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The systematic integration of heterogeneous host-pathogen interaction data with disease modules and pharmacological knowledge remains a major challenge in translational biomedical informatics. Network medicine offers a promising strategy for identifying conserved regulatory vulnerabilities and therapeutic repositioning opportunities across distinct mucosal ecosystems. We developed a scalable multilayer network integration framework that unifies pathogen-host protein interactions, disease-risk gene modules, and drug-target associations into a consolidated human interactome. The integrated network comprised 7,262 human proteins, 17,016 high-confidence protein-protein interactions, nine bacterial pathogens, four respiratory viruses, and 514 FDA-approved drugs. Network topology was quantitatively characterized using complementary centrality metrics (degree, betweenness, closeness, clustering coefficient, and topological coefficient) to identify high-influence host regulators. Drug prioritization employed a multi-criteria ranking pipeline integrating functional network scoring (CoDReS), structural similarity clustering (Tanimoto-based hierarchical modeling), and pharmacokinetic constraint filtering (ADMET profiling). Pathway enrichment analysis was performed to identify convergent biological mechanisms. The integrative framework identified conserved cross-ecosystem regulatory hubs, including PPARG, CDC42, JUN, RHOA, and CAV1, which link microbial perturbations to cardiometabolic and inflammatory disease pathways. Centrality-weighted drug prioritization consistently ranked indomethacin, ibuprofen, dexibuprofen, mesalazine, and cannabidiol as high-confidence repositioning candidates for densely connected host networks. Enrichment analyses demonstrated convergence on immune signaling pathways, cytoskeletal remodeling, PPAR signaling, and focal adhesion networks. This study presents a reproducible and generalizable network medicine workflow that formalizes interactome construction, multi-metric centrality assessment, and composite drug ranking in a unified analytical framework. The proposed strategy enables the systematic identification of conserved host regulatory vulnerabilities and repositionable therapeutics across infectious and chronic inflammatory diseases, thereby advancing host-directed therapeutic discovery in translational biomedical informatics.

Spinal cord injury (SCI) disrupts the integrated neuroendocrine network linking the hypothalamic-pituitary-adrenal (HPA) axis, renin-angiotensin-aldosterone system, and sympathetic nervous system, resulting in endocrine and immune dysfunction. However, the effects of SCI on angiotensin II receptor signaling remain unclear. This study investigated temporal and lesion-dependent changes in angiotensin II type 1 (AT1) and type 2 (AT2) receptor expression following SCI in rats. Low-thoracic SCI (Th9 compression, 40 g/15 min) was evaluated over 28 days, while acute responses to partial (Th9) versus near-complete (Th1) sympathoadrenal denervation were compared. Receptor expression was assessed in the hypothalamic paraventricular nucleus, pituitary, adrenal gland, and spleen, and correlated with hormonal and morphological alterations. Surgical stress alone activated systemic angiotensin II signaling. Low-thoracic SCI induced time- and tissue-specific changes in angiotensin receptor expression independent of circulating angiotensin II levels, indicating adaptive remodeling of HPA axis sensitivity. SCI caused transient adrenal enlargement, zona fasciculata hypertrophy, dysregulated HPA axis activity, angiotensin II-independent aldosterone production, and altered catecholamine secretion. Splenic AT1 receptor expression showed early upregulation followed by compensatory downregulation, consistent with dynamic neuroimmune modulation. In contrast, high-thoracic SCI markedly reduced receptor expression across central and peripheral HPA axis components and the spleen, accompanied by decreased corticotropin-releasing hormone, aldosterone, and norepinephrine, stable adrenocorticotropic hormone, and elevated corticosterone and epinephrine. These findings demonstrate that the extent of sympathetic disruption critically determines neuroendocrine-immune responses after SCI and identify sympathetic innervation as a key regulator of angiotensin receptor balance and stress-axis homeostasis following spinal cord trauma.

The most prevalent malignant tumor of the urinary system, bladder cancer, exhibits a rising global incidence rate. However, recent diagnostic and therapeutic techniques, such as ostomy surgery, can effectively prolong patient survival. The majority of patients require support from family carers, presenting considerable challenges to these caregivers. Although existing research has primarily focused on patients' physiological adaptation, quality of life, and the burden on family carers, the moral dilemmas faced by these caregivers have not been explored yet. This study aimed to explore the psychological and moral dilemmas of family caregivers in a specific care situation. Using a descriptive research design, we conducted one-on-one qualitative interviews with 23 patients who had undergone urostomy. The interview time for each patient lasted over 60 min. All the interviewees emphasized that urostomy had significantly influenced their sexual experience. Moreover, we used thematic analysis to analyze the data. All the interviewees emphasized that a urostomy had significantly influenced their sexual experience. Our analysis yielded three primary themes: (1) the tearing of care responsibility and self-life, (2) reconstruction of family roles and relationships, and (3) the contradiction between the best care and practical limitations, and eight subthemes: guilt of giving up, social alienation, sacrifice of physical and mental health, the challenge of intimacy, balance of multiple responsibilities, great economic pressure, limited knowledge and skills, and emotional collapse. This study reveals that family carers of Chinese urostomy patients perceive caregiving as a moral obligation rather than a mere action, viewing self-sacrifice as evidence of virtue within a Confucian ethical framework. Hence, providers must develop culturally sensitive assessment tools, redesign supportive interventions respecting diverse moral perspectives, and establish ethical support systems to bridge understanding between differing moral contexts. This might foster a healthcare system that genuinely honors the carers' moral dignity.

This study aimed to comprehensively assess the implications of long COVID on the health-related quality-of-life (HRQoL) among Japanese adults and to identify its associated factors. This study used prospective cohort data from the CARE Japan Study between January 2022 and January 2023. The outcome of this study was HRQoL, which was measured using SF-12 questionnaire. Self-reported long COVID was the primary independent variable. We fitted adjusted beta regression models to calculate beta regression coefficients with 95% confidence intervals (CI) and average marginal effects (AME) to explore the determinants of HRQoL. We also performed latent class analysis (LCA) to identify unobserved patterns of long COVID symptoms. Final sample size was 1,285. Compared to the participants with no long COVID, the HRQoL among long COVID patients (β: -0.25; 95% CI: -0.36 to -0.14; AME: -0.036) was significantly lower. The effect of long COVID on HRQoL was the most pronounced among the respondents with pre-existing lung diseases (β: -0.72; 95% CI: -1.29 to -0.16; AME: -0.114). LCA identified three subgroups of long COVID patients - class 1, 2, and 3. Compared to the participants with no long COVID, participants belonged to class 1 (β: -0.47; 95% CI: -0.57 to -0.36; AME: -0.065), class 2 (β: -0.48; 95% CI: -0.60 to -0.35; AME: -0.066), and class 3 (β: -0.93; 95% CI: -1.06 to -0.79; AME: -0.148) had poorer HRQoL. Long COVID patients had reduced HRQoL. Female gender, young-age, thin BMI or pre-existing psychological disorders were associated with lower HRQoL. Now, after five years of COVID-19 pandemic about 779 million of COVID-19 cases were reported, as of October 2025. Survivors of COVID − 19 often report complex, multisystemic, persistent or relapsing symptoms for weeks, months, or even years after the initial infection of COVID-19. When the symptoms are persistent or relapsing even after 12 weeks of initial acute infection, it is termed as long COVID. Due to high prevalence, heterogeneous nature, lack of clear diagnostic markers, prolonged, and obscure recovery process, long COVD is posing challenges on individuals’ lives, public healthcare systems, and workforce. Increasing evidence is suggesting that long COVID is impairing functional and cognitive capacity of the patients resulting poor health-related quality-of-life. Longitudinal studies on health-related quality-of-life among COVID-19 survivors with long follow up period is scarce in Japan. Therefore, in our study we measured the impact of COVID-19 infection on the health-related quality-of-life among Japanese adults with follow up period of 1 year. We found that, long COVID patients had lower health-related quality-of-life compared to the COVID-19 survivors without long COVID. The presence of minimal long COVID symptoms lowered the health-related quality-of-life. For COVID-19 cases with lung disease as a comorbid condition, the risk of reduced quality of life remains high even after recovery. Findings of this research will enhance the understanding of the implications of long COVD on individual’s lives and will underscore the need of coordinated approach for long-term treatment, care, and prevention of long COVID through policies, interventions, and integrated health care system.

Supragastric belching (SGB) is a behavioral disorder involving rapid air influx into the esophagus through a transiently relaxed upper esophageal sphincter, followed by immediate expulsion. Unlike gastric belching, it is not related to lower esophageal sphincter (LES) dysfunction or gastroesophageal reflux disease (GERD). Often associated with psychological stress, SGB can significantly impair quality of life and some patients remain refractory to conventional therapies. In this retrospective study, clinical records of patients diagnosed with refractory supragastric belching were systematically analyzed. Extracted data included detailed clinical history and upper gastrointestinal endoscopy findings; high-resolution esophageal manometry (HREM) was performed using Herbert's 16-channel water perfusion system, with interpretation of esophageal motility patterns based on the Chicago Classification version 3.0 and perceived stress levels assessed using the PSS-10 questionnaire. All patients underwent a standardized intervention protocol consisting of nasogastric tube insertion followed by structured diaphragmatic breathing training (Yellapu Technique), aimed at behavioral modulation of belching. Follow-up evaluations included symptom assessment and perceived stress scores over a three-month period to determine therapeutic response. Total 56 patients were analyzed (40 females and 16 males, mean age of 45.6&#x2009;&#xb1;&#x2009;10.0&#xa0;years). Upper gastrointestinal endoscopy and HREM findings were within normal limits in all patients. Endoscopy showed normal mucosal findings. HREM demonstrated normal esophageal motility and sphincter function, with a baseline esophagogastric junction (EGJ) pressure of 33.75&#x2009;&#xb1;&#x2009;6.45&#xa0;mmHg and an integrated relaxation pressure (IRP) of 10.90&#x2009;&#xb1;&#x2009;2.8&#xa0;mmHg, both within physiological limits. Complete resolution of supragastric belching was observed in 55 patients. The paired mean Perceived Stress Scale (PSS) score showed a statistically significant reduction, decreasing from 33&#x2009;&#xb1;&#x2009;3.65 at baseline to 22.92&#x2009;&#xb1;&#x2009;2.34 at one&#xa0;month (p&#x2009;<&#x2009;0.001). No recurrence of symptoms was reported during the follow-up period. In conclusion, the Yellapu Technique appears to offer a practical and innovative therapeutic approach for the management of refractory supragastric belching. By combining mechanical interruption with behavioral modification, it was associated with immediate symptom relief as well as sustained improvement. These findings suggest that this technique may represent a promising adjunct or alternative to existing therapies, warranting further validation through well-designed prospective controlled studies.

Artificial intelligence (AI) technologies such as machine learning (ML), deep learning (DL), predictive analytics and other tools are rapidly changing pediatric health care, using large amounts of health data. AI tools aid in triage, real-time monitoring and risk stratification in acute care settings, towards improving overall outcomes and fewer complications. During newborn resuscitation, AI analyses real-time data, can guide decisions and enhance training. Computer vision systems with AI tools can generate reliable neonatal bilirubin estimates without the need for blood sampling. AI technology is also being used in the management of necrotising enterocolitis, respiratory distress syndrome, and screening and early diagnosis of retinopathy of prematurity. ML models assist in detecting brain injuries on MRI for conditions such as hypoxic-ischemic encephalopathy, intraventricular hemorrhage; MRI biomarkers can be analyzed using AI to predict neurodevelopmental outcomes. AI-based clinical decision support systems have been deployed to enhance workflows and outcomes by early detection of disease, reducing medication errors and help clinicians improve decision-making. However, there remain ethical and practical challenges in the use of AI including data privacy, the need for high-quality pediatric datasets, rigorous clinical validation and transparency, to ensure that AI strengthens clinical judgement and is trustworthy.

Ferroptosis is an iron-dependent form of programmed cell death characterized by lipid peroxidation. Oxidative stress, a pathological state of reactive oxygen species (ROS) imbalance, exerts a complex biphasic regulatory effect on it. This review elucidates that the pro-death or anti-death outcome of oxidative stress is not random but determined by an integrated decision-making framework. This framework encompasses three core dimensions: stress parameters (e.g., ROS intensity, duration, and subcellular source), cellular context (e.g., cell type, differentiation status, and biological sex), and microenvironmental signals (e.g., hypoxia and inflammation). Mechanistically, high-intensity stress promotes ferroptosis by facilitating membrane phospholipid-specific lipid peroxidation via the Fenton reaction, disrupting iron homeostasis, and depleting glutathione to inactivate GPX4. By contrast, moderate stress activates adaptive defense programs via transcription factors such as Nrf2 and FOXO, upregulating GPX4 and HO-1 and reprogramming iron and lipid metabolism to maintain homeostasis. This review is the first to systematically incorporate the FOXO transcription factor family as a key regulatory node and emphasizes that the spatiotemporal specificity of redox signaling is essential for understanding its biphasic output. We utilize newly added summary tables to conduct a comparative analysis of the context-dependent biphasic behaviors of core nodes, disease-specific biomarkers, and defense systems across various pathologies and delineate the difference between universal conserved mechanisms and disease-specific mechanisms. This synthesis advances the discussion from phenomenon to framework, deepening the understanding of pathologies like neurodegenerative diseases, cancer, and ischemia-reperfusion injury and providing a clear conceptual blueprint and translational pathway for the formulation of spatiotemporally precise therapeutic strategies.

Extracellular vesicles (EVs), including exosomes (EXOs) and microvesicles, are small particles surrounded by lipid bilayers that almost all cell types produce. They are essential for cell signaling because they transport bioactive molecules, including DNA, RNA, proteins, and lipids. The amount and make-up of EXOs are linked to several illnesses, including inflammatory diseases, cancer, metabolic diseases, and the one we're communicating about here, female infertility. Bacteria, fungi, viruses, and parasites are just a few of the organisms known to affect the reproductive system in both men and women. EVs are very important for reproductive health, and they can be a cause of infections that make women unable to have children. EVs play a significant role in cell communication and can influence both healthy and pathological processes in the female reproductive system. We looked into the use of EVs as an alternative way to treat vaginal infections (VIs), like bacterial vaginosis, viral vaginitis, and vaginal yeast infections, because traditional treatments for these diseases have some problems. In this study, we also examined the role of EVs in infertility associated with VI. Then, the pros and cons of this method for treating this sickness in the future are discussed.

Patient-reported outcome measures (PROMs), when used at the point-of-care, provide a mechanism to systematically integrate patients' voices into shared decision-making. We examined clinicians' perspectives on the acceptability and preferred timing of PROM completion in routine clinical care for respiratory, musculoskeletal, cardiac, kidney and diabetic condition management. Semi-structured interviews were conducted over videoconference between October 2024 and May 2025. Participants worked at various New South Wales Health clinics, providing care for patients with chronic conditions, and were eligible to collect and review PROMs digitally using the Health Outcomes Patient Experience platform (NSW PRMs-HOPE program). Reflexive thematic analysis was undertaken. Twenty-two physiotherapists and nurses were interviewed. Acceptability themes included: (1) purpose of PROMs; (2) broader ethical considerations for PROMs collection and use; (3) practical aspects of PROM administration. Findings highlighted the elusiveness of an "ideal" timing for PROMs. Timing themes included: (1) (mis)alignment in timing of PROM administration; (2) preferences for fixed or customised timing and frequency of administration; (3) temporal fit and workflow alignment. PROMs were reported as most acceptable when their selection, content, and timing aligned with clinical purpose, scope of practice, and existing workflows. Flexibility in PROM administration was perceived to enhance relevance at the point-of-care and support timely, condition-specific clinical conversations and interventions. However, clinicians also recognised that increased flexibility may reduce the comparability of aggregated PROM data across cohorts, highlighting an inherent acceptability trade-off between meeting individual clinical needs and supporting system-level performance monitoring and benchmarking. People with long&#x2011;term health conditions can fill out health surveys called patient&#x2011;reported outcome measures (PROMs). These health surveys help patients share how they are coping day to day and how their health condition or treatment is affecting their quality of life. PROMs are used more in healthcare now, but we do not know enough about how clinicians feel about using them or when they should be given to patients to improve their care.In this study, we spoke with physiotherapists and nurses who use PROMs. They told us what they think about PROMs and when these should be completed by patients.Physiotherapists and nurses said PROMs can help them better understand their patients, find changes in their patients' health, and support conversations about care. But they also said they needed extra time to help patients fill in PROMs, some of the questions were unclear for patients, there were language and cultural barriers for some patients, and they did not always know how to use the results.Overall, physiotherapists and nurses wanted more choice in which PROMs they use and when patients complete them. They felt this would make PROMs more useful for patient care. But, too much choice could make it harder to compare results across clinics and to see how well services are looking after people.

The presence of estrogenic compounds in aqueous environments has raised significant environmental and public health concerns due to their endocrine-disrupting effects. These compounds, both natural (estrone: E1, 17&#x3b2;-estradiol: E2, and estriol: E3) and synthetic (17&#x3b1;-ethinylestradiol: EE2), are frequently detected in wastewater and surface waters, where conventional treatment processes often fail to remove them successfully. Adsorption has been regarded as a promising, low-cost solution for removing these compounds, especially when coupled with activated carbon made from agro-industrial waste. This is considered an&#xa0;environmentally friendly&#xa0;solution, as it reuses waste materials and adds value to them. This review presents a comprehensive analysis of 28 studies published from 2011 to 2026 on the use of activated carbon for the removal of estrogens. It discusses the properties of estrogens, their environmental impact, and the health risks of long-term exposure. It also explains the physicochemical mechanisms behind estrogen adsorption and highlights the main adsorption and kinetic models used, with a reflective discussion on the results. Although results are promising, most studies only performed their assays under ideal matrices or monocomponent systems. Future research should include multicomponent systems, simulated wastewater matrices, and initial estrogen concentrations closer to those found in nature. Challenges remain in improving adsorbent efficiency, regeneration, and overall sustainability.

Microbial fermentation plays a crucial role in industrial biotechnology, however, conventional and manual optimization methods often encounter challenges related to scalability and precision. Despite notable progress, a significant limitation in the current literature remains. Most studies address artificial intelligence or nanotechnology applications in isolation, which limits their ability to overcome multifaceted bottlenecks in real-time control and sustainable scale-up of fermentation processes. This review examines the transformative impact of convergence in artificial intelligence (AI) and nanotechnology on fermentation processes. AI tools, including neural networks, genetic algorithms and deep reinforcement learning, are employed to predict microbial behaviour, adjust conditions in real time and boost yields. Meanwhile, nanotechnology offers smart and innovative solutions, such as nano-carriers and sensors, for targeted microbial modulation and enzyme activation. The review underscores latest research done on AI-optimized fermentation and nanoparticle-assisted systems, showing their potential in streamlining high-throughput screening and scaling up production. Although fully integrated AI-nanotech fermentation systems are still in development, current research indicates significant potential across sectors like biofuels, food and pharmaceuticals. Synergistically, these innovations suggest a more intelligent and sustainable future for bio-manufacturing, one that aligns with circular bio-economy objectives and advances key United Nations Sustainable Development Goals.

Immunotherapy has emerged as a pivotal approach in cancer treatment, harnessing the body's immune system to recognize and eradicate tumor cells. The search for novel compounds that can enhance immune responses while selectively targeting cancer cells remains a significant area of research. This study investigates the immunotherapeutic and antitumoral potential of fatty acids derived from the subantarctic red macroalgae Sarcopeltis skottsbergii. The cytotoxic effects of these fatty acids were evaluated in vitro using HCC1954 (breast cancer), HL-60 (leukemia), and CHO (non-tumoral) cell lines. Results demonstrated significant inhibition of cell proliferation by MTT assay in HCC1954 and HL-60 cell lines (52% and 57.9% of growth inhibition, respectively), with no observed cytotoxicity in CHO cells. Cytotoxicity was also confirmed by fluorescence assay (LIVE/DEAD). Additionally, real-time PCR analysis conducted on the J774A.1 macrophage cell line and primary culture of mice splenocytes revealed increased expression of interleukins IL-4, IL-6, IL-10, IL-12, IL-17, TNF-&#x3b1;, and IFN-&#x3b3;, which play a pivotal role in the immune system, indicating a balanced immune response that both mitigates excessive inflammation and promotes direct antitumor activity. These findings suggest that fatty acids from S. skottsbergii can adapt an immune response, contributing to the immunomodulation of the tumor. The absence of cytotoxicity in non-tumoral cells, combined with selective inhibition of cancer cell growth and immune activation, highlights the potential of S. skottsbergii fatty acids as a promising adjuvant in cancer therapy. These results underscore the value of natural compounds from marine sources in developing innovative immunotherapeutic strategies against cancer.