Browse Articles

Depressive symptoms are a key determinant of health-related quality of life in ICU survivors with psychological distress

Abstract Survivors of critical illness frequently experience persistent impairments in health-related quality of life (HRQoL), with psychological symptoms contributing substantially to this burden. The relative contribution of co-occurring depression, anxiety, and post traumatic stress symptoms remains insufficiently understood. To address this gap, we conducted a cross-sectional analysis of pre-randomization data from the PICTURE randomized controlled trial, a multicenter study of a brief primary care–based psychological intervention for post-traumatic stress disorder symptoms following critical illness, including 319 intensive care unit survivors. Clinical, demographic, and mental health assessments were obtained after ICU discharge. Latent profile analysis, random forest modeling, and quantile regression were applied to identify determinants of HRQoL measured by the EuroQol Five-Dimension Five-Level (EQ-5D-5L) index and visual analog scale (VAS). The mean EQ-5D-5L index was 0.71 (SD 0.27; median 0.81) and the mean EQ VAS score was 60.7 (SD 19.4; median 60.0), indicating considerable overall impairment. Depression, anxiety, and post-traumatic stress symptoms showed substantial overlap and formed four distinct symptom profiles associated with specific functional impairments. Screening positive for depression on the 2-item Patient Health Questionnaire (PHQ-2) with ≥ 3 points was associated with a median reduction of -0.13 (95% CI -0.19 to -0.07) on the EQ-5D-5L index and -12.45 points (95% CI -17.93 to -6.96) on the EQ VAS, exceeding clinical and demographic predictors. These findings indicate that depressive symptoms are a major determinant of impaired health related quality of life among intensive care survivors with psychological distress and support routine brief depression screening in post-intensive care follow up. Trial registration: ClinTrials.gov: NCT03315390 (Registration date: 2017-10-20); German Clinical Trials Register: DRKS-ID: DRKS00012589 (Registration date: 2017-10-17).

Electrocatalytic Hotspots in Hierarchical Structures with Ion‐Pump Effect Enable High‐Selectivity Synthesis of 2,5‐Furandicarboxylic Acid From 5‐Hydroxymethylfurfural in Neutral Electrolyte

ABSTRACT The catalytic hotspot effect is a well‐documented phenomenon in photocatalysis, referring to regions with higher catalytic activity at the mesoscale. Whether analogous effect exists in electrocatalysis presents an intriguing question worthy of exploration. In this work, hierarchical NiCo 2 O 4 catalysts with needle‐like, rod‐like, sheet‐like, and bulk‐like morphologies were synthesized and used to explore the hotspot effect in electrocatalysis. The needle‐like hierarchical catalyst demonstrated optimal performance, achieving a 93% yield of 2,5‐furandicarboxylic acid (FDCA) from 5‐hydroxymethylfurfural in neutral electrolyte, comparable to alkaline conditions, while other morphologies yielded less than 40%. In situ Raman spectroscopy revealed that the exceptional catalytic performance stems from a localized high‐pH environment on the surface of the needle‐like catalyst. Finite element simulations reveal that the high pH environment is related to high density of corner sites where the electric field is highly concentrated, resulting in formation of catalytic hotspots. These hotspots can play a role of ion pumps by attracting anions ions which subsequently diffuse into the surrounding regions. The ion pump effect establishes an alkaline local microenvironment which greatly boosts FDCA yield. This work demonstrates that the surface microenvironment of heterogeneous electrocatalysts can be modulated by hotspot engineering, and thus offers a new strategy for catalyst design.

Colorectal cancer incidence before and during the COVID-19 pandemic: a non-linear interrupted time-series analysis

Abstract The COVID-19 pandemic affected healthcare worldwide. This study analysed age-standardised incidence rates (ASIR) of colorectal cancer (CRC) in Bavaria to assess the COVID-19 pandemic’s impact. We modelled CRC ASIR, overall and in the subgroups (sex, age group, site and stage), in the pre-pandemic (01/2007 to 02/2020) and pandemic (03/2020 to 02/2022) periods using interrupted time-series analyses. Predictions for the third year of the pandemic (03/2022 to 02/2023) were compared to expected ASIR. Comparing expected and observed CRC ASIR during the first year of the pandemic showed a significant relative change of -8.8% (95% CI: -12.7% to -4.6%), improving to 1.4% (95% CI: -4.5% to 7.2%) in the third year of the pandemic. Likewise, ASIR significantly decreased across almost all subgroups during the first year of the pandemic, recovering during the second and the third year of the pandemic. Early stages showed a significant estimated reduction, persisting until the third year of the pandemic (-4.7%; 95% CI: -8.6% to -0.9%). In contrast, for women aged 70 years and above and women with colon cancer, ASIR experienced a significant excess. In the first year of the pandemic, estimated CRC ASIR experienced significant decline, returning to the expected rates during the third year of the pandemic, for most, but not all subgroups. The relative difference remained significantly negative for early stages. A significant catch-up effect occurred in the subgroups of women aged 70 years and above and women with colon cancer. Overall, estimations indicate a recovery of CRC ASIR.

Biomimetic Gradient‐Porous Carbon Enables Sustainable High‐Loading Lithium–Sulfur Batteries by Regulating Polysulfide Chemistry

ABSTRACT To realize the commercial viability of lithium–sulfur (Li–S) batteries, it is imperative to substantially increase the areal sulfur loading of the cathode to achieve higher energy density. However, increasing sulfur loading inevitably deteriorates charge‐transport efficiency and slows electrochemical reaction kinetics, leading to pronounced degradation in rate capability and cycling stability. To address these critical challenges, a biomimetic strategy is adopted to engineer gradient‐porous nitrogen‐doped carbon nanomaterials (Bio‐N‐CNTs) with radially graded pore architectures, enabling their use as highly effective sulfur host materials. In situ Raman spectroscopy and DFT reveal that such unique structures facilitate efficient mass transport, ion diffusion, sulfur conversion, and high sulfur loading simultaneously, as well as enable gradient confinement catalytic conversion of LiPSs. As a result, the Bio‐N‐CNT/S cathode exhibits a capacity decay rate of only 0.178% after 100 cycles at a 0.1 C rate. Even under high sulfur loading conditions of 8.6 mg cm −2 , this cathode material maintains 71% capacity retention after 100 cycles. Additionally, a sustainable “precipitation‐enrichment‐reduction‐regeneration” silver recovery strategy with a 93% recovery rate, enhancing economic feasibility. This work demonstrates an innovative, scalable, and sustainable biomimetic Bio‐N‐CNT host for practical Li–S batteries.

Performance of reinforced concrete columns with reduced steel ratios strengthened by hybrid FRP/steel and high-strength concrete systems

Abstract Reinforced concrete (RC) columns with insufficient steel reinforcement present a significant structural concern. This issue is most commonly found in aging buildings, poorly constructed members, or structures designed before the adoption of modern codes. This study investigates the effectiveness of external hybrid strengthening techniques in enhancing the axial load-bearing capacities of such deficient columns. A series of rectangular RC column specimens with intentionally reduced longitudinal reinforcement ratios were tested under axial compression in the laboratory and simulated using ABAQUS software to evaluate structural performance. The specimens were strengthened using a combination of near-surface-mounted (NSM) steel or glass fiber-reinforced polymer bars with externally bonded glass fiber textile mesh covered with different types of high-strength concrete to form a hybrid strengthening solution. The influence of different strengthening configurations on the columns’ ultimate load, energy absorption, and failure modes was evaluated. The results show that the proposed hybrid systems improve the structural behavior of deficient RC columns. They also demonstrate that these systems significantly enhance the structural performance of deficient RC columns, achieving increases in the axial load-bearing capacity ranging from 11% to 78% compared with the deficient specimens. Additionally, the energy absorption capacity improved by up to 382%, highlighting the effectiveness of the combined NSM and external confinement techniques. Furthermore, these systems provide a practical solution for field engineers by helping them strengthen existing structures with inadequate internal reinforcement.

Protective effects of herbal toothpastes against dentin erosion: an in vitro study

Abstract This in vitro study evaluated the protective effects of different herbal and bioactive toothpaste formulations on dentin surfaces exposed to erosive challenges. A total of 96 dentin specimens were prepared from 48 human molars and randomly assigned to six groups ( n  = 16), each receiving one of the following treatments: fluoride-containing toothpaste, clove-containing toothpaste, propolis-containing toothpaste, fluoride combined with nano-hydroxyapatite (F+nHAp), nano-hydroxyapatite toothpaste (nHAp), and casein phosphopeptide–amorphous calcium phosphate (CPP-ACP) based toothpaste. The specimens underwent repeated erosion–brushing–remineralization cycles using 0.01 M hydrochloric acid (pH 1.5) to simulate intrinsic erosive conditions. Surface roughness and microhardness were measured at baseline, after demineralization, and following remineralization. Additional surface characterization was conducted using scanning electron microscopy (SEM) and atomic force microscopy (AFM). All groups showed increased surface roughness after demineralization. However, only the clove group exhibited a significant reduction in roughness after remineralization ( p  < 0.05), returning to baseline levels. Microhardness significantly decreased in all groups following demineralization ( p  < 0.05). After remineralization, only the clove, F+nHAp, and nHAp groups regained microhardness values comparable to baseline ( p  > 0.05). These findings demonstrate that clove-containing, nano-hydroxyapatite-containing, and fluoride+nano-hydroxyapatite toothpaste formulations were the most effective in preserving dentin surface integrity, suggesting their potential role in the prevention of dentin erosion.

Sonographic evaluation of fetal abdominal subcutaneous tissue in pregnancies complicated by gestational and type 1 diabetes mellitus

Comparative analysis of support vector machines, artificial neural network, random forest and gradient boosting for predictive maintenance in mining machinery and equipment: a case study of Chadormalu Iron Ore Mine

A hierarchical multi-agent reinforcement learning framework with high-level guidance from large language models

Abstract Multi-agent reinforcement learning (MARL) has achieved substantial progress in cooperative decision-making, but learning remains difficult in environments with sparse rewards, long decision horizons, and strong inter-agent coupling. Existing methods usually optimize low-level policies directly from numerical observations, which can limit sample efficiency and make it difficult to incorporate structured strategic guidance. Here we propose LEHCA, a hierarchical MARL framework that uses a large language model as a coarse-timescale Commander to provide high-level semantic guidance for value-decomposition-based policy learning. The Commander receives structured textual summaries derived from observable environment information and generates strategic sub-goals, semantic reward-shaping rules, and action-level constraints. These outputs are grounded in low-level QMIX-based agents through two modular mechanisms: semantic reward shaping, which converts abstract sub-goals into dense auxiliary learning signals, and dynamic action masking, which guides exploration toward strategically relevant actions. Experiments on eight StarCraft multi-agent challenge scenarios show that LEHCA improves over QMIX across the evaluated maps in the reported metrics, with larger gains in heterogeneous, sparse-reward, and outnumbered settings. Additional comparisons with QPLEX, MAVEN, and MAPPO on representative scenarios indicate stronger early-stage learning efficiency, while ablation studies and non-LLM control variants show that both hierarchical guidance and LLM-generated semantic reasoning contribute to performance. A lightweight cooperative navigation experiment in the multi-agent particle environment further suggests that the framework can be instantiated beyond StarCraft micromanagement. These results support hierarchical LLM-guided MARL as a promising approach for improving learning efficiency, coordination, and interpretability in cooperative multi-agent systems.

Multicyclic D‐Stereospecific Hydrolase Dimer With High Sustained Activity

ABSTRACT Enzymes are powerful catalysts for selective transformations but often suffer from limited stability under operational conditions such as elevated temperature or the presence of organic cosolvents. While sequence‐based strategies have been widely used to improve stability, chemical protein engineering enables modifications beyond the natural amino acid repertoire thereby offering complementary routes to tailor enzyme function and robustness. Here, we apply the in situ cyclization of proteins (INCYPRO) to a D‐stereospecific hydrolase with low intrinsic thermal stability. Site‐specific macrocyclization substantially improved resilience to heat and cosolvent stress. Unexpectedly, we discovered a cross‐linked protein dimer with enhanced activity and thermal stability. The complex structure was confirmed by x‐ray crystallography. Extending the INCYPRO approach, we engineered a multicyclic enzyme dimer with a total of four cross‐linking sites, which not only retained high activity under benign conditions but also outperformed the wild‐type under stress. Our findings establish protein macrocyclization as a versatile strategy to stabilize both monomeric and multimeric enzymes, providing a powerful route to robust biocatalysts.

Impact of a structured case report on self-reported responses to simulated emergency scenarios: a randomized survey-based study

Abstract Case reports are a long-standing component of medical research, but their association with self-reported responses to simulated clinical scenarios remains underexplored. This study investigated whether exposure to a structured case report influences simulated emergency medical decisions. This randomized survey-based study was conducted among licensed physicians between March and May 2025. Participants were randomly assigned to an intervention group, which received a structured case report on blunt neck trauma, or a control group, which did not. Both groups subsequently provided self-reported Likert-scale responses to identical simulated emergency scenarios, covering five domains: local trauma consequences, accompanying injuries, diagnostic methods, airway management strategies, and hospital selection. Responses were collected on Likert scales. Group differences were assessed using Mann–Whitney U tests, t-tests, and chi-squared tests; prespecified exploratory subgroup analyses examined the moderating role of clinical experience. Sixty-three participants completed the study. Baseline demographics and qualifications did not differ significantly between groups. Exposure to the case report was associated with statistically significant differences in self-reported responses to simulated scenarios, with the most pronounced associations in airway management strategies (all five items statistically significant, median effect size r = 0.44). Intervention participants assigned higher ratings to maintaining spontaneous breathing and supraglottic airway use, while assigning lower appropriateness to endotracheal intubation and cricothyrotomy. Moderate associations were observed in diagnostic choices (e.g., pathological breath sounds, ultrasound use) and hospital selection (e.g., ECMO availability). No consistent effects were found for local or accompanying injuries. Exploratory stratified analyses revealed that junior physicians (≤ 5 years of practice) appeared more responsive, with significant differences across multiple domains and larger effect sizes (median r > 0.6). In contrast, no statistically significant between-group differences were detected in the senior (> 15 years) subgroup, although this exploratory analysis was limited by small subgroup size. Structured case reports may influence self-reported responses to simulated emergency scenarios, particularly among less experienced clinicians. These findings suggest that the educational impact of case-based learning formats may vary depending on the level of clinical experience, but do not allow conclusions about real-world clinical behavior or patient outcomes. Future work should further investigate adaptive case report formats and their potential integration into emergency medicine training. Trial registration : German Clinical Trials Register (DRKS00038961), registered von 13 January 2026.

Characterization of newly identified N–S shear zones in the Egyptian Nubian Shield by integrating geophysical, remote sensing and field data

Abstract This study provides a comprehensive analysis of the large-scale north-south (N-S) shear zones in the Egyptian Nubian Shield (ENS), a critical segment of the East African Orogen. Integrating aeromagnetic, gravity, remote sensing, and field-based structural data, the study delineates the geometry, kinematics, and tectonic significance of these N-S shear zones and their interaction with other major tectonic features, such as the Najd Fault System and the Keraf suture. The ENS is subdivided into compressional, transpressional, and extensional domains, each characterized by distinct structural regimes and evolutionary histories. Within the Central Transpressional Domain, the Najd Fault System (NFS) creates a complex network of NW-SE-trending sinistral strike-slip shear zones intersected by NE-SW-directed dextral shear zones, forming a conjugate shear system. Key large-scale N-S-trending shear zones in the ENS include the Safaga-Shalul, Wadi Kareim-Umm Bisilla, Um Gheig-Nugrus, Barramiya-Mueilha, Abu Swayel-Muqsim, and Himitrah-Madari shear zones. The structural evolution of the ENS comprises five main deformational phases. D1 features N-S shortening, resulting in thrust imbrication and E-W-trending foliations. D2 is marked by NE-SW-directed shortening and NW-trending sinistral shearing, characterized by large-scale sinistral shear zones. The Najd Fault System (620-540 Ma) dominates the Central Transpressional Domain. D3 is characterized by E-W shortening and N-S dextral shearing, leading to the formation of N-S transpressional shear zones and folds (600-590 Ma) that affect all rock units except post-tectonic granites. D4 features N-S-oriented dextral shear zones that affect E-W, NW-SE, and N-S structural fabrics within transpressional belts. Red Sea rifting reactivated these zones, transforming them into brittle, sinistral strike-slip faults that affect all rock units. The NW-SE, N-S, and NE-SW-oriented shear zones in the ENS form a conjugate system linked to the activity of the Najd Fault System. Geophysical data indicate that these shear zones likely extend subsurface, connecting to the extensive N-S-striking shear zones in the Nubian Shield. The Keraf shear zone developed contemporaneously with the NFS, suggesting a link to the genesis of the N-S dextral shear zones.

Free transverse vibration analysis of Non-uniform Nano-Timoshenko beams rotating around two perpendicular axes using differential quadrature method

Abstract This research examined the vibrational characteristics of nano-rotors using Timoshenko beam theory, Eringen’s non-local elasticity theory, and gyroscopic effects. The governing equations and boundary conditions for whirling analysis were formulated for a nano-rotor with a non-uniform cross-section revolving around two orthogonal axes. The equations were converted to a non-dimensional form by introducing dimensionless parameters and then solved numerically using the differential quadrature technique. Numerical results validated the precision and convergence of the proposed solution. The findings indicate that, in the absence of rotation, the forward and backward vibration frequencies of the nano-rotor were similar. Nevertheless, once the rotor began rotating along its longitudinal axis, this symmetry was compromised. The forward frequencies increased, whilst the backward frequencies decreased. The frequency divergence became more pronounced with increasing rotational velocity, leading to higher critical velocities. Besides rotational effects, structural characteristics considerably influenced the vibrational response. Augmenting the shaft radius elevated both forward and backward frequencies, as well as critical velocities, illustrating that geometric alterations may be used to optimize rotor dynamics. Moreover, non-local elasticity increased the scale-dependence of phenomena. Increasing non-local parameters marginally increased the frequencies of the first vibration mode, while substantially decreasing those of higher modes, highlighting the nanoscale dependence of vibrational properties. The research indicated that the changes in the rotor’s diameter profile significantly affected its vibrational characteristics. A more pronounced drop in diameter along the rotor’s length increased first-mode frequencies and critical velocities, while diminishing those of higher modes. A greater rotor diameter increased the frequency difference between forward and backward modes, underscoring the significance of geometric design in regulating vibrational properties.

Formal Allylic C(sp ³ )−H Carboxylation With CO ₂ via Copper Metallaphotoredox Catalysis

ABSTRACT Catalytic carboxylation of ubiquitous C─H bonds with CO 2 has been demonstrated as a sustainable and streamlined pathway to valuable carboxylic acids. However, the catalytic carboxylation of abundant allylic C(sp 3 )─H bonds with CO 2 , which presents a unique opportunity to synthesize structurally diverse 3‐butenoic acids, still remains challenging. Herein, we report the first copper metallaphotoredox‐catalyzed formal allylic C(sp 3 )─H carboxylation with CO 2 , enabling efficient and selective synthesis of 3‐butenoic acids under mild and redox‐neutral conditions. This strategy lies in combining highly reducing photocatalysts to generate alkene radical anion intermediates with copper catalysis to orchestrate regioselective elimination, providing a distinct pathway from traditional allylic C(sp 3 )─H functionalization via forming allyl‐metal intermediates. This method features high atom and step economy, broad substrate scope, good functional group tolerance, facile scalability, and easy access to valuable compounds, including diverse bioactive molecules, natural products, and 13 C‐labeled anti‐inflammatory drug sulindac.

Dorsal switch protein 1 activates toll immune signaling pathway via modular serine protease in Tenebrio molitor

Effect of biomass management strategies on carbon and nitrogen supply in legume and legume–grass mixtures under organic arable farming

The STK11 gene F354L mutation is associated with male spermatogenic dysfunction

Abstract To investigate the probability of the STK11 gene F354L mutation in normal individuals and infertile males with spermatogenic dysfunction, and to predict its impact on male spermatogenic function. We analyzed the F354L coding sequence in 192 azoospermia and severe oligozoospermia patients (patient group) and 199 normal fertile males (control group) using PCR and DNA sequencing. We detected 16 cases of the mutation in the patient group, but 7 cases were also found in the control group. The mutation rate showed some significant statistical difference between the two groups ( p  = 0.043). Immunofluorescence staining revealed that STK11 is highly expressed in mouse testicular tissues and localized to the midpiece of human and mouse sperm. Lentivirus-mediated overexpression of wild-type and F354L-mutant STK11 in TCAM2 cells demonstrated that the F354L variant reduces AMPK phosphorylation and disrupts cellular polarity, as evidenced by Western blot and Golgi reorientation assays. These findings suggest that the F354L mutation may impair spermatogenesis and sperm motility by perturbing metabolic homeostasis and cell polarity.

Integrating single-cell and bulk transcriptomic analyses to explore key lactylation-related genes in benign prostatic hyperplasia

Abstract Benign prostatic hyperplasia (BPH) is a prevalent age-related disorder characterized by chronic inflammation, metabolic dysregulation, and abnormal cellular proliferation. Protein lactylation, an emerging post-translational modification closely associated with cellular metabolism, has been implicated in the pathogenesis of various diseases. However, its role and associated molecular features in BPH remain uncharacterized. We integrated publicly available single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq datasets derived from BPH and normal prostate tissues. Utilizing machine learning algorithms (LASSO, Random Forest, and Boruta) strictly as feature selection tools, we identified key lactylation-related candidate genes. Subsequently, employing the BPH-1 cell line in vitro, we preliminarily investigated the potential biological functions of the prioritized epithelial target, ANXA2, through siRNA-mediated knockdown, Western blotting, ELISA, and cell proliferation assays. We computationally identified ANXA2 and IFI27 as key lactylation-related candidate genes, both of which were significantly downregulated in BPH tissues. scRNA-seq data revealed their cell-type specificity, demonstrating that ANXA2 is predominantly expressed in epithelial cells, whereas IFI27 is primarily expressed in endothelial cells. Furthermore, we uncovered a potential link between metabolism and inflammation involving ANXA2. Specifically, ANXA2 knockdown in BPH-1 cells was associated with alterations in glycolytic gene expression and a concomitant reduction in lactate production. Our data suggest that this decreased lactate level is associated with elevated secretion of the proinflammatory cytokine IL-6 and enhanced cellular proliferation. Additionally, cellular trajectory and communication analyses indicated that ANXA2⁺ epithelial cells and IFI27⁺ endothelial cells represent distinct subpopulations characterized by enhanced intercellular signaling capacities, suggesting their potential roles as critical molecular hubs within the BPH microenvironment. This study presents the first single-cell resolution landscape of lactylation-related gene activity in BPH. We computationally identified ANXA2 and IFI27 as key lactylation-related candidate genes. Importantly, our study suggests a potential link whereby ANXA2 deficiency is associated with BPH cell proliferation and potential metabolic and inflammatory alterations. These findings provide valuable new insights into the underlying pathophysiological mechanisms of BPH and lay the groundwork for the development of targeted therapeutic strategies.

External validity of deep learning solution for spontaneous intracranial hemorrhage detection on head CT scans

Morphological and pomological diversity of fig (ficus carica l.) germplasm in North-Western India