Search Results (2,473)

Background: Immune checkpoint inhibitor therapy in patients with lung cancer and metastatic melanoma is associated with exacerbation of autoimmune-related diseases. The efficacy of treatment targeting the programmed cell death receptor-1 (PD-1) checkpoint relies upon a feedback loop between interferon gamma (IFN-γ) and the interleukin-12 isoform, IL-12p40. Paradoxically, both cytokines and the anti-PD-1 antibody worsen psoriasis. We previously reported an immunomodulating peptide, designated IK14004, that inhibits progression of Lewis lung cancer in mice yet uncouples IFN-γ from IL-12p40 production in human immune cells. Methods: Immune cells obtained from healthy donors were exposed to IK14004 in vitro to further characterise the signalling pathways affected by this peptide. Using C57BL/6 immunocompetent mice, the effect of IK14004 was tested in models of lung melanoma and psoriatic skin. Results: Differential effects of IK14004 on the expression of IFN-α/β, the interleukin-15 (IL-15) receptor and signal transducers and activators of transcription were consistent with immune responses relevant to both cancer surveillance and immune tolerance. Moreover, both melanoma and psoriasis were inhibited by the peptide. Conclusions: Taken together, these findings suggest mechanisms underlying immune homeostasis that could be exploited in the setting of cancer and autoimmune pathologies. Peptide administered together with checkpoint blockers in relevant models of autoimmunity and cancer may offer an opportunity to gain further insight into how immune tolerance can be retained in patients receiving cancer immunotherapy. Full article

CareCoach seeks to enhance self-efficacy in family caregivers of people living with dementia and has been feasibility tested in a multicentre randomised controlled trial. The intervention offers two face-to-face sessions with a trained coach and access to an online platform with nine modules. This paper reports findings from an embedded qualitative process evaluation assessing implementation from the implementer’s (‘coach’s’) (n = 8) perspective using individual interviews and implementer group discussions. Qualitative data were transcribed verbatim, inductively coded and analysed using Normalisation Process Theory. Implementers demonstrated (1) ‘Coherence’ by seeking to understand how CareCoach compared to current practice, highlighting the importance of supporting coaches to differentiate and identify boundaries between their new ‘coach role’ and usual practice; (2) ‘Cognitive Participation’ by reviewing training and resources to understand their role own responsibilities and facilitate delivery of coaching sessions; group supervision and peer support were also emphasised; (3) ‘Collective Action’ through interactions with carers to deliver key behavioural aspects such as goal setting, problem solving, and providing feedback; and (4) ‘Reflexive Monitoring’ by appraising the intervention to gain useful insights that could facilitate refinement of CareCoach training and delivery. This study provides a theoretically informed understanding of the implementation of CareCoach for caregivers of people living with dementia and provides recommendations to enhance training for coaches, intervention delivery and carer engagement. Full article

As the penetration of intermittent renewable energy sources continues to increase, ensuring reliable power system and frequency stability is of importance. Battery energy storage systems (BESSs) have emerged as an important solution to mitigate these challenges by providing essential grid support services. In this context, a state-of-charge (SOC)-frequency control strategy for grid-forming BESSs is proposed to enhance their role in stabilizing grid frequency and improving overall system performance. In the system, the DC-link capacitor is regulated to maintain the angular frequency through a matching control scheme, emulating the characteristics of the rotor dynamics of a synchronous generator (SG). Thereby, the active power control is implemented in the control of the DC/DC converter to further regulate the grid frequency. More specifically, the relationship between the active power and the frequency is established through the SOC of the battery. In addition, owing to the inevitable presence of differential operators in the control loop, a high-gain observer (HGO) is employed, and the corresponding parameter design of the proposed method is elaborated. The proposed strategy simultaneously achieves frequency regulation and implicit energy management by autonomously balancing power output with available battery capacity, demonstrating a novel dual benefit for sustainable grid operation. To verify the effectiveness of the proposed control strategy, a 0.5-Hz frequency change and a 10% power change are carried out through simulations and also on a hardware-in-the-loop (HIL) platform. Full article

In the context of urban decarbonization, multi-energy microgrids (MEMGs) are gaining increasing relevance due to their ability to enhance synergies across multiple energy vectors. This study presents a block-based MILP framework developed to optimize the operations of a real MEMG, with a particular focus on accurately modeling the structure of electricity and natural gas bills. The objective is to assess the added economic value of integrating a battery energy storage system (BESS) under the assumption it is employed to provide implicit flexibility—namely, bill management, energy arbitrage, and peak shaving. Results show that under assumed market conditions, tariff schemes, and BESS costs, none of the analyzed BESS configurations achieve a positive net present value. However, a 2 MW/4 MWh BESS yields a 3.8% reduction in annual operating costs compared to the base case without storage, driven by increased self-consumption (+2.8%), reduced thermal energy waste (–6.4%), and a substantial decrease in power-based electricity charges (–77.9%). The performed sensitivity analyses indicate that even with a significantly higher day-ahead market price spread, the BESS is not sufficiently incentivized to perform pure energy arbitrage and that the effectiveness of a time-of-use power-based tariff depends not only on the level of price differentiation but also on the BESS size. Overall, this study provides insights into the role of BESS in MEMGs and highlights the need for electricity bill designs that better reward the provision of implicit flexibility by storage systems. Full article

Although evidence suggests adiposity as a modifiable risk factor for postmenopausal breast cancer (BC), its association with premenopausal BC remains uncertain. This potential differential relationship for menopausal status has been insufficiently investigated in the Moroccan population due to limited data. This study aims to assess the relationship between various indicators of adiposity and the risk of BC among Moroccan women by menopausal status. A multicenter case-control study was conducted in Morocco between December 2019 and August 2023, including 1400 incident BC cases and 1400 matched controls. Detailed measures of adiposity and self-reported measures from different life stages were collected. Unconditional logistic regression analyses were conducted to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between body size indicators and the risk of BC, adjusting for a range of known risk factors for BC. Higher waist circumference (WC) and hip circumference (HC) were associated with an increased risk of BC in both pre- (p-trend < 0.001 for both WC and HC) and post-menopausal women (p-trend < 0.001 for WC, 0.002 for HC). Current body mass index (BMI) ≥30 kg/m² increased the risk of postmenopausal BC (p-trend = 0.012). Among postmenopausal women, higher weight at age 20 was positively associated with BC risk (p-trend < 0.001), while, weight at age 30 was significantly associated with increased BC risk in both pre- (p-trend = 0.008) and post-menopausal women (p-trend = 0.028). Interestingly, weight gain since age 20 was inversely associated with BC risk in postmenopausal women in the adjusted model (p-trend = 0.006). Young-adult BMI observed a significant increased trend with BC risk in both pre- (p-trend = 0.008) and post-menopausal women (p-trend < 0.001). In premenopausal women, larger body shape during childhood and early adulthood was positively associated with BC risk (p-trend = 0.01 and = 0.011, respectively). In postmenopausal women, larger childhood and adolescent body silhouettes were also associated with increased BC risk (p-trend = 0.045 and 0.047, respectively). These results suggest that anthropometric factors may have different associations with pre- and post-menopausal BC among Moroccan women. This underscores the importance of conducting large prospective studies to better understand these findings and explore their links to different molecular subtypes of BC. Full article

The fungal component of microbiota, known as the mycobiome, inhabits different body niches such as the skin and the gastrointestinal, respiratory, and genitourinary tracts. Much information has been gained on the bacterial component of the human microbiota, but the mycobiome has remained somewhat elusive due to its sparsity, variability, susceptibility to environmental factors (e.g., early life colonization, diet, or pharmacological treatments), and the specific in vitro culture challenges. Functionally, the mycobiome is known to play a role in modulating innate and adaptive immune responses by interacting with microorganisms and immune cells. The latter elicits anti-fungal responses via the recognition of specific fungal cell-wall components (e.g., β-1,3-glucan, mannan, and chitin) by immune system receptors. These receptors then regulate the activation and differentiation of many innate and adaptive immune cells including mucocutaneous cell barriers, macrophages, neutrophils, dendritic cells, natural killer cells, innate-like lymphoid cells, and T and B lymphocytes. Mycobiome disruptions have been correlated with various diseases affecting mostly the brain, lungs, liver and pancreas. This work reviews our current knowledge on the mycobiome, focusing on its composition, research challenges, conditioning factors, interactions with the bacteriome and the immune system, and the known mycobiome alterations associated with disease. Full article

Breeding programs often overlook the use of root traits. Therefore, we investigated the relevance of sorghum root traits in explaining its adaptation to combined drought and heat stress (CDHS). Six (i.e., three pre-release lines + three checks) sorghum genotypes were established at two low-altitude (i.e., <600 masl) locations with a long-term history of averagely very high temperatures in the beginning of the summer season, under two management (i.e., CDHS and well-watered (WW)) regimes. At each location, the genotypes were laid out in the field using a randomized complete block design (RCBD) replicated two times. Root trait data, namely root diameter (RD), number of roots (NR), number of root tips (NRT), total root length (TRL), root depth (RDP), root width (RW), width–depth ratio (WDR), root network area (RNA), root solidity (RS), lower root area (LRA), root perimeter (RP), root volume (RV), surface area (SA), root holes (RH) and root angle (RA) were gathered using the RhizoVision Explorer software during the pre- and post-flowering stage of growth. RSA traits differentially showed significant (p < 0.05) correlations with grain yield (GY) at pre- and post-flowering growth stages and under CDHS and WW conditions also revealing genotypic variation estimates exceeding 50% for all the traits. Regression models varied between pre-flowering (p = 0.013, R² = 47.15%, R² Predicted = 29.32%) and post-flowering (p = 0.000, R² = 85.64%, R² Predicted = 73.30%) growth stages, indicating post-flowering as the optimal stage to relate root traits to yield performance. RD contributed most to the regression model at post-flowering, explaining 51.79% of the 85.64% total variation. The Smith–Hazel index identified ICSV111IN and ASAREACA12-3-1 as superior pre-release lines, suitable for commercialization as new varieties. The study demonstrated that root traits (in particular, RD, RW, and RP) are linked to crop performance under CDHS conditions and should be incorporated in breeding programs. This approach may accelerate genetic gains not only in sorghum breeding programs, but for other crops, while offering a nature-based breeding strategy for stress adaptation in crops. Full article

Sustainability in the construction sector has become a fundamental objective for mitigating escalating environmental challenges; given that concrete is the most widely used man-made material, extending its service life is therefore critical. Among durability concerns, magnesium sulfate (MgSO₄) attack is particularly deleterious to concrete structures. Therefore, this study investigates the short- and long-term performance of concrete produced with copper slag (CS)—a massive waste generated by copper mining activities worldwide—employed as a supplementary cementitious material (SCM), together with recycled coarse aggregate (RCA), obtained from concrete construction and demolition waste, when exposed to MgSO₄. CS was used as a 15 vol% cement replacement, while RCA was incorporated at 0%, 20%, 50%, and 100 vol%. Compressive strength, bulk density, water absorption, and porosity were measured after water curing (7–388 days) and following immersion in a 5 wt.% MgSO₄ solution for 180 and 360 days. Microstructural characteristics were assessed using scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric analysis with its differential thermogravimetric derivative (TG-DTG), and Fourier transform infrared spectroscopy (FTIR) techniques. The results indicated that replacing 15% cement with CS reduced 7-day strength by ≤10%, yet parity with the reference mix was reached at 90 days. Strength losses increased monotonically with RCA content. Under MgSO₄ exposure, all mixtures experienced an initial compressive strength gain during the short-term exposures (28–100 days), attributed to the pore-filling effect of expansive sulfate phases. However, at long-term exposure (180–360 days), a clear strength decline was observed, mainly due to internal cracking, brucite formation, and the transformation of C–S–H into non-cementitious M–S–H gel. Based on these findings, the combined use of CS and RCA at low replacement levels shows potential for producing environmentally friendly concrete with mechanical and durability performance comparable to those of concrete made entirely with virgin materials. Full article

Background: Adhesive capsulitis (AC) causes a global limitation of both active and passive range of motion (ROM) in the shoulder, with or without pain, and no specific radiographic findings. Its course is self-limiting and progresses through three or four stages. The diagnosis is primarily clinical, since imaging tests are nonspecific. Treatment options include physical therapy (PT), intra-articular corticosteroid injections, suprascapular nerve block (SSNB), and hydrodilatation (HD). The latter is useful for expanding and reducing inflammation of the joint capsule through the insufflation of saline solution, anesthetics, and corticosteroids. Objectives: To compare whether patients with AC, stratified by phase 1 and 2, who receive high-volume HD as treatment achieve better outcomes in terms of shoulder pain and function compared to patients who receive low-volume HD. To compare whether there are differences in PT times and to determine mean axillary recess (AR) values. Methods: A randomized, parallel-block, triple-blind clinical trial will be conducted in 64 patients with AC in phases 1 and 2, aged 30 to 70 years, with limited active and passive ROM in two planes, and shoulder pain lasting more than 3 months. HD will be administered with volumes of 20 mL or 40 mL, followed by a conventional rehabilitation program. Outcomes will be reviewed at the 1st, 3rd, and 6th months of HD. Variables collected will include Shoulder Pain and Disability Index (SPADI), Visual Analog Scale (VAS), Range of motion (ROM), Lattinen index (LI), AR size, and time to completion of PT. Results: HD has been gaining clinical relevance in interventional rehabilitation as a treatment for AC, although its medium- and long-term efficacy remains a matter of debate. The variability in the volumes used for capsular expansion, with studies ranging from 18 mL to 47 mL, is compounded by the fact that most of these studies do not differentiate between AC stages. This could influence treatment effectiveness. Furthermore, diagnosis remains a challenge since valid and specific diagnostic parameters are lacking. Conclusions: Understanding the differences between HD techniques, considering the influence of certain factors such as the volume used or the stages of AC, as well as improving diagnosis and the coordination of scientific work. This could facilitate the development of protocols for the use of HD in AC. Full article

In recent years, significant progress has been made in breast reconstructive surgery, particularly with the use of three-dimensional (3D) disassemblable scaffolds. Reconstructive plastic surgery aimed at restoring the shape and size of the mammary gland offers medical, psychological, and social benefits. Using autologous tissues allows surgeons to recreate the appearance of the mammary gland and achieve tactile sensations similar to those of a healthy organ while minimizing the risks associated with implants; 3D disassemblable scaffolds are a promising solution that overcomes the limitations of traditional methods. These constructs offer the potential for patient-specific anatomical adaptation and can provide both temporary and long-term structural support for regenerating tissues. One of the most promising approaches in post-mastectomy breast reconstruction involves the use of autologous cellular and tissue components integrated into either synthetic scaffolds—such as polylactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL)—or naturally derived biopolymer-based matrices, including alginate, chitosan, hyaluronic acid derivatives, collagen, fibrin, gelatin, and silk fibroin. In this context, two complementary research directions are gaining increasing significance: (1) the development of novel hybrid biomaterials that combine the favorable characteristics of both synthetic and natural polymers while maintaining biocompatibility and biodegradability; and (2) the advancement of three-dimensional bioprinting technologies for the fabrication of patient-specific scaffolds capable of incorporating cellular therapies. Such therapies typically involve mesenchymal stromal cells (MSCs) and bioactive signaling molecules, such as growth factors, aimed at promoting angiogenesis, cellular proliferation, and lineage-specific differentiation. In our review, we analyze existing developments in this area and discuss the advantages and disadvantages of 3D disassemblable scaffolds for mammary gland reconstruction, as well as prospects for their further research and clinical use. Full article

Reparative tertiary dentinogenesis requires the recruitment and odontogenic differentiation of dental pulp stem cells (DPSCs). Extracellular vesicles (EVs) as bioactive molecules have gained attention in regenerative medicine for their ability to mediate tissue repair through intercellular communication, influencing cell recruitment, proliferation, and differentiation. This study aimed to evaluate the effects of EVs on DPSC homing and odontogenic differentiation for dentin regeneration. DPSC-derived EVs were cultured in either growth (EV-G) or odontogenic differentiation (EV-O) conditions and isolated using a modified precipitation method. EVs were characterized by nanoparticle tracking analysis, scanning electron microscopy, antibody array, and cellular uptake assay. Treatment with 5 × 10⁸ EVs/mL significantly enhanced DPSC chemotaxis and proliferation compared with a no-treatment control and a lower dosage of EV (5 × 10⁷ EVs/mL). Gene expression and biochemical analyses revealed that EV-O up-regulated odontogenic markers including collagen type 1A1 (COL1A1), runt-related transcription factor 2 (RUNX2), and alkaline phosphatase (ALP). EV-O enhanced dentin regeneration by approximately 55% over vehicle controls in a rabbit partial dentinotomy/pulpotomy model. We identified key microRNAs (miR-21-5p, miR-221-3p, and miR-708-3p) in EV-O involved in cell homing and odontogenesis. In conclusion, our EV-based cell homing and odontogenic differentiation strategy has significant therapeutic potential for dentin regeneration. Full article

The model explicitly incorporates boundary conditions that account for the complex interplay between sections experiencing varying degrees of reduction. This interaction significantly influences the overall deformation behavior and force loading. The control effect is associated with boundary conditions determined by the unevenness of the compression, which have certain quantitative and qualitative characteristics. These include additional loading, which is less than the main load, which implements the process of plastic deformation, and the ratio of control loads from the entrance and exit of the deformation site. According to this criterion, it follows from experimental data that the controlling effect on the plastic deformation site occurs with a ratio of additional and main loading in the range of 0.2–0.8. The next criterion is the coefficient of support, which determines the area of asymmetry of the force load and is in the range of 2.00–4.155. Furthermore, the criterion of the regulating force ratio at the boundaries of the deformation center forming a longitudinal plastic shear is within the limits of 2.2–2.5 forces and 1.3–1.4 moments of these forces. In this state, stresses and deformations of the plastic medium are able to realize the effects of plastic shaping. The force effect reduces with an increase in the unevenness of the deformation. This is due to a change in height of the longitudinal interaction of the disparate sections of the strip. There is an appearance of a new quality of loading—longitudinal plastic shear along the deformation site. The unbalanced additional force action at the entrance of the deformation source is balanced by the force source of deformation, determined by the appearance of a functional shift in the model of the stress state of the metal. The developed theory, using the generalized method of an argument of functions of a complex variable, allows us to characterize the functional shift in the deformation site using invariant Cauchy–Riemann relations and Laplace differential equations. Furthermore, the model allows for the investigation of material properties such as the yield strength and strain hardening, influencing the size and characteristics of the identified limit state zone. Future research will focus on extending the model to incorporate more complex material behaviors, including viscoelastic effects, and to account for dynamic loading conditions, more accurately reflecting real-world milling processes. The detailed understanding gained from this model offers significant potential for optimizing mill roll designs and processes for enhanced efficiency and reduced energy consumption. Full article

Background/Objectives: Enriched oral nutritional supplementation (ONS) has been shown to increase muscle mass in cancer patients. This study aims to identify the immunomodulatory effects and predictive biomarkers associated with this intervention. Methods: The soluble levels of 92 immune- and oncology-related mediators were determined before and after an intervention (8 weeks) in 28 patients with cancer receiving either a standard (n = 14) or an enriched ONS (n = 14) using the Olink proteomics analysis pipeline (Olink^® Target 96 Immuno-Oncology panel (Uppsala, Sweden)) Results: Patients receiving enriched ONS experienced an average weight gain of 1.4 kg and a muscle mass increase of 2.2 kg after 8 weeks, both statistically significant (p < 0.05), while no such improvements were observed in the standard ONS group. Inflammatory markers TRAIL and LAMP3 were significantly reduced, along with an increase in Gal-1, suggesting lower inflammation and enhanced myogenic differentiation. However, patients who failed to gain muscle mass with the enriched formula showed a more aggressive inflammatory profile, characterized by higher serum levels of soluble MUC16, ARG, and IL12RB1. Interestingly, muscle mass gain could be predicted before the intervention, as responders had lower baseline levels of PGF, CD28, and IL12RB1. These differences were specific to recipients of the enriched ONS, confirming its immunomodulatory effects. Conclusions: Our findings support the use of enriched oral nutritional supplementation (ONS) as an effective strategy not only to enhance caloric and protein intake but also to promote anabolism and preserve muscle mass in cancer patients. The identification of immune profiles suggests that specific biomarkers could be used to predict which patients will benefit most from this type of intervention. This may allow for the implementation of personalized immunonutrition strategies that optimize resource allocation and improve clinical outcomes, particularly in vulnerable populations at risk of cachexia. Full article

Background: Neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), are increasingly recognized as conditions arising from multifaceted interactions among genetic predisposition, environmental exposures, and epigenetic modifications. Among epigenetic mechanisms, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and PIWI-interacting RNAs (piRNAs), have gained attention as pivotal regulators of gene expression during neurodevelopment. These RNA species do not encode proteins but modulate gene expression at transcriptional and post-transcriptional levels, thereby influencing neuronal differentiation, synaptogenesis, and plasticity. Objectives: This systematic review critically examines and synthesizes the most recent findings, particularly in the post-COVID transcriptomic research era, regarding the role of ncRNAs in the pathogenesis, diagnosis, and potential treatment of neurodevelopmental disorders. Methods: A comprehensive literature search was conducted to identify studies reporting on the expression profiles, functional implications, and clinical relevance of ncRNAs in neurodevelopmental disorders, across both human and animal models. Results: Here, we highlight that multiple classes of ncRNAs are differentially expressed in individuals with ASD and ADHD. Notably, specific miRNAs and lncRNAs demonstrate potential as diagnostic biomarkers with high sensitivity and specificity. Functional studies further reveal that ncRNAs actively contribute to pathogenic mechanisms by modulating neuronal gene networks. Conclusions: Emerging experimental data indicate that the exogenous administration of certain ncRNAs may reverse molecular and behavioral phenotypes, supporting their therapeutic promise. These findings broaden our understanding of neurodevelopmental regulation and open new avenues for personalized diagnostics and targeted interventions in clinical neuropsychiatry. Full article

In this study, we investigated the effects of dietary supplementation with thermally modified attapulgite on the daily weight gain, serum biochemical indices, and serum metabolites of Simmental fattening cattle. A total of 30 healthy Simmental fattening beef calves of similar age (8 to 9 months old) and body weight (370 ± 10 kg) were randomly divided into two groups, each containing 15 animals. A control group was fed the basal diet, and a treatment group was fed the same basal diet with the addition of 4 g/kg of thermally modified attapulgite. After 75 days of formal experiment, the calves in the two groups were weighed, and blood samples were collected by tail vein blood sampling for determinations of the serum biochemical indices and serum metabolites using liquid chromatography–mass spectrometry (LC-MS) analysis. The results indicated that the addition of thermally modified attapulgite to the diet had no significant effects on the daily weight gain of fattening beef cattle. After feeding with modified attapulgite, the glutathione peroxidase and superoxide dismutase activities in the serum of the experimental group were 55.02% (257.26 U·mL⁻¹ to 165.95 U·mL⁻¹, p < 0.05) and 13.11% (18.98 U·mL⁻¹ to 16.78 U·mL⁻¹, p < 0.05) higher than that in the control group. Compared with the control group, the tumor necrosis factor-alpha content was reduced by 14.50% (31.27 pg·mL⁻¹ to 36.57 pg·mL⁻¹, p < 0.01), and the concentration of interleukin-6 and lipopolysaccharide decreased by 17.00% (34.33 pg·mL⁻¹ to 41.36 pg·mL⁻¹, p < 0.001) and 23.05% (51.34 EU·L⁻¹ to 66.72 EU·L⁻¹, p < 0.001) in the serum of the experimental group. Contrastingly, the thermally modified attapulgite had no significant effects on the levels of serum total protein, albumin, or globulin in Simmental fattening cattle (p > 0.05). Furthermore, the results of serum metabolomic analyses revealed that there were a total of 98 differential metabolites, which were mainly enriched with respect to glycerophospholipid metabolism, Th1 and Th2 cell differentiation, autophagy-other, retrograde endogenous cannabinoid signaling, and the NF-κB signaling pathway. Overall, thermally modified attapulgite was found to effectively increase the activity of antioxidant enzymes, reduce serum inflammatory mediators, may suppress oxidative damage, enhance immunity, and have a positive influence on the health of Simmental fattening beef calves. Full article