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Abstract: Within the framework of the Algerian vision that emphasizes the importance of digital transformation in all sectors, including the health sector, the Algerian Ministry of Health intends to develop an integrated digital health system, through the adoption of the latest digital technologies to contribute to enhancing the efficiency of the sector and achieving its strategic goals. The results showed several suggestions, the most important of which are valuing the efforts exerted and enhancing them with the necessary capabilities, reducing costs and addressing deficiencies, emphasizing the importance of investing in modern digital technologies, and working to develop competencies, to build an integrated and effective health system that contributes to improving the quality of services and meeting the needs of citizens better. Keywords: Algerian strategy; digital transformation; health sector; public utility; e-health.

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En el contexto de crisis y globalización, el Plan Bolonia ha generado un modelo universitario cuya formación se orienta casi exclusivamente hacia el acceso al mercado laboral. Consecuentemente, la subordinación a determinadas temáticas deja fuera asuntos emergentes que no encuentran cabida en los planes de estudio y solo aparecen en proyectos de innovación educativa y proyectos de aprendizaje-servicio que favorecen una relación entre la academia y la realidad. Este artículo presenta la experiencia de aprendizaje-servicio llevada a cabo desde un taller experimental en la Escuela de Arquitectura que abordó la necesidad de introducir la consideración de grupos no humanos en los procesos urbanos. Mediante el análisis de la experiencia a través de un registro sistemático cualitativo y de una revisión teórica, los resultados permiten ser valorados positivamente, detectando en el alumnado un creciente interés por promover un compromiso con lo más que humano desde un enfoque situado.

Treatment of the disorders affecting skull base and craniovertebral junction (С1-С2, C1-C3) associated with craniovertebral instability is an unresolved issue of modern neurosurgery. Patients are often denied surgical care due to the disorder complexity, and treatment is limited to conservative methods (cervical collar, halo apparatus) that are palliative in nature. Patients with craniovertebral pathology have been considered to be radically inoperable until recently. Advanced methods for treatment of patients with various disorders affecting skull base and craniovertebral junction are used and developed in the Burdenko Neurosurgical Center.

The landscape of ophthalmology has observed monumental shifts with the advent of artificial intelligence (AI) technologies. This article is devoted to elaborating on the nuanced application of AI in the diagnostic realm of anterior segment eye diseases, an area ripe with potential yet complex in its imaging characteristics. Historically, AI's entrenchment in ophthalmology was predominantly rooted in the posterior segment. However, the evolution of machine learning paradigms, particularly with the advent of deep learning methodologies, has reframed the focus. When combined with the exponential surge in available electronic image data pertaining to the anterior segment, AI's role in diagnosing corneal, conjunctival, lens, and eyelid pathologies has been solidified and has emerged from the realm of theoretical to practical. In light of this transformative potential, collaborations between the Ophthalmic Imaging and Intelligent Medicine Subcommittee of the China Medical Education Association and the Ophthalmology Committee of the International Translational Medicine Association have been instrumental. These eminent bodies mobilized a consortium of experts to dissect and assimilate advancements from both national and international quarters. Their mandate was not limited to AI's application in anterior segment pathologies like the cornea, conjunctiva, lens, and eyelids, but also ventured into deciphering the existing impediments and envisioning future trajectories. After iterative deliberations, the consensus synthesized herein serves as a touchstone, assisting ophthalmologists in optimally integrating AI into their diagnostic decisions and bolstering clinical research. Through this guideline, we aspire to offer a comprehensive framework, ensuring that clinical decisions are not merely informed but transformed by AI. By building upon existing literature yet maintaining the highest standards of originality, this document stands as a testament to both innovation and academic integrity, in line with the ethos of renowned journals such as Ophthalmology.

With the upsurge of artificial intelligence (AI) technology in the medical field, its application in ophthalmology has become a cutting-edge research field. Notably, machine learning techniques have shown remarkable achievements in diagnosing, intervening, and predicting ophthalmic diseases. To meet the requirements of clinical research and fit the actual progress of clinical diagnosis and treatment of ophthalmic AI, the Ophthalmic Imaging and Intelligent Medicine Branch and the Intelligent Medicine Committee of Chinese Medicine Education Association organized experts to integrate recent evaluation reports of clinical AI research at home and abroad and formed a guideline on clinical research evaluation of AI in ophthalmology after several rounds of discussion and modification. The main content includes the background and method of developing this guideline, an introduction to international guidelines on the clinical research evaluation of AI, and the evaluation methods of clinical ophthalmic AI models. This guideline introduces general evaluation methods of clinical ophthalmic AI research, evaluation methods of clinical ophthalmic AI models, and commonly-used indices and formulae for clinical ophthalmic AI model evaluation in detail, and amply elaborates the evaluation methods of clinical ophthalmic AI trials. This guideline aims to provide guidance and norms for clinical researchers of ophthalmic AI, promote the development of regularization and standardization, and further improve the overall level of clinical ophthalmic AI research evaluations.

En este trabajo busco exponer que la crítica de la modernidad de Walter Benjamin ampara una dimensión natural en tanto material residual y arruinado de la dialéctica sujeto-objeto. Para ello, primero, aludo la crisis racional moderna en función del empobrecimiento de la experiencia y el conocimiento, cuya consecuencia se traduce en la tristeza natural y un desbalance subjetivista. A continuación, exploro el materialismo benjaminiano en función de la configuración mercantil de los objetos en el marco del capitalismo. Finalmente, presento la modalidad dual de la técnica y la cuestión de la historia natural. Así, espero mostrar que el materialismo benjaminiano no se detiene en la exposición de la objetividad arruinada, sino que abre una vía racional en la que la naturaleza derruida constituye una materia inacabada de la objetividad, índice de un conocimiento del porvenir no antropocéntrico y, por eso, fundamento para una experiencia histórica divergente.

Lung cancer is the highest cancer-related mortality rate in the world, and is one of the most common malignancies. The standard treatment for early-stage non-small cell lung cancer (NSCLC) is radical lobectomy, while recent studies have found that sub-lobectomy of pulmonary nodules (≤2 cm) is not inferior to lobectomy and even improve the prognosis of the patients. These important findings will effectively and positively promote the formation of consensus and principles of wedge resection of pulmonary nodules (≤2 cm) in the field of thoracic surgery. The purpose of this study is to present a national expert consensus on wedge resection of pulmonary nodules (≤2 cm) in the field of thoracic surgery. The experts from Editorial Committee of Consensus on Wedge Resection of Lung Nodules (≤2 cm) (2023 Edition) jointly participated in the revision work. According to the clinical progress about the wedge resection of pulmonary nodules (≤2 cm) at home and abroad during recent years, experts jointly wrote Wedge Resection of Pulmonary Nodules (≤2 cm): a Consensus Statement by Specialists of Thoracic Surgery (2023 Edition), in combination with the homogeneous treatment principles of wedge resection in the field of thoracic surgery in China. This consensus was summarized from the following aspects: (1) Indications of wedge resection of pulmonary nodules (≤2 cm); (2) Resection range of pulmonary nodules (≤2 cm) required for wedge resection; (3) Excisable pulmonary nodules (≤2 cm) for wedge resection. This consensus finally put forward 8 recommended opinions, and sorted out 5 opinions which were still controversial and needed more evidence. The integrated opinions were generated through the discussion held among the experts of thoracic surgery from all over the country, making wedge resection of pulmonary nodules (≤2 cm) more appropriate for China and more standardized and homogeneous for clinical practice. In the future, more relevant researches should be accumulated based on the characteristics of lung cancer and its diagnosis and treatment in China, optimizing the treatment of pulmonary nodules (≤2 cm).

The joint workshop between U.S. and Japanese researchers, supported by The U.S.–Japan Brain Research Cooperative Program, convened in January 2023 at Keio University Mita campus in Tokyo, Japan. The workshop had a threefold objective. Firstly, it aimed to facilitate robust exchanges between U.S. and Japanese researchers engaged in Neurovascular Unit (NVU) research, enhancing the global network of scholars in the field. Secondly, it aimed to encourage the initiation of collaborative research projects, fostering interdisciplinary efforts and synergistic advancements in understanding the brain vascular physiology and central nervous system. Lastly, the workshop emphasized the nurturing of young researchers, recognizing their pivotal role in shaping the future of NVU research. Throughout the workshop, participants discussed fundamental aspects of the NVU, exploring its complex connections and vital functions. By sharing their expertise and insights, the workshop attendees sought to uncover novel approaches to mitigate the burden of neurological diseases for individuals worldwide. This report provides a summary of the presentations and discussions held during the workshop, showcasing the collective efforts and progress made by the participants. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a common microvascular complication of diabetes necessitating early intervention to impede progression, despite current clinical treatments focusing on advanced stages. Essential oils from Fructus Alpiniae zerumbet (EOFAZ) have demonstrated efficacy in protecting against high glucose (HG)-induced Müller cell activation and DR development. This study introduced a reactive oxidative species (ROS)-responsive drug delivery system (NPS PHE @EOFAZ) targeting early DR stages and oxidative stress. Our engineered nanoparticles effectively deliver EOFAZ into HG-exposed Müller cells by detecting and responding to elevated oxidative stress levels. The NPS PHE @EOFAZ significantly inhibited abnormal cell growth, reduced oxidative stress, and alleviated inflammation in vitro. In vivo experiments on diabetic mice with DR revealed that NPS PHE @EOFAZ mitigated early pathological changes by reducing oxidative stress and inflammation while also alleviating organ damage in the heart, liver, spleen, lung, and kidney. These findings underscore the potential of NPS PHE @EOFAZ as a promising antioxidant for early intervention in DR pathogenesis.

Objective: To evaluate the experiences of caregivers (patients' companions and nurses) in managing pressure injuries (PIs) in patients in palliative care., Methods: Included in this qualitative phenomenologic study were 10 caregivers (five patient companions and five nurses) involved in the care of five patients hospitalized in the palliative care unit of a single facility between January and March 2023. The research data were collected through face-to-face, in-depth interviews using semistructured interviews., Results: Two main themes emerged from the interviews: "approach to care" and "factors affecting the care of PIs." Regarding "approach to care," subsidiary analytic themes included "management of PIs" and "feelings." For "factors affecting the care of PIs," analytic themes were "level of knowledge," "facilitators," "difficulty in caregiving," and "experience of care.", Conclusions: The interviewed nurses and patients' companions identified factors facilitating and complicating the effective management of PIs, knowledge of which may steer the development of strategies by healthcare providers and administrators that meet the needs of healthcare personnel. These findings may contribute to creating interventions and policies for managing PIs, potentially increasing the patients' quality of life., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To investigate the impact of darker skin tones on skin tolerance to shear forces in the context of pressure injuries (PIs) and explore the mechanobiological hypothesis that people with darker skin may be at an increased PI risk due to altered biomechanical skin properties resulting from a lower water content (WC) as some literature suggests., Methods: The authors developed a computational modeling framework simulating skin with varying Poisson ratios to represent different WC levels in the stratum corneum (SC), focusing on the effects of ethnicity and WC on mechanical stresses in superficial skin during weightbearing postures. Mechanical properties of the tissues were based on literature values. Pure compression and compression with shear were applied to the skin model., Results: A lower Poisson ratio in the SC, indicating lower WC, is associated with higher tissue stresses and more intense stress concentrations, especially under combined compression and shear loading. The initial reduction in the Poisson ratio had the most significant impact on increased tissue loading. These results support the hypothesis that the lower WC in darker skin, associated with increased transepidermal water loss, may lead to altered biomechanical behavior and increased PI risk., Conclusions: The modeling suggests that reduced WC and increased transepidermal water loss, notably present in darker skin tones, lead to higher stress concentrations within the SC, thus elevating the PI risk. Comprehensive clinical and biomechanical data across various skin tones are needed to improve the practice of PI prevention in individuals with darker skin., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although most pressure injuries (PIs) are healable with appropriate assessment, preventive intervention, and treatment, nursing professionals recognize that some PIs are unavoidable. Research investigating unavoidable PIs is limited because there are few clear means of determining whether these injuries are unavoidable., Objective: To clarify the reality of unavoidable PIs by analyzing the state of PIs and blood test results in patients who were actively dying., Methods: From 2018 to 2023, 904 hospitalized patients at the author's medical center developed PIs. Of these patients, 710 survived and were discharged (survival group). Of the 194 patients who died after developing a PI, 111 died more than 8 days after onset (end-of-life group), and 83 patients died within 7 days of onset (actively dying group). The researcher analyzed patients' age, weight, and height, as well as various blood work parameters at the time of PI occurrence in the survival, end-of-life, and actively dying patient groups., Results: Approximately half of patients with PIs in the actively dying stage had cancer. Total protein, albumin, and blood urea nitrogen were significantly lower among the actively dying patients compared with those who survived. Aspartate transferase, alanine aminotransferase, white blood cell count, and C-reactive protein were all significantly higher among patients in the actively dying versus the surviving group., Conclusions: It is difficult to determine whether a PI is unavoidable. However, the author believes that clinical symptoms and blood test data can help make that decision., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Altered localized microclimate conditions are known to increase the risk of pressure injuries in immobile patients. Limited in vivo studies have examined how skin properties change over time and under different skin microclimate conditions., Objective: To examine changes in erythema, stratum corneum hydration, and skin temperature in response to an altered microclimate, simulated by the introduction of heat, at the skin-support surface interface of semirecumbent healthy adults., Methods: In this quasi-experimental study, researchers obtained noninvasive biophysical skin measures at the elbows, heels, and sacrum of healthy adults positioned semirecumbently. Participants advanced through a controlled condition and heat intervention. Repeated measures were gathered at the anatomic sites every 10 minutes for 60 minutes per condition. Linear mixed models were used to compare skin measures over time and between conditions., Results: Large regional variation in skin measures emerged by condition and among participants. The introduction of heat increased skin temperature at the heels (P < .001), elbows (P = .005), and sacrum (P < .001). Erythema increased at the sacrum (P = .012) but at no other anatomic testing site. There was no impact on stratum corneum hydration as a result of increased heat at any anatomic testing site., Conclusions: More frequent monitoring cycles for erythematous skin discoloration and thermal changes may be required at the sacral skin in immobile patients. Distinctive protocols in relation to skin-care regimens may be warranted for individual patients. Skin cooling, enabled by intermittent off-loading of pressure-prone areas, may assist optimization of the skin microclimate., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To identify markers associated with pressure injury (PrI) history in individuals with spinal cord injury (SCI) using two approaches: skin blood flow (SBF) response toward localized heating, and serum marker for insulin resistance., Methods: For this cross-sectional, observational study of adults with chronic traumatic SCI at T12 and above, researchers recruited two groups of participants: with history of PrI (group 1), and without history of PrI (group 2). The study protocol included obtaining fasting blood samples and measurement of SBF at bilateral heels with localized heating of 42 °C for 30 minutes from all participants. Primary SBF outcomes were initial peak and plateau SBF normalized to baseline SBF. The primary outcome for insulin resistance was Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), calculated from fasting plasma glucose and insulin. Secondary outcomes included demographic and SCI information. Researchers used the Fisher exact test and Wilcoxon-Mann-Whitney test to compare the intergroup difference of categorical and continuous variables, respectively., Results: Sixteen adults completed this study (group 1, n = 7; group 2, n = 9). In comparison with group 2, group 1 had significantly higher HOMA-IR (3.90 ± 0.71 vs 1.45 ± 0.71), suggesting higher insulin resistance, and longer duration of injury (22.54 ± 7.24 vs 7.98 ± 6.58 years). There were no between-group differences in SBF or other secondary outcomes., Conclusions: HOMA-IR is a novel serum index associated with PrI history in persons with chronic SCI. Future longitudinal study is warranted to examine the role of insulin resistance in increasing PrI risk for the SCI population., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

The standardisation of ethograms offers behavioural researchers many practical advantages. They make it possible to describe behavioural repertoires and their occurrence in different contexts accurately. As there is no standardised ethogram for Psittaciformes in the scientific literature, this study aimed to create one by compiling information from scientific articles to facilitate and standardise the naming and description of the group's behaviours, allowing for future comparisons between studies. Bibliographic searches for ethograms were carried out on the Scopus and Web of Science platforms, and the selected papers were evaluated to identify the terminology used for the behaviours and their description. The standardised ethogram for Psittaciformes was finalised with 102 behaviours, divided into 11 behavioural categories. The category with the highest number of behaviours was activity. Only 21 species of the order were covered, most from the Psittacidae family, representing 5 % of the 421 described species. Of the articles containing ethograms, 76 % of the authors created them rather than using those already published in the scientific literature. These results collectively indicate the importance of having a standardised ethogram for the Order, as this would facilitate future studies for the group. The standardised ethogram was built in the present study to facilitate behavioural researchers with more precise definitions of all the behaviours and to help unify and compare behavioural research on Psittaciformes., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: Few studies have investigated the application of massage to bony prominences, and international guidelines do not currently recommend additional massage in these areas., Objective: To investigate the impact of the effleurage technique, a component of classical massage known for its clinical applicability and practicality, in preventing pressure injuries (PIs)., Methods: The study focused on bedridden patients in the ICU of a state hospital. The sample included patients admitted between July 1, 2021, and November 30, 2021, without preexisting PIs. Using a randomized controlled trial design with simple randomization, routine nursing care was provided to the control group of 30 patients, and the experimental group of 30 patients received classical massage (effleurage technique) in addition to routine care. Both groups were followed up for an average of 12 days using various assessment tools, including a patient information form, the Braden Risk Assessment Scale, the Pressure Wound Staging Form, and an experimental/control group follow-up form., Results: The research results revealed a statistically significant impact of massage application on preventing PIs (P < .05). The average day of PI development was 10.93 ± 2.31 in the experimental group and 6.79 ± 4.42 in the control group., Conclusions: The study findings suggest that the effleurage technique, as part of classical massage, can be integrated into nursing practices to effectively prevent PIs., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Advances in knowledge about late effects of childhood cancer treatments have led to implement long-term follow-up care. This raises the question of the ethical issues involved in providing information to survivors, and in proposals for long-term follow-up consultations., Method: We conducted a two-part qualitative study: (1) A semi-directive interview survey to explore survivors' experiences of medical proposals for follow-up consultations; (2) The creation of a multidisciplinary ethical reflection group aimed at identifying the ethical issues associated with the systematization of follow-up care., Results: The study identified five key issues related to medical requests and the implementation of follow-up care: (1) The needs and expectations of former patients regarding information; (2) The temporality of after-cancer; (3) The ambivalence of categorizations in light of the diversity of post-cancer experiences; (4) The role of various professionals and the responsibility for follow-up; (5) The plurality of needs and proposed approaches., Discussion: In light of these issues, five areas of concern emerge: (1) Provide information about a risk in life after the disease? (2) When should follow-up be proposed? (3) The category of "former patients": relevant or problematic? (4) Who can or should assume the role and responsibility for follow-up? (5) The diversity of follow-up approaches: balancing standardization with reliance on informal networks., (Copyright © 2025 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Due to the anti-inflammatory and antioxidant properties of cynaroside (Cyn), it may be useful in the treatment of cerebral ischemia/reperfusion injury (I/R). This study aims to evaluate the effect of Cyn on cerebral ischemia/reperfusion injury., Methods: Transient middle cerebral artery occlusion model (tMCAO) and oxygen and glucose deprivation/reperfusion (OGD/R) microglia models were used to evaluate the effect of Cyn. The direct interaction between Cyn and Alox15 was investigated through bioinformatics, molecular docking and biolayer interferometry., Results: tMCAO mice treated with Cyn show improved neurological deficits, reduced infarct volume and edema, and inhibition of microglial activation. In addition, Cyn inhibited tMCAO-induced Alox15 expression. Cyn significantly reduced the overproduction of the M1 microglia-regulated pro-inflammatory cytokines NLRP3, ASC, and cleaved caspase-1, as well as the overproduction of IL-1β and IL-18, induced by tMCAO or OGD/R. Cyn also inhibits the expression of Tfrc, COX2, and Acsl4 in tMCAO and OGD/R-treated mice and BV-2 cells., Discussion: These results suggest that Cyn may attenuate cerebral ischemia/reperfusion injury by inhibiting Alox15 to reduce inflammation and reduce ferroptosis. This study reveals the underlying molecular mechanism of Cyn in the treatment of ischemic stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Cao, Hu, Yu, Long, Sun, Lei, Xie and Yu.)

Obesity is a complex and growing global concern, affecting one in eight individuals and compromising health, quality of life and life expectancy. It carries significant metabolic, cardiovascular, oncological, hepatorenal, skeletal and psychiatric risks, imposing substantial costs on health-care systems. Traditional treatments have often been ineffective or have led to relapse after lifestyle changes. Whereas bariatric surgery is effective, it also involves risks such as mortality and hospitalisation. Semaglutide, licensed in 2018, is a synthetic analogue of glucagon-like peptide 1 which regulates glucose metabolism and gastrointestinal (GI) motility. Studies show that semaglutide, administered either weekly and subcutaneously, or daily orally, induces an average weight loss of -11.62 kg compared to placebo and reduces waist circumference by up to -9.4 cm. It also improves blood pressure, fasting glucose levels, C-reactive protein levels and lipid profiles. The most common adverse events are mild-to-moderate GI complaints occurring more frequently with daily administration than weekly doses; hypoglycaemia is more common without lifestyle intervention. Weight regain often follows semaglutide withdrawal. Furthermore, semaglutide offers cardiovascular benefits for patients with established atherosclerotic cardiovascular disease (CVD), lowers the risk of kidney outcomes and cardiovascular-related death, resolves nonalcoholic steatohepatitis in many cases, and positively impacts mental health and quality of life. In conclusion, semaglutide therapy could significantly benefit many adults regarding CVD and mortality if made widely accessible. Ethical and financial considerations must be addressed for personalised obesity treatment approaches., (© 2025 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: The incidence of hepatocellular carcinoma (HCC) is on the rise worldwide, due to the increasing prevalence of liver diseases associated with metabolic dysfunction and better management of cirrhosis and its complications. The diversification of HCC treatments has recently increased, with the choice of strategy based on HCC characteristics, liver function and comorbidities. The combination of new therapies has transformed the prognosis, with up to 70% survival at 5 years., Objective: The aim of this review was to analyse the most recent data on preoperative evaluation, peri-operative anaesthetic management of liver resection, liver transplantation and other types of procedures, and to highlight the multidisciplinary aspect of such management., Main Findings and Discussion: The importance of preanaesthetic evaluation will depend largely on the procedure proposed, associated co-morbidities and the stage of liver disease. This assessment should verify stabilisation of all comorbidities, and evaluate the degree of portal hypertension, cirrhosis severity and sarcopenia. Liver resection and liver transplantation for HCC present specific surgical challenges, and minimally invasive techniques improve recovery. Nonsurgical procedures considered as therapeutic (ablation) or standby (regional embolisation) are diverse, and all expose patients to specific intra-anaesthetic complications, sometimes requiring intensive care management. Peri-operative anaesthetic strategies deployed in the management of liver resection or nonsurgical procedures involve specific management of fluids, coagulation, narcosis and analgesia, which can impact on patients' overall, and cancer prognosis. Lastly, new down-staging strategies combining several types of procedure and possibly immunotherapy, also call for collegial reflection on posthepatic transplant immunosuppression, which must remain tailored to each individual patient., (Copyright © 2025 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Incidence of osteoarthritis (OA) was increased in patients with asthma, while no prospective cohort study has tested the association of asthma with OA, and the modified effect of social isolation and loneliness remains unclear., Methods: This prospective cohort study included 448,920 participants without OA at baseline from UK Biobank cohort. The evaluation of asthma was based on diagnosis and self-reported history. The outcome was OA including knee OA, hip OA and hand OA by referring to hospital admission records. Two Cox regression models were constructed to assess the relationship of asthma and risk of OA., Results: With a median of 12.5 years of follow up, a total of 57,573 incident OA were recorded. Compared with participants without asthma, the hazard ratios (HRs) were 1.32 (95% CI: 1.29-1.35) for all OA, 1.21 (95% CI: 1.16-1.25) for knee OA, 1.12 (95% CI: 1.07-1.18) for hip OA and 1.62 (95% CI:1.42-1.85) for hand OA in participants with asthma. In addition, we found that social isolation and loneliness significantly modified the associations of asthma with OA (P-interaction < 0.001). Asthma was a stronger predictor of OA than lifestyle risk factors including smoking, alcohol and healthy diet., Conclusions: In this cohort study of UK Biobank participants, asthma was related to increased risk of OA; such association was more pronounced among those with higher social isolation or loneliness score., Competing Interests: Declarations. Ethics and consent to participate: This research was conducted under the UK Biobank application 80610. The UK Biobank study was approved by the National Health and Social Care Information Management Board and the North West Multicentre Research Ethics Committee (11/NW/0382). Consent for publication: All studies included in this study got informed consent from each study participant and each study was approved by the ethics committee or institutional review board. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

There is growing evidence that a wide range of human diseases and physiological traits are influenced by genetic variation of cis-regulatory elements. We and others have shown that a subset of promoter elements, termed Epromoters, also function as enhancer regulators of distal genes. This opens a paradigm in the study of regulatory variants, as single nucleotide polymorphisms (SNPs) within Epromoters might influence the expression of several (distal) genes at the same time, which could disentangle the identification of disease-associated genes. Here, we built a comprehensive resource of human Epromoters using newly generated and publicly available high-throughput reporter assays. We showed that Epromoters display intrinsic and epigenetic features that distinguish them from typical promoters. By integrating Genome-Wide Association Studies (GWAS), expression Quantitative Trait Loci (eQTLs) and 3D chromatin interactions, we found that regulatory variants at Epromoters are concurrently associated with more disease and physiological traits, as compared with typical promoters. To dissect the regulatory impact of Epromoter variants, we evaluated their impact on regulatory activity by analyzing allelic-specific high-throughput reporter assays and provided reliable examples of pleiotropic Epromoters. In summary, our study represents a comprehensive resource of regulatory variants supporting the pleiotropic role of Epromoters., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The impact of four clinically significant genetic variants of endothelial nitric oxide synthase (eNOS) polymorphisms on the concentrations of nitric oxide [NO] and peroxynitrite [ONOO - ] has been given scant consideration. This study utilized a [NO]/[ONOO - ] ratio to determine the extent of endothelial dysfunction caused by these variations in the eNOS gene. The single nucleotide polymorphisms (T-786C, C-665T, and Glu298Asp) and a variable number of tandem repeats (intron 4 a/b/c) were genotyped in human umbilical vein endothelial cells (HUVEC), using sanger sequencing and DNA electrophoresis, respectively. Nanosensors were used to determine the maximal [NO] and [ONOO - ], while traditional and low-temperature SDS-PAGE were used to evaluate the expression of eNOS and the eNOS dimer-to-monomer ratio, respectively. The study results indicate that the eNOS haplotype H3 (G T/C C 4a/c allele) may have a protective effect against cardiovascular disease (CVD) with the [NO]/[ONOO - ] ratio higher than 2. However, the eNOS haplotypes H2 (G T/C C 4a/b) and H5 (T T/C C 4b) increase the susceptibility to CVD with [NO]/[ONOO - ] ratio lower than 1. The results suggest that certain eNOS genetic variants may influence susceptibility to cardiovascular disease (CVD) while other variants may have a protective effect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

GATA2 germline mutations lead to a syndrome characterized by immunodeficiency, vascular disorders and myeloid malignancies. To elucidate how these mutations affect hematopoietic homeostasis, we created a knock-in mouse model expressing the recurrent Gata2 R396Q missense mutation. Employing molecular and functional approaches, we investigated the mutation's impact on hematopoiesis, revealing significant alterations in the hematopoietic stem and progenitor (HSPC) compartment in young age. These include increased LT-HSC numbers, reduced self-renewal potential, and impaired response to acute inflammatory stimuli. The mature HSPC compartment was primarily affected at the CMP sub-population level. In the mutant LT-HSC population, we identified an aberrant subpopulation strongly expressing CD150, resembling aging, but occurring prematurely. This population showed hyporesponsiveness, accumulated over time, and exhibited allele-specific expression (ASE) favoring the mutated Gata2 allele, also observed in GATA2 mutated patients. Our findings reveal the detrimental impact of a Gata2 recurrent missense mutation on the HSC compartment contributing to its functional decline. Defects in the CMP mature compartment, along with the inflammatory molecular signature, explain the loss of heterogeneity in HPC compartment observed in patients. Finally, our study provides a valuable model that recapitulates the ASE-related pathology observed in GATA2 deficiency, shedding light on the mechanisms contributing to the disease's natural progression., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The current research focused on the synthesis of two series of pyrazole derivatives and evaluation of their insecticidal effectiveness. In the first series, seven pyrazole Schiff bases 3a-g were successfully synthesized with yields (79-95%) by condensing phenylfuran-2-carbaldehyde with substituted pyrazole rings. In the second series, eleven amino acid-pyrazole conjugates 6a-k were synthesized utilizing acetic acid, sulfuric acid, morpholine, and EDC. HCl achieving yields of 59% to 94%. The synthesized compounds were assessed for their chemotherapeutic efficacy against locusts and termites by calculating LC 50 values, thereby determining their potential as anti-termite and anti-locust agents. Among the eighteen synthesized pyrazole compounds, the Schiff base pyrazole molecules 3f (LC 50  = 0.001 μg/mL) and 3d (LC 50  = 0.006 μg/mL) demonstrated excellent anti-termite activity compared to the reference drug fipronil (LC 50  = 0.038 μg/mL). Pyrazole derivative 6 h with LC 50  = 47.68 μg/mL exhibited superior anti-locust activity than the reference drug fipronil (LC 50  = 63.09 μg/mL). Additionally, compound 3b, containing NO 2 functionality at the meta position, exhibited notable and significant anti-locust activity with an LC 50 values of 100.00 μg/mL. However, the highest mortality was caused by the glycine conjugate of fipronil 6 h of the 2nd series with an LC 50 value of 47.68 μg/mL, which also proved to be a potent anti-locust agent. This study explores the efficacy of biologically active pyrazole structures as potential insecticidal agents through a combination of virtual molecular docking analysis and biological experimental investigations. The results demonstrate a strong correlation between the computational predictions and experimental outcomes, suggesting that the pyrazole derivatives exhibit significant insecticidal properties. The findings highlight the potential of these compounds in the development of innovative insecticides, paving the way for future research in pest control strategies., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s).)

Oncostatin M (OSM) is a cytokine with the unique ability to interact with both the OSM receptor (OSMR) and the leukemia inhibitory factor receptor (LIFR). On the other hand, OSMR interacts with IL31RA to form the interleukin-31 receptor. This intricate network of cytokines and receptors makes it difficult to understand the specific function of OSM. While monoallelic loss-of-function (LoF) mutations in OSMR underlie autosomal dominant familial primary localized cutaneous amyloidosis, the in vivo consequences of human OSM deficiency have never been reported so far. Here, we identified three young individuals from a consanguineous family presenting with inherited severe bone marrow failure syndromes (IBMFS) characterized by profound anemia, thrombocytopenia, and neutropenia. Genetic analysis revealed a homozygous one base-pair insertion in the sequence of OSM associated with the disease. Structural and functional analyses showed that this variant causes a frameshift that replaces the C-terminal portion of OSM, which contains the FxxK motif that interacts with both OSMR and LIFR, with a neopeptide. The lack of detection and signaling of the mutant OSM suggests a LoF mutation. Analysis of zebrafish models further supported the role of the OSM/OSMR signaling in erythroid progenitor proliferation and neutrophil differentiation. Our study provides the previously uncharacterized and unexpectedly limited in vivo consequence of OSM deficiency in humans.

Acute kidney injury (AKI) is defined by the release of pro-inflammatory factors, leading to structural damage in renal tubules and subsequent tubular cell injury and death. Delivering drugs specifically to renal tubules to mitigate tubular cell damage holds potential for AKI treatment. In this work, we developed functional liposomes (LZM-PLNPs-TP) designed to bypass the glomerular filtration barrier and target tubules by leveraging the unique structural and pathological characteristics of glomeruli and tubules. LZM-PLNPs-TP, incorporating lysozyme (LZM) and cationic liposome, and carrying the anti-inflammatory and antioxidant drug Triptolide (TP), demonstrated favorable stability, efficient drug release, and good cytocompatibility in wide TP concentrations (0-100 ng/mL). These liposomes exhibited the enhanced renal accumulation, tubular retention, and cellular targeting through endocytosis by peritubular capillary endothelial cells. The administration of LZM-PLNPs-TP at a minimal TP dosage (0.01 mg/kg) demonstrated significant protection through the mitigation of oxidative stress and inflammation in ischemia/reperfusion injury (IRI) mice, while the naked TP (0.01 mg/kg) exhibited lower efficacy. Following treatment with LZM-PLNPs-TP, levels of serum creatine, blood urea nitrogen, superoxide dismutase, malondialdehyde, as well as the inflammatory cytokines IL-1β and IL-6 in renal IRI mice were found to be significantly reduced by factors of 2.9, 1.7, 0.7, 1.3, 2.1, and 1.9, respectively, compared to mice treated with TP alone. In summary, this study presents an LZM-targeted drug delivery system that synergistically enhances tubular reabsorption and cellular uptake, offering a promising strategy for AKI treatment. STATEMENT OF SIGNIFICANCE: We have designed specialized liposomes (LZM-PLNPs-TP) with targeting capabilities towards renal tubules to enhance cellular internalization, offering a promising therapeutic strategy for AKI treatment. Our research confirms that the increased accumulation of LZM-PLNPs-TP in renal tubules is facilitated by peritubular capillary endothelial cells rather than glomerular filtration. LZM-PLNPs-TP demonstrated effective mitigation of oxidative stress, inflammation suppression, and significant improvement in kidney injury, ultimately leading to the restoration of renal function in murine models of AKI induced by ischemia/reperfusion. This study introduces LZM-targeted liposomes that enhance tubular reabsorption and cellular uptake synergistically, providing a promising therapeutic approach for AKI management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Inc. All rights reserved.)

Liver fibrosis and biological sex variably modulate the risks of hepatocellular carcinoma (HCC) and extrahepatic cancers (EHCs) arising in the context of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we highlight how these variables may have implications in the setting of chemoprevention and precision medicine approaches in MASLD and guide additional research., Competing Interests: Declaration of interests The authors have no interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The global burden of metabolic diseases is increasing, but estimates of their impact on primary liver cancer are uncertain. We aimed to assess the global burden of primary liver cancer attributable to metabolic risk factors, including high body mass index (BMI) and high fasting plasma glucose (FPG) levels, between 1990 and 2021., Methods: The total number and age-standardized rates of deaths and disability-adjusted life years (DALYs) from primary liver cancer attributable to each metabolic risk factor were extracted from the Global Burden of Disease Study 1990-2021. The metabolic burden trends of liver cancer across regions and countries by sociodemographic index (SDI) and sex were estimated. The annual percentage changes in age-standardized DALYs rate were also calculated., Results: Globally, in 2021, primary liver cancer attributable to high BMI and/or high FPG was estimated to have caused 59,970 deaths (95% uncertainty interval [UI] 20,567-104,103) and 1,540,437 DALYs (95% UI 540,922-2,677,135). The age-standardized rates of death and DALYs were 0.70 (95% UI 0.24-1.21) and 17.64 (95% UI 6.19-30.65) per 100,000 person-years. A consistent global rise in liver cancer attributable to metabolic risks was observed from 1990 to 2021, with high BMI identified as the major contributing risk factor. The highest burden of deaths and DALYs of liver cancer consistently occurred in high SDI countries, while the fastest growth trends were observed in low-middle SDI countries. The burdens of high levels of BMI and FPG were higher in men than in women., Discussion: Primary liver cancer attributable to high BMI and/or high FPG imposes an increasingly substantial clinical burden on global public health, particularly in high SDI countries. Rapid growth trends are also found in middle SDI countries., (Copyright © 2025 by The American College of Gastroenterology.)