agricultural source of CH₄, is a key target in global climate policies. We developed a biowaste-derived live fed microbial (LFM) from fruit- and vegetable residues and evaluated its potential as a scalable intervention to reduce enteric methane while improving animal performance. In controlled in vitro assays and a 98 days in vivo feeding trial in bovine calves ( n  = 15), LFM at 2% dietary inclusion (dry-matter basis) improved feed efficiency by 30.9%, reduced modelled methane emissions by 25.2%, increased total volatile fatty acids by 45.5%, and lowered NH₃–N by 28.4%. At 3% inclusion, feed efficiency improved by 25.5%, methane emissions decreased by 30.4%, total VFA increased by 43.0%, and NH₃–N declined by 11.7%. Methane abatement was estimated by integrating in vitro and in vivo measurements using an empirically fitted conversion factor and Tier-2–compatible intake models. The IPCC (2006) Tier-2 equivalents indicated ~19% reduction. Scaling to India’s livestock herd suggested abatement of 15.4 Mt CH₄ yr⁻¹ (432.3 Mt CO₂-eq yr⁻¹; GWP₁₀₀ = 28) under full adoption, corresponding to ~US$494.1 million annually under the carbon-price assumption used. These findings position biowaste-derived LFM as a circular-economy feed technology capable of simultaneously improving productivity and reducing enteric methane emissions at scale.

Molecular basis of the higher-order assembly of CatSper

CatSper serves as the primary Ca 2+ entry pathway in the principal piece of sperm flagellum and is crucial for sperm motility and fertility. Sperm lacking functional CatSper channels fail to undergo hyperactivation during fertilization, leading to complete male infertility. Along the longitudinal axis of the sperm flagellum, staggered CatSper complexes align in a hand-in-hand arrangement, forming a distinctive quadrilinear zigzag arrays known as CatSper nanodomains. However, the molecular details of how CatSper oligomerizes to form such higher-order assembly remain unclear. In this study, we present the cryoelectron microscopy (cryo-EM) structures of native CatSper dimer (~1.5 MDa) and trimer (~2.3 MDa) megacomplexes, which represent the fundamental units of the zigzag array. We reveal the overall configuration of the zigzag assembly by characterizing the two distinct dimer interfaces that mediate CatSper oligomerization. Specifically, we elucidate the interaction details of two extracellular interfaces formed by CATSPERβ and CATSPERγ at the two dimer interfaces, respectively, and find that CATSPERη, a recently identified component of CatSper, constitutes the transmembrane interface within one of these dimer interfaces. Functional studies in mice demonstrate that CATSPERη is essential for the formation of functional CatSper on the sperm flagellum, and CATSPERη-deficient sperm fail to hyperactivate during fertilization, resulting in male infertility both in vivo and in vitro. Our data provide insights into the higher-order assembly of CatSper at the molecular level, offering clues for the development of male contraceptives.

Mechanical rejuvenation of senescent stem cells and aged bone via chromatin remodeling

Synthesis of 3:2 mullite ceramics from silica-enriched filter cake waste via diphasic gels method

Estimating US savings on outpatient prescription pharmaceuticals from international reference pricing

The exorbitant cost of prescription pharmaceuticals is a critical and long-standing concern facing the United States (US). To curb rising drug costs, international reference pricing, aligning drug prices with those in other high-income countries, has emerged as a prominent policy option. We evaluated the potential national savings from such a strategy in the United States through a comprehensive analysis of utilization patterns and global price differentials for over 8,000 drugs. We project an annual national saving of $184 billion if outpatient prescription pharmaceuticals were priced comparably to those in Canada, France, Germany, Japan, and the United Kingdom. Private insurers, Medicare, and Medicaid would realize savings of 51%, 62%, and 35%, respectively. Pharmaceutical expenditures for common chronic illnesses would be substantially reduced, with costs declining by over 75% for diabetes, atrial fibrillation, and heart failure. Our findings emphasize the substantial fiscal and equity gains achievable through international reference pricing, demonstrating its potential to mitigate financial burdens borne by both healthcare systems and individual patients.