Search Results (45,488)

Background/Objectives: Milk consumption is inversely associated with stroke risk. However, the average dairy consumption in Japan is below recommended guidelines. Therefore, we aimed to evaluate potential health and economic impacts of increased milk intake to achieve the recommended daily dairy intake for stroke prevention. Methods: A Markov model stratified by sex and age group simulated the effects of achieving the recommended dairy intake—by increasing milk consumption to 180 g/day—on stroke incidence, stroke-related deaths, and national healthcare expenditures among Japanese adults aged 30–79 years over 10 years. Two scenarios were defined; an immediate increase (Scenario 1) and a constant annual growth rate (Scenario 2) in milk intake, whereas the average dairy product consumption in 2023 was maintained in the base-case scenario. Results: Compared with the base-case scenario, increasing milk consumption to 180 g/day was projected to reduce stroke incidence and stroke-related deaths by 7.0% in Scenario 1 and by 3.2% in Scenario 2. National healthcare expenditures for stroke were decreased by 5.1% in Scenario 1 and 2.2% in Scenario 2. Conclusions: Achieving the recommended dairy intake may contribute to reductions in healthcare costs by preventing stroke in Japan. Full article

Background/Objectives: Preterm infants with respiratory distress syndrome (RDS) require mechanical ventilation but risk lung injury This study compared neurally adjusted ventilatory assist (NAVA) with conventional modes regarding respiratory mechanics and clinical outcomes. Methods: We analyzed data from 79 preterm infants born at <32 weeks gestation who were invasively ventilated for RDS and classified into three groups: NAVA (n = 26), volume-targeted (VT; n = 29), and pressure-controlled (PC; n = 24). Respiratory parameters for 6 h post-surfactant administration and clinical outcomes were evaluated. Results: Baseline characteristics were similar across groups. The NAVA group demonstrated the most rapid reduction in peak inspiratory pressure over 6 h (F = 4.125, p = 0.023) and the fastest increase in dynamic compliance during the first 4 h (F = 3.273, p = 0.048). Respiratory rates were significantly lower with NAVA than with VT or PC modes, while tidal volumes were significantly higher in PC than in NAVA or VT modes. Invasive mechanical ventilation duration was shorter in NAVA (3.0 [0.9–4.9] days) than in PC modes (15.1 [0.3–38.5] days, p = 0.031), whereas not significantly different from that in VT modes (3.8 [0.9–13.4] days). While bronchopulmonary dysplasia or death was lower in NAVA (19.2%) than in PC modes (41.7%), the difference was not statistically significant (p = 0.092). Conclusions: NAVA resulted in the fastest reduction in ventilator-delivered pressure and earlier improvement in dynamic compliance while maintaining respiratory rates within physiological ranges and was associated with shorter ventilation duration than PC modes. However, VT modes achieved comparable respiratory parameters and ventilation durations to those achieved using NAVA. Full article

Near-death experiences (NDEs) are profound psychological events known to catalyze significant spiritual transformation, though most research has been conducted in Western contexts. This study investigated perceived changes in spirituality or religiosity following NDEs among adults residing in Jakarta, Indonesia (N = 402 NDErs; 70% female; M_age = 23, SD = 7.93). This population is crucial as spirituality or religiosity are deeply intertwined yet understudied here. Gender differences were non-significant in both continuous (t(400) = 0.43, p = 0.671) and categorical analyses (χ²(2) = 1.03, p = 0.597). Crucially, age emerged as a significant moderator. Early adulthood showed the highest rate of post-NDE increase, significantly exceeding adolescence (z = −2.86, p = 0.004). Conversely, middle adulthood showed higher baseline levels but greater post-NDE stability. Furthermore, pre-existing spirituality or religiosity significantly predicted post-NDE changes (r = 0.174, p < 0.001). Interestingly, non-religious individuals were paradoxically overrepresented among those reporting a decrease (χ²(4) = 15.10, p = 0.004). These findings indicate that age and pre-existing levels of spirituality or religiosity potentially moderate the relationship between NDEs and changes in spiritual or religious levels following NDEs, highlighting the role of developmental and cognitive factors in transformative experiences. This study suggests that NDEs are associated with increased spirituality or religiosity among Indonesians, consistent with the broader global literature on their transformative aftereffects. Full article

Constitutively active KRAS mutations are highly prevalent in lung cancers, but the direct role of its downstream phosphatidylinositol 3-kinase (PI3K) pathway in tumor progression remains unclear. A previous study established the requirement for PIK3CA, the alpha catalytic isoform, in lung tumor development in mouse models with an intact Trp53 tumor suppressor. In this study, we further investigated the requirement of PIK3CA for tumor growth both in vitro and in vivo. We first generated a “KPA” cell line by genetically deleting Pik3ca from a murine lung adenocarcinoma “KP” cell line harboring oncogenic Kras^G12D and lacking Trp53. We also examined the requirement for STK11, a tumor suppressor and metabolic regulator frequently co-mutated with KRAS in lung cancer. We found that Pik3ca is not required for cell survival and growth in vitro, even under anchorage-independent conditions, but reduced the growth rate by 15%. We next orthotopically implanted KP and KPA cells into syngeneic mice and found that PIK3CA is absolutely required for tumor progression, even in the absence of Trp53. Implantation of KP cells, or a “KPS” cell line lacking the Stk11 gene, led to rapid tumor growth and death of all host animals. In contrast, mice implanted with KPA cells all survived with no detectable lung tumors. The gene expression profiles from cultured cell lines suggest oxidative stress as a potential vulnerability of KPA cells. Indeed, we found KPA cells were more sensitive to hydrogen peroxide and diethyl maleate-induced oxidative stress as compared to KP and KPS cells. Together, these results indicate that PIK3CA is not required for lung cancer cell growth induced by mutant KRAS in vitro but is essential for in vivo progression and growth. Full article

Background/Objectives: Static cold storage (SCS) remains the standard method of kidney preservation. As a referral transplant center, we frequently receive kidneys initially preserved with SCS and subsequently initiate prolonged hypothermic machine perfusion (HMP) to extend allocation time and optimize recipient matching. The clinical impact of this sequential preservation strategy remains incompletely defined. To compare outcomes between kidneys preserved with SCS followed by prolonged HMP (SCS+HMP) and SCS alone. Methods: This single-center retrospective study included 200 adult recipients of kidney transplants from brain-dead donors (67 SCS+HMP; 133 SCS). Outcomes were primary graft non-function (PNF), delayed graft function (DGF), patient and death-censored graft survival, and renal function over 24 months. Univariable and multivariable analyses identified predictors of DGF. Propensity score matching was performed to adjust for baseline imbalances. Results: In the SCS+HMP group, grafts underwent a median of 244 min of SCS followed by 1300 min of HMP, resulting in longer total cold ischemia time than SCS alone (1545 vs. 1104 min; p < 0.001). After matching, 51 pairs (n = 102) were analyzed. In the matched cohort, PNF occurred in 2 patients (3.9%) in the SCS+HMP group and 3 patients (5.9%) in the SCS group (p = 1.0). DGF occurred less frequently in the SCS+HMP group than in the SCS group (17.6% vs. 39.2%; p = 0.027). In multivariable Firth penalized logistic regression, HMP was independently associated with lower odds of DGF (OR 0.34; 95% CI 0.13–0.82). During the 24-month follow-up, patient survival, death-censored graft survival, and creatinine trajectories were comparable between groups. Conclusions: Sequential HMP after initial SCS enables extended preservation and was associated with a lower incidence of delayed graft function. This strategy does not compromise patient survival, death-censored graft survival, or renal function at 24 months. Full article

Stroke remains a leading cause of death and disability worldwide, imposing significant burdens on patients, families, and healthcare systems. Despite advances in acute management and rehabilitation, effective interventions to promote neural recovery remain limited. Hyperbaric oxygen therapy (HBOT) has emerged as a potential adjunctive treatment, but its effects on cortical functional activity—particularly the neurophysiological mechanisms underlying clinical improvements—remain insufficiently understood. This study aimed to investigate the effects of hyperbaric oxygen therapy (HBOT) on cerebral activation in stroke patients using functional near-infrared spectroscopy (fNIRS) and to evaluate its therapeutic efficacy. A total of 23 patients with intracerebral hemorrhage and 20 with cerebral infarction were enrolled. fNIRS data were collected before HBOT and within 10–30 min after treatment completion. During data acquisition, participants performed an alternating left- and right-hand grip task while wearing the fNIRS device throughout the procedure. Changes in near-infrared light intensity were monitored to objectively reflect cortical activity. The results showed that after HBOT, activation patterns in relevant brain regions during the grip task were significantly altered: activation channels during the bilateral grip task changed in cerebral infarction patients, with some brain regions overlapping with those observed in intracerebral hemorrhage patients. In intracerebral hemorrhage patients, the number of significantly activated channels decreased during the left-hand grip task but increased notably during the right-hand grip task, which may be related to cerebral functional compensation and right-hand dominance. Clinical assessments revealed significant post-treatment improvements in Brunnstrom stage, Fugl-Meyer scores, and activities of daily living. These findings suggest that HBOT may contribute to multifaceted recovery of brain function in stroke patients, not only by enhancing cerebral blood flow and oxygenation but also by facilitating neural repair and regeneration, as well as optimizing cerebral activation and functional connectivity. Thus, this study provides an objective basis for understanding the mechanisms and efficacy of HBOT in stroke rehabilitation. Full article

Persistent HIV reservoirs in long-lived macrophages pose a unique and formidable challenge to achieving HIV cure. HIV-infected macrophages are more resistant than CD4+ T cells to both virus- and immune-mediated death pathways including apoptosis, facilitating their persistence in tissue sanctuary sites and potential to contribute to viral rebound upon therapy cessation. This resistance is driven by HIV-induced modulation of both intrinsic and extrinsic apoptotic pathways, alongside survival mechanisms including autophagy. In this review, we examine the biological mechanisms promoting macrophage survival and explore novel translational strategies aimed at subverting this resistance. Crucially, we highlight the methodological limitations hindering progress, including the scarcity of robust in vitro macrophage models, the influence of culture conditions, and physiological relevance to macrophages in vivo. We emphasise that a macrophage-inclusive approach, incorporating improved pre-clinical models and developing clinical measurements to quantify the reservoir in human tissue, is essential to successfully eliminate this distinct reservoir and advance toward sustained ART-free remission. Full article

Background: Hepatorenal syndrome (HRS) is a severe complication of liver cirrhosis, marked by rapid renal function decline and poor prognosis. Although clinical predictors of HRS outcomes have been extensively studied, less is known about how demographic factors influence mortality patterns. Methods: This analysis utilized CDC WONDER data to assess U.S. mortality trends for hepatorenal syndrome (HRS) in adults aged ≥25 years from 1999 to 2024. We calculated crude mortality rates (CMR) and age-adjusted mortality rates (AAMR) per 100,000 and analyzed temporal trends using Joinpoint regression to determine the annual percentage change (APC) and average annual percentage change (AAPC). Results: From 1999 to 2024, 118,894 HRS-associated deaths were recorded. The overall AAMR decreased significantly from 2.43 in 1999 to 2.12 in 2024, with an AAPC of (AAPC −0.69% [95% CI: −0.90% to −0.51%]). Males consistently exhibited higher AAMRs than females (Males: 2.62 vs. Females: 1.63 in 2024). When stratified by race, the highest AAMR in 2024 was observed among non-Hispanic (NH) American Indian or Alaska Native populations (11.02), followed by Hispanic or Latino (2.58), NH White (2.23), NH Black or African American (1.30), and NH Asian or Pacific Islander populations (0.72). Regionally, the highest mortality was observed in the West, followed by the Midwest, South, and Northeast (2.88, 2.00, 1.92, and 1.53, respectively, in 2024). Rural areas (2.44) consistently exhibited higher AAMRs than urban areas (1.91) throughout the study period. Conclusions: HRS-related mortality has decreased modestly in the U.S over the last 26 years, yet significant inequities remain across population subgroups and regions. Mortality is disproportionately higher among males, NH American Indian or Alaska Native individuals, and residents of rural and western areas, highlighting the continued necessity for focused public health strategies. Full article

As a critical review and theoretical reflection, this study explores the transformation of funeral rites in contemporary Korean society and analyzes how ‘Filial Piety,’ a core Confucian value, has been reshaped by the mechanisms of medicalization and capitalism. Traditionally, in the Confucian worldview, death was not a biological termination but a religious process of advancing toward immortality through descendants’ ‘remembrance and representation.’ This paper identifies ‘cultural hybridity,’ where contemporary Korean funerals combine various religious traditions such as Christianity and Buddhism with secular forms, as positive evidence that the aspiration for spiritual bonds still persists. On the other hand, it establishes that the primary cause of damaging the public significance of death is not this mixture of rituals but ‘funeral capitalism’ based on market logic and medicalization. The study criticizes the fact that capitalist secularity has replaced the practice of Filial Piety with ‘reified consumption,’ thereby excluding those lacking economic means from the process of death. Conclusively, this study suggests the restoration of ‘spiritual publicness’ based on non-material continuing bonds and communal mourning, rather than material display. Full article

Breast cancer (BC) remains a major global health burden, consistently standing as the foremost contributor to cancer-related illness and death among women across the world. This meta-analysis aimed to evaluate the diagnostic accuracy of AI-assisted ultrasound elastography (UE) for BC detection by considering various factors, such as AI models, segmentation, cross-validation, data augmentation, the evaluation phase, and the addition of conventional ultrasound. PubMed, Cumulative Index to Nursing and Allied Health Literature, Embase, Scopus, and Web of Science were searched from inception to 22 June 2025, for observational studies using any AI-aided UE modality in BC classification compared to histopathology. We extracted binary diagnostic accuracy data and employed the split component synthesis method for pooled outcomes. Out of 501 identified records, 39 studies (6191 samples) were included in the meta-analysis. The overall diagnostic performance showed 90.3% sensitivity (95% confidence interval [CI] 86.4–93.1%), 88.0% specificity (95% CI 83.6%–91.4), a positive likelihood ratio of 7.5 (95% CI 5.4–10.5), a negative likelihood ratio of 0.110 (95% CI 0.078–0.156), and a diagnostic odds ratio of 68.3 (95% CI 42.3–110.1). Heterogeneity was substantial (I² = 78.0%), and the funnel plot demonstrated mild positive asymmetry. Subgroup analyses indicated improved diagnostic performance in studies that employed automatic or no segmentation, cross-validation, data augmentation, retrospective designs, models evaluated during the training phase, classical machine learning approaches, and the combination of B-mode ultrasound with elastography. Despite the presence of heterogeneity and the possibility of overestimation, AI-aided UE demonstrated superior diagnostic performance compared to UE alone. Researchers should consider adopting automatic segmentation, cross-validation, augmentation, and combining UE with conventional ultrasound. Our meta-analysis also explored the potential integration of AI-aided UE into breast cancer screening practices. Full article

Background/Objectives: Acute heart failure (AHF) is a leading cause of hospitalization and mortality among very old patients, yet this group is underrepresented in prognostic studies. Carbohydrate antigen 125 (CA125) has emerged as a potential biomarker of congestion and inflammation, but its value in patients aged 80 years and over remains unclear. We aimed to evaluate the prognostic value of plasma CA125 measured at admission for 12-month all-cause mortality and the composite outcome of mortality or heart failure (HF) readmission in very elderly patients hospitalized for AHF. Methods: We conducted a prospective observational study of patients aged ≥80 years admitted to an acute geriatric unit for AHF. CA125 and NT-proBNP were measured within 24 h of admission. Outcomes were assessed at 12 months. Survival analyses were performed using Kaplan–Meier curves, Cox regression models, and restricted cubic splines. Results: A total of 210 patients (mean age 89.8 ± 5.3 years; 75.3% females; 88.1% frail) were recruited. During the one-year follow-up, 70 deaths (37.2%) and 68 HF hospital readmissions (36.1%) were recorded. Patients in the highest CA125 tertile had an increased cumulative mortality risk (log-rank p = 0.061). A CA125 value ≥ 100 U/mL independently predicted both mortality (HR 1.88, 95% CI 1.15–3.09; p = 0.012) and the composite endpoint (HR 1.54, 95% CI 1.04–2.29; p = 0.031). Measures of functional dependence and frailty demonstrated greater discriminative ability than biomarkers. Conclusions: In very elderly patients hospitalized for AHF, elevated CA125 at admission independently predicted 12-month mortality and HF readmission. CA125 provides complementary prognostic information to geriatric assessment and may support risk stratification in this vulnerable population. Full article

Studies that have sought to describe and account for pre-diagnosed depressive symptoms on BC treatment choice, delay in initiating treatment, and mortality have been inconsistent. The purpose of the study is to examine the association between pre-diagnosed depressive symptoms and their impact on breast cancer (BC) treatment, treatment delays, and mortality. We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results–Medicare Health Outcomes Survey (SEER-MHOS) dataset among women aged 65 years and older diagnosed with BC. Among 3840 eligible patients, 28.1% had pre-diagnosed depressive symptoms. Patients with pre-diagnosed depressive symptoms who were diagnosed with early-stage BC were significantly more likely (OR = 1.52; 95% CI: 1.26–1.84) to undergo mastectomy or receive breast-conserving surgery (BCS) alone rather than BCS plus radiation therapy (RT) compared to patients who were not pre-diagnosed with depressive symptoms. Among patients with advanced-stage BC, pre-diagnosed depressive symptoms were not significantly associated with treatment type. Among Hispanic patients, pre-diagnosed depressive symptoms were associated with treatment delays. Overall, patients with pre-diagnosed depressive symptoms had a 16% increased adjusted risk of BC-related mortality compared to those who were not pre-diagnosed with depressive symptoms, and those with advanced-stage cancer had an 18% higher adjusted risk of death than early-stage BC. Conclusions: Overlooking depressive symptoms management prior to a breast cancer diagnosis may result in poorer survival outcomes. Early detection and consistent management of depression are critical for improving patient survival. Full article

Background: Sepsis remains a leading cause of mortality worldwide. This study evaluated the independent and combined effects of age and chronic comorbidities on clinical outcomes in patients with septic shock. Methods: We conducted a multicenter retrospective observational study to evaluate the factors associated with 28-day mortality in the Korean Shock Society registry between 2015 and 2023. Adults with suspected infection and refractory hypotension or hypoperfusion within 6 h of emergency department (ED) arrival were included. Patients were grouped by age (<50, 50–74, and ≥75 years) and comorbidity status. Comorbidities encompass major chronic conditions including hypertension, diabetes mellitus, malignancy, history of organ transplant, dementia, nursing home residence, chronic disease of cardiac, lung, liver, and kidney. The primary outcome was 28-day mortality. Multivariable logistic regression analysis was used. Results: Among 8787 patients (median age 70.2 years), the 28-day mortality rate was 22.9% (n = 2018). Elderly patients with comorbidities had the highest mortality (27.5%). Additionally, patients aged over 50 with at least one comorbidity accounted for 18% of the total cohort (n = 1605) but accounted for nearly 80% of all 28-day deaths. Although younger patients without comorbidities represented a small subgroup, their mortality was not negligible (7.3%) and was substantially higher with comorbidities (22.2%). Compared with patients <50 years, adjusted odds ratios (aORs) of 28-day mortality were 1.81 (95% CI, 1.08–3.03) for 50–74 years and 3.21 (95% CI, 1.92–5.37) for ≥75. The presence of any comorbidities was independently associated with higher odds of 28-day mortality compared with no comorbidity (aOR 2.67; 95% CI, 1.57–4.54). A significant interaction between age and comorbidity status (p for interaction = 0.008) suggested that the age-related gradient in mortality differed depending on comorbidity burden. Conclusions: Age and comorbidities were both significantly associated with septic shock mortality, and their significant interaction demonstrates effect modification, indicating that the prognostic impact of comorbidities differs by age group and that age-related mortality gradients are influenced by comorbidity burden. Full article

Diverse natural systems in the universe from stars to organisms have finite “life cycles” (durations of existence). In my review, I attempt to answer fundamental but little explored questions about birth-death cycles, including “why do they exist?”, “what do they have in common?”, and “how/why do they vary?” Various physical and biological systems have life cycles because they cannot avoid “death”, metaphorically speaking. Thus, if their type is to persist, they must replace themselves. All systems with life cycles are dissipative structures with a generative phase of growth and increasing order driven by energy uptake/use and a degenerative phase of degrowth and decreasing order driven by entropy production and accidental damage. Life cycles vary in rapidity and duration, often in relation to system size. The life cycles of living systems also differ from those of non-living systems in using information to regulate their birth and death, at least in part. Living systems are born via self-production, whereas non-living systems are “born” de novo. Thus, living systems perpetuate themselves by means of branching ancestor–descendant lineages, thereby enabling the cumulative evolution of their relatively high levels of diversity and complexity. Living systems (from cells to societies) are also extraordinary in having multi-layered compound cycles, i.e., “cycles within cycles”. Based on my comparative analysis of living and non-living systems across the universe, I propose a preliminary, multi-mechanistic theory of life cycles and their origins. Full article

Conjugated linolenic acids (CLnAs) are emerging as promising agents to trigger ferroptosis, a cell death driven by excessive lipid peroxidation, in cancer cells. Given the aggressive nature and treatment resistance of malignant melanoma, exploring CLnAs as therapeutic agents may offer a novel strategy to overcome these challenges. Here, we investigated the toxicity of four CLnA isomers on human (A375, WM266.4) and zebrafish (ZMEL1) melanoma cell lines. We observed a dose-dependent reduction in cell viability across all three tested cell lines. While human melanoma cells were more sensitive to CLnAs than ZMEL1 cells, treatment with ferroptosis inhibitors mitigated cell death in all models, confirming ferroptosis as the consistent primary mechanism of cell death. In addition, chemical inhibitors of ACSL4 and GPX4 modulated CLnA toxicity, further substantiating the ferroptotic mechanism by highlighting the role of these key regulators. Furthermore, fatty acid analysis revealed that CLnAs were effectively incorporated into phospholipids, generating substrates for lethal lipid peroxidation. At the transcriptional level, CLnA treatment significantly upregulated the pro-ferroptotic gene acsl4a in ZMEL1 cells. Overall, our study identifies specific CLnAs as potent ferroptosis inducers in both human and zebrafish melanoma cells and underscores the translational relevance of the zebrafish model based on a shared ferroptotic mechanism. Full article