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SHPRH together with the Ube2D family of enzymes directly ubiquitinates PCNA at Lys164 in vitro

Ubiquitin-chain attachment to a highly conserved Lys164 residue in the proliferating cell nuclear antigen (PCNA) signals for template switching events to resume stalled DNA replication. In human cells, the reaction is catalyzed by the ubiquitin ligases SNF2 histone linker PHD RING helicase (SHPRH) or helicase like transcription factor (HLTF), together with the Ubc13-Mms2 ubiquitin conjugating enzyme complex. The reaction requires mono-ubiquitinated PCNA as the substrate. Here, we provide biochemical evidence that SHPRH also directly ubiquitinates unmodified PCNA at Lys164. The reaction requires the Ube2D family of ubiquitin conjugating enzymes and robustly ubiquitinates both free and DNA-bound PCNA. We further found that efficient PCNA ubiquitination requires SHPRH’s HIRAN domain, which mediate interactions with PCNA. Our data suggest another layer of regulation of DNA damage responses through PCNA ubiquitination.

AI speeds up design of devices that turn waste heat into electricity

The role of protein quality in designing sustainable food systems

Increased serum albumin corrected anion gap levels are associated with poor prognosis in sepsis-induced coagulopathy patients

Background Sepsis-induced coagulopathy (SIC) is associated with high mortality, and acid-base disturbances are common in critically ill patients with this condition. The anion gap (AG) is affected by serum albumin levels, suggesting that the albumin-corrected anion gap (ACAG) may serve as a more accurate prognostic marker. However, the relationship between ACAG and outcomes in SIC remains unclear. Methods This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (2008–2019). Adult patients (≥18 years) diagnosed with SIC within 24 hours of ICU admission were enrolled. SIC was defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria combined with Sequential Organ Failure Assessment (SOFA) scores. ACAG was calculated as: ACAG = AG + 2.5 × (4.4 – Albumin [g/dL]). The optimal cutoff value (17.7 mmol/L) was determined using X-tile software. The primary outcome was in-hospital 30-day all-cause mortality. Time-dependent Cox proportional hazards models, Kaplan-Meier (KM) analysis, and receiver operating characteristic (ROC) curves were performed. Subgroup and interaction analyses were conducted to assess effect modification by malignancy status. Results A total of 3,846 patients were included (mean age 64.8 years; 38.4% female). Non-survivors exhibited significantly higher ACAG levels than survivors (median [IQR]: 21.4 [18.5–24.8] vs. 17.6 [15.2–20.3] mmol/L, P  < 0.001). KM analysis showed that high ACAG (≥17.7 mmol/L) was associated with significantly lower in-hospital 30-day survival (log-rank P  < 0.001). In the time-dependent Cox model (adjusted for SOFA, SAPS II, and lactate), high ACAG was independently associated with increased mortality (HR = 3.04, 95% CI: 1.88–4.91, P  < 0.001). ACAG demonstrated superior discrimination compared to uncorrected AG (AUC: 0.633 vs. 0.620, DeLong test P  < 0.001). Notably, a significant interaction was observed between ACAG and malignancy ( P for interaction < 0.001), with ACAG showing stronger predictive value in non-malignant patients (HR = 3.60, P  < 0.001) than in those with cancer (HR = 1.59, P  = 0.477). Conclusions Elevated ACAG is independently associated with increased in-hospital 30-day mortality in SIC patients and outperforms uncorrected AG. Its calculation requires no additional cost or testing, making it a practical bedside risk stratification tool, particularly for non-malignant patients.

Four rising stars shaping the future of cancer research

Multivariate Birnbaum-Saunders accelerated lifetime regression model: estimation and residual analysis

Seroprevalence and altitude-dependent patterns of Toxoplasma gondii infection in livestock from northern Armenia

Toxoplasmosis, caused by the intracellular protozoan parasite Toxoplasma gondii , is a zoonotic disease affecting almost all warm-blooded vertebrates. Despite its importance to both humans and animals, research on toxoplasmosis in Armenia has been limited, with a notable 35-year gap in studies focused on host animals. This study aimed to conduct a survey of T. gondii seroprevalence among livestock in Armenia. A total of 1996 serum samples of sheep, pigs, and cattle were collected from the northern provinces (Shirak, Lori, Tavush) of Armenia and screened by the ELISA test for the presence of total anti- Toxoplasma IgG and IgM antibodies. In the present study, the overall seroprevalence of T. gondii in livestock from northern Armenia was 15.5% (308/1,982; 95% CI: 14.0–17.2). The overall prevalence of infection among sheep was 22.5% (196/870; 95% CI: 19.8–25.5), pigs 28.6% (4/14; 95% CI: 8.4–58.1), and cattle 10.1% (112/1,112; 95% CI: 8.4–12.0). After excluding pigs due to insufficient sample size, a Pearson’s chi-square test demonstrated a strong and statistically significant association between host species and T. gondii infection status (χ² = 58.31, df = 1, p < 0.001). To investigate environmental determinants of infection, species-specific logistic regression models were fitted using temperature and elevation as continuous predictors. In cattle, none of the environmental variables showed statistically significant associations with seropositivity, and model fit did not improve over the null model. In contrast, sheep displayed a strong and non-linear relationship between seropositivity and elevation. The likelihood of infection decreased from low to mid altitudes and rose slightly at the highest elevations. Temperature showed no detectable effect in either species. These findings reveal clear species-specific differences in environmental sensitivity and highlight elevation as a key ecological factor shaping T. gondii exposure risks in sheep.

Inline monitoring of cold forging processes using vibration sensors

Abstract Multi-stage cold forging processes are used for the mass production of particularly resistant metal products of different level of geometrical complexity. These processes also allow a high degree of dimensional accuracy to be achieved, which can eventually exempt the formed parts from a subsequent machining treatment and therefore lower the overall production costs. Improving the robustness of cold forging processes via digitisation requires the integration of different types of sensors into the manufacturing system. However, the compactness and high geometric precision of the tool, dictated by the high loads involved during the process, and the constraints related to the quality of the final formed part, represent considerable challenges. In this context, externally attachable sensors such as vibration sensors offer a unique perspective. Therefore, this study explored the application of vibration sensors for monitoring cold forging processes. The investigated scenario involved a tool designed for the production of screw-like parts in two stages, comprising a forward rod extrusion and an upsetting stage. Different sensors with inline monitoring capabilities were attached at various locations within the manufacturing system and their recorded signals were analysed, focusing on the interdependence between the part quality, the tool load and the press activity. The results showed that vibration sensors can be used not only for a global monitoring of the press behaviour but also for the local monitoring of the tool load and the quality of the final formed part.

Are routinely collected clinical and sociodemographic characteristics associated with social functioning and activities of daily living in schizophrenia? A machine learning approach descriptive of a schizophrenia cohort

Patients with schizophrenia often experience substantial impairments in social functioning and activities of daily living (ADLs). Previous studies have highlighted links between sociodemographic and clinical factors and daily life functioning. However, routinely collected, non-scale-based clinical and sociodemographic characteristics have rarely been systematically evaluated as a standalone predictive framework. Understanding whether such variables alone can inform functional outcomes in schizophrenia may have important implications for public health. Using the French multicentric psychosocial rehabilitation database REHABase, we predicted five dimensions of the Social Autonomy Scale (a validated, clinician-administered questionnaire widely used in France): personal care, basic ADLs, financial autonomy, complex ADLs, and social and affective relationships. We used a SuperLearner ensemble machine learning method with a large set of routinely collected socio-demographic and basic clinical predictors descriptive of schizophrenia patients. Our sample comprised 948 participants. Averaged R2 on hold-out testing sets were higher for basic ADLs (mean R2: 0.35) than for social and affective relationships (0.16), financial autonomy (0.14), complex ADLs (0.13), and personal care (0.01). Factors associated with improved functioning included: being in a relationship, higher education, lower Clinical Global Impression scores, higher Global Assessment of Functioning scores, living in personal housing, being employed, mid-range illness duration, a history of suicide attempts and psychiatric comorbidities. Our findings indicate an association between socio-demographic and standard clinical variables routinely assessed in practice and outcomes in social functioning and ADLs. However, these variables account for only a limited proportion of the observed variance. This underscores the need for more specialized and precise assessments, e.g., based on cognitive abilities, to better understand and address patient functioning. We recommend targeted interventions focused on improving clinical symptoms, housing conditions, and supporting employment. Finally, clinicians should not assume that patients with seemingly protective factors, such as shorter illness duration, or absence of comorbidities, do not require further support.

Research on mechanism and control technique of floor heave in deep soft rock roadway at Banji Coal Mine

Abstract Aiming at the severe floor heave occurring at the machine head section of the belt conveyor downhill roadway in the 1105 mining area of Banji Coal Mine, Bozhou, Anhui, a systematic investigation was conducted using mechanism analysis, numerical simulation, and on-site industrial testing to elucidate the multifactorial mechanism and control technique of floor heave in deep soft rock roadways. The dominant factors contributing to roadway floor heave were identified as high horizontal tectonic stress, weak floor lithology, high water content in the floor strata, and deficiencies in the original support system. Subsequently, the loosening zone of the roadway floor was detected, and the development characteristics of floor plastic deformation and deformation concentration were analyzed in detail. On this basis, the reasonable effective depth for grouting reinforcement was determined. Accordingly, an integrated floor heave control technique combining deep-hole high-pressure grouting and drainage was proposed to reinforce and strengthen the roadway structure. A numerical model was then established to comparatively analyze roadway deformation over a three-month period under conditions with and without reinforcement. The results indicated that the overall stress state of the surrounding rock was significantly improved after reinforcement, leading to effective control of floor heave deformation, while deformation of the roof and sidewalls was simultaneously mitigated. Furthermore, on-site monitoring results demonstrated that 30 d after grouting, floor subsidence, inwardconvergence of the two sides, and floor heave of the roadway all reduced quickly, and the deformation gradually stabilized. These findings confirm that the proposed floor heave control technique can effectively suppress deformation of the roadway surrounding rock and ensure safe and stable operation.

Correction: Critical risk identification in construction projects using 2D and 3D risk matrices

Design of natural frequency solution method based on the lateral disturbance modeling of slurry discharge pipelines in slurry shield machines

Abstract This study applies classical fluid-structure interaction (FSI) principles to analyze the lateral deflection and natural frequency of slurry discharge pipelines in slurry shield machines. By idealizing the pipeline as an infinitely long cylinder supported by equally spaced rigid rings and adopting the Euler-Bernoulli beam theory and classical fluid-structure interaction principles, the control differential equation considering the interaction between the pipeline and the flowing slurry was adapted for the tunneling environment. This model incorporates the dynamic coupling between symmetrical and asymmetrical vibration modes driven by slurry flow velocity and Coriolis force. Through analytical solutions and numerical methods, the natural frequencies and mode shapes were determined. The results show that the slurry flow will reduce the natural frequencies and may lead to system instability at high flow rates. The accuracy of the model was verified by using the measured data from the site of the South-to-North Water Diversion Project in Beijing, China, spanning four different geological strata. The relative error ranged from 1.58 to 6.29%. The results highlight the dominance of low-order modes and demonstrate that the true engineering value lies in predicting how geological conditions and slurry impurities significantly influence the pipeline’s dynamic behavior, providing guiding suggestions for the engineering design and vibration control of similar systems.

PDGFRα-positive mesenchymal stem/stromal cells contribute to autonomous vascular formation through in-body tissue architecture

Driven by endogenous platelet-derived growth factor receptor α (PDGFRα)-positive cells, in-body tissue architecture (iBTA) enables the autonomous formation of vascularized tissues within subcutaneously implanted molds, overcoming the limitations of traditional cell therapies. The cellular mechanisms were investigated in PDGFRα reporter mice. Recruited PDGFRα-lineage cells were closely associated with Pecam-1-positive vessels and often adopted perivascular positions. Flow cytometry revealed that these cells expressed the mesenchymal stem/stromal cell (MSC) markers (CD73, CD90, and CD105). Additionally, the cultured isolates maintained MSC morphology and demonstrated osteogenic, chondrogenic, and adipogenic differentiation potential in vitro. The approach was successfully scaled to a porcine model, which exhibited organized tissue maturation, including vascular structures and collagen deposition, within 2 weeks. iBTA eliminates the need for cell isolation and immunosuppression by leveraging resident PDGFRα-positive MSCs for in situ tissue generation, providing a direct pathway for autologous vascular tissue engineering applications.

Early-onset cancer fuels calls for wider screening — but at what cost?

Compression and bending performance of novel 3D printed mixed-star negative Poisson’s ratio metamaterials using CCD-based optimization and finite element analysis

Abstract Auxetic structures, recognized for their lightweight design, auxeticity, and exceptional mechanical properties, have garnered considerable attention from the engineering sector. The auxeticity and associated mechanical traits of these structures depend on the negative Poisson’s ratio (NPR) principle. These structures comprise a collection of repetitive unit cells, the size of which is crucial for achieving the desired performance. This study introduces a high-performing auxetic structure based on a unit cell named Mixed Star and optimizes its performance using a hybrid statistical-numerical approach. Considering the length, height, thickness, and inclination of the wall as cell parameters, a detailed test plan was generated through a statistical approach. A series of mixed-star Metamaterial (MSM) structures were modeled according to the Design of Experiment plan, and their mechanical performance, specifically energy absorption, modulus, and strength in compression and bending, was evaluated using a validated FEM model. The collected results were analyzed, revealing key effects along with their nature. In-depth analysis of the findings indicated that the auxetic behavior of the structure is closely associated with the size of its unit cell, highlighting the need for an optimized cell size to enhance structural performance. By applying an appropriate approach, the optimum cell size was determined while considering both compression and flexural loads, resulting in substantial gains in auxeticity and mechanical performance, depending on the response parameter and loading condition. This study emphasizes the potential of a hybrid statistical-numerical approach in optimizing the geometry of NPR structures to achieve superior performance, providing a valuable framework and paving the way forward for future research.

Beyond silos: Drivers and barriers to intersectoral collaboration in zoonotic disease surveillance and response in the Greater Accra Metropolitan Area, Ghana

The One Health approach has gained global traction as a strategy to combat zoonotic diseases, which account for 60–75% of emerging infectious diseases. While effective surveillance requires intersectoral collaboration, challenges such as fragmented systems, resource constraints, and weak coordination hinder efforts, particularly in low- and middle-income countries like Ghana. This qualitative study explores the factors influencing collaboration in zoonotic disease surveillance and response at the operational level, providing insights to strengthen intersectoral collaboration and improve public health outcomes across human, animal and wildlife sectors. Using reflexive thematic analysis, we analyzed interviews with 66 professionals from the human, animal, and wildlife health sectors, all directly involved in zoonotic disease surveillance and response. The findings reveal individual factors (interpersonal relationships, personal initiative, motivations, professional hierarchy, shared interests) and structural factors (financial resources, workforce availability, the governance and organization of surveillance and response systems, institutional visibility, knowledge systems) that shape collaboration dynamics. Additionally, positive outcomes from past collaborations created reinforcing cycles that influenced future engagement. Participants shared expectations of improved efficiency, strengthened disease surveillance, and enhanced resource pooling from future collaboration. Despite the global push for intersectoral collaboration, operational-level challenges persist. While grounded in a Ghanaian context, the types of factors identified likely resonate across resource-limited settings, though their specific manifestations and relative importance may vary by context. These findings underscore the broader need for stronger governance, equitable partnerships, and realistic alignment of stakeholder expectations to foster sustainable One Health collaboration and enhance zoonotic disease surveillance globally.

Proprioceptive judgements made with the hand and the jaw: two distinct but functionally related body parts

Impact of age and clinical factors on the feasibility of mobile digital monitoring in people at risk of suicide

Objective Assessing the risk of suicidal outcomes is challenging, particularly in older people. Smartphone-based digital phenotyping may help to monitor suicide risk through ecological momentary assessment (EMA) applications. In this real-world study, we investigated if age and other clinical factors were associated with participation in EMA at baseline, and with retention in EMA monitoring among patients at risk of suicide. Methods Participation in EMA was determined by quantifying the installation of the MEmind mobile application in individuals involved in the SmartCrisis 1.0 and 2.0 studies. The patients were followed-up over a 6-month period. Results N = 512 patients met inclusion criteria, of which 387 installed the MEmind application on their smartphone. While age as a continuous variable was not associated with using EMA at baseline, being aged older than 50 and being engaged in an intimate relationship were independently associated with longer participation in EMA (OR 2.070, 95%CI [1.054–4.066], and OR 2.103, 95%CI [1.076–4.110], respectively). In an exploratory survival analysis, we found that EMA retention increased with age (p < 0.001). Conclusion Feasibility of EMA seems warranted in older people at risk of suicide. Clinicians should be encouraged to offer EMA monitoring to older adults, as they commonly face limitations in their access to healthcare facilities.

Why more fossil fuels won’t fix the Iran energy crisis

Material characterization of stone surfaces in the inner chambers of the Khufu (Cheops) Pyramid: towards informed conservation strategies

Abstract This study presents a systematic material characterization of the Queen’s and King’s Chambers stone surfaces of the Khufu Pyramid, conducted within the framework of the ScanPyramids mission. The two chambers show distinct interactions with their environment due to their differing lithologies. In the Queen’s Chamber, halite was identified as the main phase responsible for efflorescence on the massive limestone blocks. In the King’s Chamber, kaolinization of granite minerals appears to drive salt efflorescence formation in the upper blocks. Importantly, this research reports the first in situ application of X-ray fluorescence imaging for the characterization of Aswan granite. By mapping elemental distributions and correlating them with mineralogical phases, a completely non-destructive analysis of the granite surfaces was possible. In addition, a chemometric approach is proposed as an alternative to imaging for mineral-phase differentiation based on spot measurements. The study demonstrates how in situ portable non-destructive (contact-free) methods, combined with targeted micro-sampling, provide critical insights into deterioration mechanisms and support preventive conservation strategies for one of the world’s most iconic monuments.