Browse Articles

Estradiol and vitamin D exert a synergistic effect on preventing osteoporosis via the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway

Abstract This study aimed to investigate the antiosteoporotic effects and regulatory mechanisms of estradiol (E2) and vitamin D. MC3T3-E1 cells were treated with E2, vitamin D, or their combination, followed by a systematic assessment of cell proliferation and osteogenic differentiation capacity across the treatment groups. Subsequently, miRNA sequencing was performed to analyze differentially expressed miRNAs between the control and E2&vitamin D groups. The target relationship between miR-351-5p and IRS1 was validated, and the effects of the miR-351-5p/IRS1 axis on osteogenesis and mTOR/NFκB signaling pathway were determined after combination treatment. Additionally, an ovariectomized (OVX) osteoporosis mouse model was established to ‌systematically examine‌ the effects of E2, vitamin D, and their combination on osteoporosis and mTOR/NFκB signaling pathway. E2 and vitamin D synergistically promoted MC3T3-E1 cell proliferation and osteogenic differentiation. miR-351-5p was identified through miRNA sequencing analysis. miR-351-5p was downregulated in MC3T3-E1 cells after E2 and vitamin D combination treatment, and its overexpression partially reversed the effect of the combination treatment on osteogenesis. IRS1 was a target of miR-351-5p. When overexpressed, IRS1 partially mitigated the impact of miR-351-5p overexpression on osteogenesis and mTOR/NFκB signaling pathway under the combination treatment. Furthermore, in vivo experiments demonstrated that E2 and vitamin D could synergistically prevent osteoporosis in OVX mice by inhibiting the mTOR/NFκB signaling pathway. In conclusion, E2 and vitamin D exhibited a synergistic effect in preventing osteoporosis through the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway. E2 and vitamin D combination treatment could be a potential anti-osteoporotic strategy for osteoporosis treatment.

Retraction: Automatic structural scene digitalization

Decoding the impact of aging on the interaction between visual attention and working memory

Mine fire emergency path planning based on hybrid strategy improved WOA algorithm

To address the challenge of personnel evacuation during mine fires, an enhanced Whale Optimization Algorithm (WOA) incorporating a hybrid strategy inspired by the intelligent behavior of marine life is proposed and applied to mine escape route planning. Initially, to overcome the limitations of the original WOA—such as poor optimization accuracy, susceptibility to local optima, and slow convergence—five improvement strategies are introduced: Sobol sequence for population initialization, nonlinear time-varying factors, adaptive weighting, stochastic learning, and Cauchy mutation. These enhancements are compared against single-strategy improved WOAs.Subsequently, path planning simulations were conducted using several extracted algorithms and grid-based methods. The results demonstrate that the optimal path length achieved by the Multi-Strategy WOA (MSWOA) is 41.7% shorter than that of the standard WOA, 42.3% shorter than WOA-1, and 48.5% shorter than PSO for the shortest path. Additionally, the average path length of MSWOA is 32.2% shorter than WOA, 40.5% shorter than WOA-1, and 41.4% shorter than PSO. The MSWOA algorithm generates the shortest and smoothest path among the tested methods.Based on the analysis of the path graph and iteration frequency graph, it is recommended to apply the MSWOA algorithm to path planning experiments. The findings indicate that the WOA with the five integrated strategies significantly enhances optimization accuracy and convergence speed, making it a robust solution for mine evacuation route planning.

Computational molecular characterization of a novel SLC20A2 variant associated with primary familial brain calcification

Numerical study on the biomechanics mechanism of Type II endoleak after EVAR for Abdominal Aortic Aneurysm

Type II endoleak, a common complication following Endovascular Aneurysm Repair (EVAR), remains a leading cause of re-intervention, yet its biomechanical mechanisms are not fully understood. This study employed an idealized model of the aneurysmal sac, Inferior Mesenteric Artery (IMA), and Lumbar Arteries (LAs) to explore endoleak mechanisms using Computational Fluid Dynamics (CFD) and Fluid-structure Interaction (FSI) simulations. The results demonstrated that pressure differences between the sac and branch arteries drive Type II endoleak, with the IMA often serving as the primary inlet. Under the influence of Type II endoleak, flow disturbances near the IMA and LAs suggest potential challenges in thrombus formation. Comparative analysis between CFD and FSI showed that CFD overestimated peak flow velocity in the IMA and underestimated sac pressure, while also displaying a temporal lag in velocity and pressure curve throughout the cardiac cycle. These findings indicate that CFD is suitable for rapid assessments where precision is less critical, whereas FSI is more appropriate for detailed mechanistic studies. This work clarifies the biomechanics of Type II endoleak and underscores the importance of selecting appropriate numerical methods in clinical and research contexts.

Computable phenotypes to identify respiratory viral infections in the All of Us research program

Abstract Electronic health records (EHRs) contain rich temporal data about respiratory viral infections, but methods to identify these infections from EHR data vary widely and lack robust validation. We developed computable phenotypes by integrating virus-specific International Classification of Diseases (ICD) billing codes, prescriptions, and laboratory results within 90-day episodes. Analysis of 265,222 participants with EHR data from the All of Us Research Program yielded national cohorts of varied size: large cohorts for SARS-CoV-2 ( n  = 28,729) and influenza ( n  = 19,784); medium cohorts for rhinovirus, human coronavirus, and respiratory syncytial virus ( n  = 1,161-1,620); and smaller cohorts for the other viruses ( n  = 238–486). Using laboratory results as a reference standard, phenotypes using virus-specific ICD codes and medications had variable sensitivity (8–67%) but high positive predictive value (PPV, 90–97%) for most viruses, while influenza virus and SARS-CoV-2 phenotypes had lower PPV (69–70%) that improved with the inclusion of additional ICD codes. Identified infections exhibited expected seasonal patterns matching CDC data. This integrated approach identified infections more effectively than individual components alone and demonstrated utility for severe infections in hospital settings. This method enables large-scale studies of host genetics, health disparities, and clinical outcomes across episodic diseases, with flexibility to optimize sensitivity or PPV depending on the specific research question.

Spatial mapping and determinants of intimate partner violence among married women in Sierra Leone: A cross-sectional study

Background Intimate partner violence is a pervasive public health and human rights issue, disproportionately affecting women worldwide. In Sierra Leone, where gender inequalities and socio-cultural norms remain entrenched, intimate partner violence is a significant concern, with severe consequences for women’s physical, emotional, and social well-being. Understanding the spatial distribution and determinants of intimate partner violence is crucial for designing targeted interventions to address this issue. Using data from the 2019 Sierra Leone demographic and health survey, this study explored the geographic patterns of intimate partner violence and identified key socio-demographic and behavioural factors associated with its prevalence among married women. Methods The study employed data from the 2019 Sierra Leone demographic and health survey. The study comprised of 3,611 married women between the ages of 15 and 24. Spatial autocorrelation and Moran’s I statistic were employed to analyse the spatial distribution of intimate partner violence. The study utilised mixed-effect multilevel binary logistic regression using a four-model framework to determine the factors related to intimate partner violence. The findings were presented as adjusted odds ratios (aOR) and a 95% confidence interval (CI). Results The study revealed an overall intimate partner violence prevalence of 56%, with physical violence accounting for 38.2%, sexual violence for 6.2%, and emotional violence for 45.9% among married women in Sierra Leone. Hotspot districts for intimate partner violence were identified in the Western area (urban and rural areas) and the Northwestern province (Kambia and Karene). At the same time, Bo, Kenema, and Bombali, the provincial headquarters of the Northern, Eastern, and Southern provinces, were found as cold spot districts for intimate partner violence. Factors associated with intimate partner violence included married women aged 25–29, those with one-two partner controlling behaviour, and those who provided one-two justifications for wife beating. Furthermore, married women exposed to interparental violence and those who resided in the Northwestern, Northern, and Western area had a higher likelihood of experiencing intimate partner violence. Conclusion The high prevalence of intimate partner violence, particularly in hotspot districts like the Western and Northwestern province, underscore the need for province-specific interventions to protect women and reduce violence. Efforts should focus on challenging harmful cultural norms that justify wife-beating and controlling behaviours while also addressing the intergenerational cycle of violence by supporting women exposed to interparental violence. Policies must prioritise targeted education, community engagement, and enforcement of laws against intimate partner violence. Integrating intimate partner violence prevention into broader health, social, and legal systems is essential to ensure a coordinated and sustainable response to this pervasive issue.

Clinico-genomic study reveals association of dengue virus genome high frequency mutations with dengue disease severity

Abstract Transmission of the dengue virus (DENV) places a huge burden on public health in several endemic regions. Like other RNA viruses, mutations in the DENV genome greatly governs its virulence, transmissibility, and interaction with the host immune system. Present study focuses on integrated analysis of mutation and clinical data accompanied at the onset of dengue fever. The findings from the associated clinical data with the variants of the DENV are critical for early detection of the disease and understanding the disease progression. RNA was isolated from the 1310 serum samples collected from the NS1-antigen positive dengue patients. Serotyping reveals that DENV-2 was predominant in circulation. The genome of 1305 DENV-2 was sequenced using Oxford Nanopore Technology and Illumina platforms. A total of 1023 DENV-2 demonstrated > 50% genome coverage. Mutation analysis across the 1023 DENV-2 genomes yielded a total of 2667 mutations including 627 non-synonymous and 2040 synonymous mutations. We observed a notable over-representation of synonymous mutations in prM and ancC genes while a higher occurrence of non-synonymous mutations was found in ancC, prM, and M proteins. Comparison of mutation frequency between mild and severe demonstrates higher mutation frequency in severe phenotype. Moreover, we observed a total of 56 significant mutations including 23 in severe, 17 in moderate and 16 in mild. The E-protein having non-synonymous mutations were docked with DC-SIGN with lower binding energy (ΔG = − 11.9 kcal/mol) for severe as compared to mild (ΔG = − 13.5 kcal/mol), suggesting lesser affinity of E-protein and DC-SIGN in case of severe as compared to the mild. We have identified the core set of high frequency mutations significantly associated with distinct dengue disease severity viz., mild, moderate and severe. Furthermore, in-silico protein modelling and docking studies demonstrate the potential functional role of the non-synonymous mutations identified across E-protein in severe dengue.

Functional dynamic prosthesis alignment maintained across varying footwear using a modular prosthetic ankle-feet system

Changing footwear often presents a challenge for lower extremity prosthesis users. When prosthesis alignment is completed by the Certified Prosthetist, the prosthetic foot is set at an angle accommodating a single shoe heel rise (shoe heel height minus forefoot height); deviation from this heel rise causes misalignment of the prosthesis. To address this problem, the Rehabilitation & Engineering Center for Optimizing Veteran Engagement & Reintegration (RECOVER) has developed a modular ankle-feet system allowing for the use of footwear of varying heel rises without the need for realignment by the prosthesis user. The primary aim of this study was to understand if clinically acceptable prosthesis alignment is maintained as prosthesis users change between modular foot-shoe sets. Three women transtibial prosthesis users self-selected three pairs of footwear with a heel rise up to 10 cm. Using the modular prosthetic ankle-feet system, participants completed five walking trials per foot-shoe set in the motion analysis laboratory. Reflective markers were used to track the location of the prosthetic socket during walking. These data in combination with center of pressure measurements were used to calculate ankle-foot-shoe rollover shapes and the location of the origin of the best-fit circle for each rollover shape. The locations of the resulting best-fit circle origins indicate prosthesis alignment is maintained within clinically acceptable parameters as users change between foot-shoe sets. These findings have implications for improving footwear options for people with lower-extremity amputations.

Overfishing and sea warming drive the collapse of Paracentrotus lividus

Abstract As a seafood delicacy, the purple sea urchin Paracentrotus lividus is the most exploited echinoid species in the Mediterranean Sea, with a significant increase in total catches being reported over the last 2 decades. This work presents: (i) the findings from two demographic monitoring campaigns, conducted on P. lividus populations in summer 2023, at shallow depths within the coastal areas of Sicily and Apulia; (ii) a meta-analysis of the P. lividus density in the Mediterranean Sea over the last 30 years. In both sampled areas, the recorded individual density was lower than ever, with an average value of 0.2 ind/m2. No significant difference in P. lividus density was detected between protected and non-protected areas. The observed rarity of the edible sea urchin is corroborated by a meta-regression analysis of data from 44 published articles over the period 1990–2020, showing that the decline of P. lividus populations in the Mediterranean Sea began in 2003, coincident with the occurrence of a pan-European heat wave and with the anomalous warming of the entire Mediterranean Sea.

Divergent impacts of quantity versus price-based monetary policies on banking systemic risk: Evidence from China

This study investigates the effects of price-based (PMP) and quantity-based monetary policies (QMP) on systemic risks within China’s banking sector. We identify exogenous components of PMP and QMP by isolating explicit structural shocks in a structural vector autoregression model. Systemic risks are categorized into bottom-up risks, which assess how the distress or default of a single bank can contribute to systemic vulnerabilities, and top-down risks, which evaluate the likelihood of a bank experiencing distress during financial market turbulence. Utilizing a smooth local projection model, we analyze the impact of PMP and QMP on these two types of systemic risks. Our findings reveal that contractionary PMP shocks exacerbate bottom-up systemic risks while mitigating top-down risks. In contrast, contractionary QMP shocks initially elevate but subsequently diminish bottom-up risks, with minimal impact on top-down risks. Importantly, PMP affects state and non-state banks differently, decreasing top-down risks in state banks but increasing them in non-state banks. This differential impact indicates that the risk-taking behavior of non-state banks triggered by contractionary PMP can spill over, amplifying the damage of financial distress for both state and non-state banks.

Experimental analysis of the damping characteristics of longmaxi shale under graded cyclic loading with different confining pressures

Scaling-up coral reef carbonate production: Sea-urchin bioerosion suppresses reef growth in Hawaiʻi

Coral reefs provide essential social, economic, and ecological services for millions of people worldwide. Yet, climate change and local anthropogenic stressors are damaging reefs globally, compromising their framework-building capacity and associated functionality. A reef carbonate budget provides a quantitative measure of growth and functional status, but utilization of remote sensing to scale-up such a metric remains limited. This study used census-based field surveys across depths in Hōnaunau Bay, Hawaiʻi to examine rates of carbonate production, and scaled-up estimates across the bay with high-resolution benthic-cover data derived from airborne imaging spectroscopy. Average net carbonate production was ~0.5 kg CaCO3 m-2 y-1 across the 2–17 m depth gradient, ranging from -2.1 to 2.4 kg CaCO3 m-2 y-1 at 3 and 6 m, respectively. The scaling model with the lowest root mean square error was achieved using a 2-m resolution map of live coral cover. Sea-urchin densities averaged 51 individuals m-2, which were among the highest recorded densities on coral reefs globally. The subsequent high bioerosion from sea urchins suppressed estimated reef-growth potential, particularly in the shallow reef <6 m. Field estimates of net carbonate production translate to vertical reef accretion of ~0.5 mm y-1 across depths, indicating the reef in its present form is not keeping pace with the current rate of sea-level rise (3.55 mm y-1) in west Hawaiʻi. These results suggest a need for improved fisheries management in Hōnaunau Bay to enhance carnivorous-fish abundances, thereby helping to reduce sea-urchin densities and improve reef-growth capacity. Critically, an estimated threshold of ~26% live coral cover is currently needed to maintain positive net production across depths. This study demonstrates the utility of monitoring carbonate production by integrating field measurements and airborne imaging spectroscopy, and highlights the need for management decisions in west Hawaiʻi that enhance resilient carbonate budgets of coral reefs.

Street level urban metabolism as a tool for mapping urban flows in Amman’s neighborhoods

Abstract This article examines urban systems through the analytical framework of street-level urban metabolism, expanding upon Kennedy’s multi-layered studies of urban metabolic processes. While traditional urban metabolism analyzes cities as macro-scale systems, this study focuses on neighborhood street networks as critical units of resource flow, applying Kennedy’s indicator framework to a finer-grained assessment of streets as metabolic conduits. Focusing on Amman, Jordan, the study dissects seven key metabolic flows (e.g., water, energy, waste) at the street level, adapting methodologies from Rotterdam’s neighborhood-scale metabolic analysis. This approach reveals how hyper-localized flows interact with environmental stressors such as water scarcity, extreme heat, and limited green infrastructure. By comparing four distinct typical neighborhoods in the city, the study identifies disparities in flow efficiency tied to urban design, offering targeted strategies to enhance resilience. The research’s goal is to generate actionable strategies for enhancing urban infrastructure by mapping resource flows and proposing interventions. Ultimately, aiming to develop a scoring system that quantifies the impact of each flow within cities studied, and complemented by a survey to understand the local’s perspective to identify analytically, flows and elements that enhance the city’s metabolism and environmental stresses.

Clinical characteristics and optical coherence tomography findings in epiretinal membrane, macular pseudohole, epiretinal membrane-foveoschisis, and lamellar macular hole

Purpose To evaluate the optical coherence tomography (OCT) findings of epiretinal membrane (ERM) and its three associated diseases: macular pseudohole (MPH), ERM-foveoschisis (ERM-FS), and lamellar macular hole (LMH). Methods We retrospectively reviewed all eyes that underwent vitrectomy with a follow-up of at least 6 months. All eyes were classified into four groups, ERM, MPH, ERM-FS, and LMH based on spectral-domain (SD) OCT findings. Factors analyzed included preoperative and postoperative best-corrected visual acuity (BCVA), presence of inner and outer retinal cysts, epiretinal proliferation (EP), and ellipsoid zone (EZ) disruption, central fovea thickness (CFT), central retina thickness (CRT), and macular volume (MV). Results After enrolling 720 eyes of 664 patients, eyes were classified into four groups: ERM (592 eyes), MPH (76 eyes), ERM-FS (63 eyes), and LMH (42 eyes). BCVA significantly improved in all groups. Although preoperative BCVA was not significantly different among the four groups, postoperative BCVA was significantly worse in LMH versus ERM (p < 0.001). Inner and outer retinal cysts were significantly more prevalent in ERM-FS versus ERM and the other three groups, respectively. EP was significantly more frequently observed in LMH versus the other three groups (p < 0.001). CFT and CRT were significantly higher in ERM versus the other three groups, and MV was significantly larger in ERM than in MPH and LMH (p < 0.05). Conclusion ERM had a higher CFT and CRT, and a larger MV. The postoperative BCVA was worse in LMH versus ERM, while LMH had a higher frequency of EP.

Speed up integer-arithmetic-only inference via bit-shifting

Recipe for Flat Bands in Pyrochlore Materials: A Chemist’s Perspective

Association of high-sensitivity C-reactive protein to albumin ratio with all-cause and cardiac death in coronary heart disease individuals: A retrospective NHANES study

Background This research aimed to explore the association of high-sensitivity C-reactive protein to albumin ratio (CAR) with death events in community-based patients with coronary heart disease (CHD). Methods 624 CHD participants were followed for 36 months using data from the 2015–2018 National Health and Nutrition Examination Survey (NHANES). The CAR was dichotomized at 0.075 mg/g to stratify inflammation levels. Relationships between CAR, high-sensitivity C-reactive protein (hsCRP), albumin (ALB) and all-cause and cardiac death in all participants and subgroups were analyzed using restricted cubic spline (RCS), Kaplan-Meier survival curves and Cox proportional hazards models. Results Both CAR and hsCRP showed positive correlations with all-cause and cardiac death risk while ALB exhibited a U-shaped correlation with all-cause death risk but a negative correlation with cardiac death risk. The high-CAR group had higher risks of all-cause (P = 0.04) and cardiac death (P = 0.02). The hazard ratios (HR) (95% confidence intervals (CI)) for all-cause death was 1.77 (1.15–2.74) (P = 0.010), while it was 2.99 (1.44–6.22) (P = 0.003) for cardiac death. No significant interaction was observed in subgroup analyses. Conclusions A CAR threshold of 0.075 mg/g effectively distinguished between high and low inflammation risks. Elevated CAR significantly increased the risk of all-cause and cardiac death in community CHD patients.

In situ mineral formation on a plate for direct and efficient screening of bacteria suitable for biocementation