Therapeutic Intervention Research Articles

Predictors of poor prognosis in long-term survivors of differentiated thyroid cancer with psychiatric disorders

BACKGROUND Thyroid malignancies, while accounting for a small proportion of cancer diagnoses globally, have demonstrated a consistent upward trend in occurrence across diverse populations, with gender-specific analyses revealing a disproportionate burden among women. Despite the characteristically indolent nature of most thyroid carcinomas and their associated high survival rates, emerging evidence points to significant unmet needs regarding psychosocial adaptation and neuropsychiatric sequelae in this growing survivor population. The spectrum of mental health conditions, ranging from affective and anxiety disorders to cognitive impairments, presents substantial barriers to functional recovery and may potentially influence disease trajectories through complex psychoneuroimmunological pathways. Clinical observations consistently report elevated rates of mood disturbances and executive function deficits persisting throughout the cancer continuum, from active treatment into extended follow-up periods. These findings highlight a critical knowledge gap in understanding the dynamic interplay between thyroid cancer biology, its therapeutic interventions, and the development of treatment-resistant psychiatric manifestations that complicate long-term patient care. AIM To analyse the factors influencing the poor prognosis of patients surviving long-term differentiated thyroid cancer with psychiatric disorders and to construct a prediction model. METHODS Forty-eight patients with mental disorders combined with differentiated thyroid cancer who were treated in our hospital during the period of March 2018 to March 2023 were retrospectively selected as the study subjects (thyroid cancer group), and 30 cases each of patients with mental disorders combined with benign thyroid nodules (benign nodules group) and patients with mental disorders alone (mental disorders group), who were treated during the same time period, were selected as controls. The patients with differentiated thyroid cancer were further divided into a poor prognosis group (10 cases) and a good prognosis group (38 cases). The study outcome was poor prognosis as shown by whole body bone imaging within 2 years after thyroid cancer surgery. Factors influencing poor prognosis in survivors of differentiated thyroid cancer were analyzed by univariate and multivariate logistic regression analyses, receiver operating characteristic (ROC) curve analysis was used to assess the predictive efficacy of these factors for poor prognosis, and the DeLong test was used to determine whether there was a statistically significant difference in the area under the curve (AUC) of the model. RESULTS One-way logistic regression analysis showed that tumour diameter [odds ratio (OR) = 19.190, P = 0.002], T-stage (OR = 7.692, P = 0.018), extra-glandular infiltration (OR = 37.000, P = 0.003), degree of differentiation (OR = 24.667, P = 0.008), serum free T3 (OR = 22.348, P = 0.025), serum free T4 (FT4) (OR = 1.158, P = 0.002), total bilirubin (TBil) (OR = 1.792, P = 0.004), albumin (OR = 0.675, P = 0.003), cortisol (OR = 1.180, P = 0.003), norepinephrine (OR = 1.047, P = 0.002), angiotensin II (OR = 1.975, P = 0.002), and superoxide dismutase (OR = 0.515, P = 0.005) all increased the risk of poor prognosis in patients with psychiatric disorders and long-term differentiated thyroid cancer. Multifactorial logistic regression analysis showed that tumour diameter (OR = 16.570, P = 0.021), extra-glandular infiltration (OR = 53.145, P = 0.010), FT4 (OR = 1.186, P = 0.007), and TBil (OR = 2.823, P = 0.048) were independent risk factors for poor prognosis of patients with psychiatric disorders with long-term differentiated thyroid cancer, and the regression equation was: Y = 2.808 × tumour diameter + 3.973 × extra-glandular infiltration + 0.171 × FT4 + 1.038 × TBil - 88.138. ROC analysis showed that the predictive power of the overall model (AUC = 0.992, P = 0.000) was significantly higher than that of independent risk factors (DeLong test P < 0.05). CONCLUSION Tumour diameter, extra-glandular infiltration, FT4, and TBil are independent risk factors for poor prognosis in patients with psychiatric disorders with long-term differentiated thyroid cancer, and the combination of these factors is of higher value in predicting the prognosis of patients. These risk factors can be used as a basis to develop a reasonable prognostic management plan in clinical practice for patients with long-term differentiated thyroid cancer with mental disorders, so as to improve the prognosis and quality of life of patients.

Beyond obesity: lean metabolic dysfunction-associated steatohepatitis from unveiling molecular pathogenesis to therapeutic advancement.

Nonalcoholic fatty liver disease (NAFLD), now known by the name of metabolic dysfunction-associated fatty liver disease (MAFLD), with increased global incidence, has been recognized as a significant metabolic disorder. NAFLD includes a spectrum liver disease from hepatocellular fat accumulation (isolated steatosis) to an advanced form of liver injury known as nonalcoholic steatohepatitis (NASH), which refers to distinct histologic features, including hepatocellular steatosis and injury, necroinflammation, and eventually fibrosis. Nonobese or lean individuals associated with metabolic dysregulation usually demonstrated diverse risk factors compared to obese MAFLD. The presence of normal range body mass index (BMI) and excess visceral adiposity with increased cardiometabolic and renal comorbidities, along with sarcopenia, has been evidenced to be associated with lean MASH. Genetic predispositions accompanying lifestyle and environmental factors contribute to disease initiation and progression. The genetic influence in pathophysiology indicated the significant contributions of the following genes: PNPLA3, TM6SF2, APOB, LIPA, MBOAT7, and HSD17B13, and the impact of their disease-specific variants in the development of obesity-independent MASH. The epigenetic modifications exhibited differential DNA methylation patterns in the genes involved in lipid metabolism, particularly hypomethylation of PEMT. Diet-induced and genetic animal models of lean MASH, including Slc: Wistar/ST rats, PPAR-α, PTEN, and MAT1A knockout mice models, are indicated to be pivotal in the exploration of disease progression and observing the effect of therapeutic interventions. This comprehensive review comprises the molecular and genetic pathophysiology, molecular diagnostics, and therapeutic aspects of lean MASH to enunciate a diagnostic approach that combines detailed clinical phenotyping regarding genomic analysis.

Formulation and Optimization of Pyrazinamide-Loaded Solid Lipid Nanoparticles by Employing a Design of Experiments Approach.

Tuberculosis (TB) remains a major worldwide health challenge causing morbidity and mortality, necessitating novel approaches for its effective therapy. Pyrazinamide (PYZ), a nicotinamide analogue, is a key frontline drug significantly involved in the treatment of TB. However, its dose-dependent hepatotoxicity is a major concern that needs to be addressed. The aim of the current research was to develop PYZ-loaded solid lipid nanoparticles (PYZ-SLNs) as a potential therapeutic intervention for treating TB. The PYZ-SLNs were formulated by a high-pressure homogenization technique and optimized using a 23-factorial design. The drug concentration, emulsifier concentration, and homogenization cycles were considered critical formulation and processing parameters to study their effects on essential attributes of quality of PYZ-SLNs, i.e., entrapment efficiency (EE%), drug loading (DL%), and particle size. The optimized PYZ-SLNs showed a particle size of 401±08 nm, EE% of 86.24±1.15, DL% of 14.38±0.85. The in vitro lipolysis studies revealed that PYZ-SLNs exhibited an anti-lipolytic effect due to stabilization by poloxamer 188. Moreover, the in vitro gastrointestinal (GI) stability results demonstrated that the PYZ-SLNs were stable in GI tract media (at pH 1.2, pH 4.5, pH 6.8, and pH 7.4). The in vitro drug release studies showed the best fit with the Hixon-Crowell model. The accelerated stability studies revealed no significant changes in PYZ-SLNs for 6 months. PYZ-SLNs could be a promising carrier for the treatment of TB via the oral intestinal lymphatic pathway, circumventing its hepatic first-pass metabolism and thereby preventing hepatic adverse effects.

Engineered Hydrogels for Organoid Models of Human Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is characterized by increased lipid accumulation and excessive deposition of extracellular matrix (ECM) that results in tissue stiffening. The potential interplay between matrix stiffness and hepatocyte lipid accumulation during NAFLD has not been established. Here, an in vitro NAFLD model is developed using chemically defined, engineered hydrogels and human induced pluripotent stem cell-derived hepatic organoids (HOs). Specifically, dynamic covalent chemistry crosslinking, along with transient small molecule competitors, are used to create dynamic stiffening hydrogels that enable the reproducible culture of HOs. Within matrices that mimic the stiffness of healthy to diseased tissue (≈1-6kPa), lipid droplet accumulation in HOs is triggered by exposure to an NAFLD-associated free fatty acid. These NAFLD model suggests that higher stiffness microenvironments result in increased hepatic lipid droplet accumulation, increased expression of fibrosis markers, and increased metabolic dysregulation. By targeting the ROCK mechanosignaling pathway, the synergy between matrix stiffness and lipid droplet accumulation is disrupted. The in vitro model of NAFLD has the potential to understand the role of mechanosignaling in disease progression and identify new pathways for therapeutic intervention.

Calcium-binding protein 39 in with-no-lysine kinase signaling and the modulation of renal tubular transport.

The regulation of renal tubular transport is essential for maintaining electrolyte balance and blood pressure. Calcium-binding protein 39 (Cab39), also known as mouse protein-25 (MO25), plays a pivotal role in modulating this process through its interaction with WNK (with no lysine) kinases and Ste20-like kinases, including STE20/SPS1-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1). By stabilizing and facilitating the activation of these kinases, Cab39 plays a crucial role in the regulation of key ion transporters, such as the sodium-chloride cotransporter (NCC) and the sodium-potassium-chloride cotransporters (NKCC1 and NKCC2). This review provides a comprehensive analysis of Cab39 structural properties, molecular interactions, and functional roles in renal physiology, emphasizing its significance in ion homeostasis. Studies reveal that Cab39 enhances SPAK activity up to 100-fold. Importantly, the role of Cab39 extends beyond simple kinase activation, as it supports kinase complex assembly and localization, enabling precise control over transporter regulation. Evidence also suggests that Cab39 may influence the regulation of NCC and NKCC2 through similar mechanisms, making it a promising target for therapeutic interventions in disorders such as hypertension and salt-wasting syndromes. The discovery of a small-molecule Cab39 inhibitor highlights its potential as a pharmacological target. Understanding the multifaceted functions of Cab39 may unlock novel strategies for managing renal and cardiovascular disorders.

Effects of Ninjin’yoeito and physical exercise on serum corticosterone and hippocampal BDNF/proBDNF and neuroinflammation in post-stroke depression in rats

BackgroundNinjin’yoeito (NYT), a traditional Japanese Kampo medicine, improves the depression and anxiety in humans and animals, rendering it a novel therapeutic option for post-stroke depression (PSD). Furthermore, physical exercise is an important nonpharmacological therapy for major depressive disorder. The components of NYT or exercise exert antidepressant effects through the increased expression of neurotrophic factors and reduced neuroinflammation in the brain. However, the mechanisms underlying the antidepressant effects of NYT and exercise in PSD remain unclear. Therefore, we examined the effects of NYT and physical exercise in a rat model of PSD.MethodsRats were divided into five groups: PSD, PSD with NYT, PSD with exercise (Ex), PSD with NYT and exercise (NYT + Ex), and control (sham). PSD was induced by the microinjection of endothelin-1 into the left medial prefrontal cortex and chronic unpredictable mild stress 3 days per week. A diet containing 3% NYT was administered to rats one day after stroke induction. Exercise was conducted using a motorized treadmill for three days per week, starting three days after the stroke. The therapeutic interventions lasted for four weeks. Serum corticosterone levels, depression-like behavior, and hippocampal pathophysiology, including the expression of brain-derived neurotrophic factor (BDNF), precursor BDNF (proBDNF), doublecortin (DCX), NeuN, glial cell activation, and tumor necrosis factor-α (TNF-α), were examined.ResultsSerum corticosterone levels were lower in the treatment group than those in the PSD group. Notably, serum corticosterone levels were significantly lower in the NYT group than those in the PSD group. BDNF expression in the CA1 region was significantly higher in the Ex group than that in the PSD group. The NYT + Ex group showed a significantly higher hippocampal BDNF/proBDNF ratio than the other groups. DCX and NeuN expression levels were significantly higher in the NYT + Ex group than those in the NYT and PSD groups. Hippocampal glial cell activation and TNF-α expression increased in the PSD group and decreased in the intervention groups.ConclusionsNYT ameliorates serum corticosterone levels and hippocampal neuroinflammation in PSD. Additionally, this study suggested that NYT, together with exercise therapy, may improve neurogenesis, the BDNF/proBDNF ratio, and neuroinflammation in the hippocampus in PSD.Clinical trial numberNot applicable.

Translational approach to ventricular innervation: the posterior descending ganglionated plexus.

Modulation of cardiac neural control is increasingly explored to treat cardiac arrhythmias. While the atrially located ganglionated plexus (GPs) have been studied intensively, characterization of ventricular GPs is sparse. This proof-of-principle study aimed to assess the role of the posterior descending GP (PDGP) for neural control of cardiac electrophysiology, while offering a translational roadmap into clinical practice. Since an initial systematic literature review revealed the PDGP as a small, consolidated GP on the posterior left ventricle in dogs, swine and humans, we subsequently conducted morphological C57BL/6 murine studies (n=43) indicating ventricular GPs in only 10% of hearts. Based on our initial findings, in a proof-of-principle study analyzing 4,300 local unipolar electrograms from a multi-electrode sock, the impact of functional PDGP modulation was studied in an ex-vivo retrograde-perfused porcine model. Wave propagation characteristics determined by epicardial activation mapping demonstrated increased dispersion of conduction velocity during high-frequency (8.52±2.24 radian vs. 2.79±0.89 radian; P=0.018) and nicotine stimulation (19.79±6.49 radian vs. 2.79±0.89 radian; P=0.044) compared to paced rhythm. High-frequency stimulation prolonged activation recovery intervals in the posterior (257.8±6.7 ms vs. 244.8±1.9 ms; P=0.044) and basal (258.1±4.2 ms vs. 244.8±1.9 ms; P=0.039) right ventricle compared to the posterior left ventricle. Analysis of explanted human hearts confirmed the presence of the PDGP within epicardial adipose tissue near its eponymous coronary artery and the posteromedial left atrial GP. Three-dimensionally reconstructed human hearts suggested the PDGP localization characterized by interpatient anatomical variability. The present translational approach to ventricular innervation demonstrates first evidence of the functional relevance of the PDGP, with morphological findings indicating species-related differences. Novel imaging modalities might pave the way for future functional and therapeutic interventions.

EVALUATING THE ROLE OF SOCIAL WORK IN MITIGATING CHILDHOOD TRAUMA: CASE STUDIES FROM FOSTER CARE FACILITIES IN THE USA

Childhood trauma, often categorized under the concept of Adverse Childhood Experiences (ACEs), refers to potentially harmful events or environments that disrupt a child's sense of safety and stability during early development. Adverse Childhood Experiences (ACEs) significantly impact emotional, mental, and physical well-being, increasing the risk of chronic health conditions, behavioral disorders, and long-term developmental challenges. Foster care facilities play a vital role in mitigating the effects of childhood trauma, with social workers acting as key facilitators in fostering recovery and resilience. Trauma-informed care (TIC) has gained recognition as an essential framework in child welfare systems, emphasizing safety, trust, collaboration, and empowerment in therapeutic interventions. This study evaluates the role of social work in mitigating childhood trauma within U.S. foster care facilities by analyzing case studies that demonstrate best practices, challenges, and outcomes. Findings indicate that social workers implementing trauma-informed interventions, such as cognitive-behavioral therapy (CBT), art therapy, and peer support programs, significantly improve emotional regulation and reduce symptoms of post-traumatic stress disorder (PTSD) among foster children. However, challenges persist, including high caseloads, funding constraints, limited access to mental health services, and systemic placement instability. The study highlights the need for increased funding, standardized training in TIC for social workers, and stronger community partnerships to enhance trauma recovery efforts. Adopting holistic and culturally responsive approaches, foster care systems can create supportive environments promoting resilience and emotional well-being among vulnerable children. This research contributes to the discourse on improving child welfare policies and the effectiveness of social work in addressing childhood trauma. Keywords: Childhood Trauma, Foster Care, Social Work, Trauma Recovery, Adverse Childhood Experiences (Aces)

Exploring perspectives on how to improve psychological treatment for women from minoritised ethnic communities: qualitative study with psychological therapists.

Women from minoritised ethnic communities experience inequalities in access, experience and outcomes of psychological therapy. Understanding the factors associated with these inequalities could inform improvements to mental health services. To explore therapists' experiences of providing treatment to women from minoritised ethnic communities, including insights on adaptations made at the delivery, content and wider organisation levels, and to gather suggestions about potential treatment improvements. Semi-structured interviews were conducted with 13 therapists working in two National Health Service Talking Therapies for anxiety and depression services and who had experience of treating women from minoritised ethnic communities. Data were analysed using thematic analysis. Three high-order themes were identified: incorporating ethnicity and culture in the delivery of psychological therapies, challenges associated with delivering therapeutic interventions to women from minoritised ethnic groups and improvements to services that could support better access, engagement and outcomes for women from minoritised ethnic groups. Findings indicate that therapists viewed cultural adaptation and cultural sensitivity as important to the delivery of appropriate care for minoritised ethnic women. Challenges to appropriate care included limited service resources, communication and language barriers, stigma and existing access and engagement inequalities. Therapists suggested that, to deliver high-quality care and optimise outcomes, improvements are required in cultural sensitivity training, flexibility of service delivery, outreach work with communities to encourage uptake and reduce stigma, support for staff and workforce diversity.

Analysis of raltegravir analogs to enhance inhibitory efficiency against HIV integrase

This article addresses the improvement of the efficacy of anti-integrase enzyme drugs for the AIDS virus, especially using the drug Raltegravir and its 21 analogs. In this research, Hartree-Fock and Density Functional Theory methods have been employed for the design and optimization of new drug candidates. These methods are used to enhance the accuracy and reactivity of the drugs. Additionally, docking is used to investigate the interactions between the drug and the target and evaluate binding energies. Molecular dynamics simulation is utilized to validate binding results. Computational results indicate that the designed analogs exhibit higher reactivity. In molecular docking calculations, RAL5 and RAL21 show the best binding energies of -10.10 and − 10.92 kcal/mol, respectively, indicating their superior efficiency. The analysis of inhibitor potentials against the HIV-1 integrase enzyme through molecular dynamics simulation reveals that RAL5 has strong inhibitory potential for treating viral diseases. These findings contribute to the promotion of therapeutic intervention methods in this field.

Sarcopenia and clinical outcomes in lymphoma and multiple myeloma patients receiving hematopoietic cell transplantation: a systematic review and meta-analysis.

Sarcopenia, characterized by skeletal muscle loss, is increasingly recognized as a predictor of poor outcomes in hematologic malignancies. This study evaluated the impact of sarcopenia on survival and post-transplant outcomes in lymphoma and multiple myeloma patients undergoing hematopoietic cell transplantation (HCT). A systematic review of eleven retrospective studies (2015-2024) including 1866 patients was conducted. Sarcopenia was assessed by CT, with some variation in diagnostic criteria. Pooled analyses were conducted to examine associations with mortality, progression-free survival (PFS), and non-relapse mortality (NRM). The overall prevalence of sarcopenia was 45.7% (lymphoma: 44.2%, multiple myeloma: 49%). Sarcopenia significantly increased mortality risk in lymphoma (HR 1.92, 95% CI 1.61-2.29, p < 0.00001) and multiple myeloma patients (HR 1.12, 95% CI 1.03-1.22, p = 0.01). PFS was worse in lymphoma patients (HR 2.40, 95% CI 1.44-4.36, p = 0.0009), but NRM did not differ significantly. Sarcopenia is a significant risk factor for poor outcomes in HCT recipients. Routine assessment and targeted interventions, including nutritional and exercise strategies, may improve patient outcomes. Further prospective studies are needed to establish standardized diagnostic criteria and explore therapeutic interventions.

TRIM23 mediates cGAS-induced autophagy in anti-HSV defense

The cGAS-STING pathway, well-known to elicit interferon (IFN) responses, is also a key inducer of autophagy upon virus infection or other stimuli. Whereas the mediators for cGAS-induced IFN responses are well characterized, much less is known about how cGAS elicits autophagy. Here, we report that TRIM23, a unique TRIM protein harboring both ubiquitin E3 ligase and GTPase activity, is crucial for cGAS-STING-dependent antiviral autophagy. Genetic ablation of TRIM23 impairs autophagic control of HSV-1 infection. HSV-1 infection or cGAS-STING stimulation induces TBK1-mediated TRIM23 phosphorylation at S39, which triggers TRIM23 autoubiquitination and GTPase activity and ultimately elicits autophagy. Fibroblasts from a patient with herpes simplex encephalitis heterozygous for a dominant-negative, kinase-inactivating TBK1 mutation fail to activate autophagy by TRIM23 and cGAS-STING. Our results thus identify the cGAS-STING-TBK1-TRIM23 axis as a key autophagy defense pathway and may stimulate new therapeutic interventions for viral or inflammatory diseases.

Human dental pulp stem cells attenuate airway inflammation in mice with PM2.5-induced asthma exacerbation by inhibiting the pyroptosis pathway

BackgroundFine particulate matter (PM2.5) exposure significantly exacerbates respiratory morbidity, particularly in asthmatic individuals, highlighting an urgent need for effective therapeutic interventions. In this study, we evaluated the therapeutic potential and underlying mechanisms of human dental pulp stem cells (hDPSCs), a promising mesenchymal stem cell population, in mitigating airway inflammation in mice with PM2.5-induced asthma exacerbation.MethodsIn a PM2.5-exacerbated ovalbumin (OVA)-asthma murine model, hDPSCs were intravenously administered with MCC950 (NLRP3 inhibitor) as positive control, systematically evaluating their therapeutic effects on airway inflammation and pyroptosis through pulmonary function tests, histopathological examination, cytological and molecular analyses.ResultsThe administration of hDPSCs ameliorated airway inflammation. Moreover, hDPSCs further alleviated Th2 inflammation and decreased serum IgE concentrations, along with a decrease in eosinophils in BALF. At the same time, interleukin-1β (IL-1β) and IL-18 levels in BALF and caspase-1 activity in lung tissues were reduced. In addition, immunohistochemistry showed that the expression levels of NLRP3, caspase-1, GSDMD, cleaved capsase-1 and IL-1β were reduced. The western blot results also showed that the expression level of NLRP3/caspase-1/GSDMD/cleaved capsase-1 in the classical pathway of pyroptosis decreased after hDPSCs intervention.ConclusionsThese findings provided the first evidence that hDPSCs transplantation attenuated allergic airway inflammation and mucus secretion in mice with PM2.5-induced asthma exacerbation. Thus, hDPSCs exert these protective effects through suppression of the NLRP3/caspase-1/GSDMD-mediated pyroptosis pathway, suggesting their potential as a novel cell-based therapy for PM2.5 inhalation-mediated asthma.

E-cadherin expression in the tongue epithelium of streptozotocin-induced diabetic rats: an exploratory study.

Little was found on the association between diabetes and its effect on epithelial intercellular adhesion. However, no study reported the association between hyperglycemia and E-cadherin-mediated cell adhesion in tongue epithelium. This study aimed to explore the potential impacts of hyperglycemia on the epithelial E-cadherin expression in the tongue's epithelial tissue in streptozotocin (STZ)-induced diabetic rats. Twelve male Wistar albino rats were randomly allocated into control and STZ-induced diabetic groups. At the 5-week post-STZ injection, rats were euthanized, and the tongues were harvested and preserved in formalin. Epithelial thickness was assessed using hematoxylin and eosin (H&E) staining, while immunohistochemistry (IHC) was employed to analyze the expression of E-cadherin. Statistical analysis was performed using unpaired t-tests and two-proportion Z-tests, with a significance level determined at p < 0.05. The results showed a significant reduction in epithelial thickness in the dorsal tongue of STZ-diabetic rats compared to the control group (p = 0.0173). Additionally, E-cadherin expression in the dorsal tongue epithelium was markedly weaker in the diabetic group than in the control (p < 0.0001). This exploratory study is the first to report that hyperglycemia reduces E-cadherin expression in the dorsal tongue epithelium, possibly contributing to oral epithelial alterations observed in diabetes. These findings not only highlight the potential diagnostic value of E-cadherin as a biomarker for oral complications in diabetic patients but also provide a foundation for future translational and clinical studies exploring therapeutic interventions targeting epithelial integrity in diabetes.

Targeting the Hippo pathway for cardiac regeneration.

Ischemic heart disease, which affects more than 200 million people worldwide, is caused by reduced blood flow to the heart and leads to widespread cardiomyocyte death. Due to the limited regenerative potential of cardiomyocytes, the lost tissue is replaced by a fibrotic scar, resulting in reduced cardiac function and progression to heart failure. Current therapeutic interventions aim to improve blood flow, but cannot address the inability for cardiomyocytes to renew after injury. However, multiple studies have shown that modulating the Hippo signaling pathway to activate YAP, a transcription coactivator, in adult murine and porcine cardiomyocytes induces robust cardiomyocyte proliferation. Here, we discuss the therapeutic potential of YAP activation in the context of cardiac renewal, with focus on both cardiomyocyte intrinsic mechanisms and the role of the microenvironment. These findings provide important insights into cardiac regeneration and strategies for developing therapies for human patients.

Sleep-disordered breathing profiles in patients with cardiovascular diseases: Kurume SDB-CVD study

Sleep-disordered breathing (SDB) links to various cardiovascular diseases (CVDs), but comprehensive insights and detailed profiles remain scarce. This study examined the clinical characteristics of CVD patients complicated by SDB in the enrolled all consecutive 5765 patients who underwent screening tests for SDB during hospitalization from January 2014 to December 2019, using the database of Cardiovascular Medicine, Kurume University Hospital. Desaturation during sleep in SDB was significantly worse in terms of age, sex, daytime resting oxygen saturation (SpO2), systolic blood pressure (SBP), pulse pressure, body mass index (BMI), white blood cell count, hemoglobin A1c, serum creatinine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiothoracic ratio on chest X-ray, and left ventricular ejection fraction on echocardiography (all p-values < 0.001, except for SBP p = 0.002, and NT-proBNP p = 0.004). Coronary artery disease and heart failure, but not pulmonary hypertension, were associated with a higher prevalence and a greater risk of moderate to severe SDB, typically in older patients. Notably, low SpO2 during daytime and elevated BMI were indicative of SDB across all age categories for both sexes. Heatmaps of daytime SpO2 and BMI can effectively predict the severe SDB in patients with CVDs, suggesting the potential for efficient therapeutic interventions for SDB.

Presence: a facilitating condition, therapeutic intervention, and modifiable factor in Haptotherapy

This article examines presence in Haptotherapy through the lens of a three-day continuing education course. Presence is presented as a facilitating condition, a therapeutic intervention, and a modifiable element within Haptotherapy. Presence, in all its facets, plays an essential role in Haptotherapy. Haptotherapy distinguishes itself from other forms of therapy through the use of affective, contact-oriented therapeutic touch, which both invites the patient into presence and helps guide the way toward it. A shared foundational concept across all three haptotherapy training programs in the Netherlands is ‘feeling one’s way toward meaningful contact’. In this context, feeling is understood as an affective reaching out toward the other through the sense of touch, in which one simultaneously allows their enlivened presence to be felt, thereby inviting the other into affective contact. Further empirical research is needed to evaluate and refine the theoretical models underlying this process.

Ventilator-Associated Pneumonia in COVID-19 Patients: Prevalence and Associated Factors

Background: COVID 19 pandemic has resulted in increased ICU admission, with many patientsrequiring mechanical ventilation resulting in more incidences of ventilator associated pneumonia(VAP). Despite vast research on COVID 19 complications, very few studies have looked at the riskfactors of VAP in this population. The purpose of this study is to bridge this gap by identifying clinicaland laboratory predictors of VAP in critically ill COVID-19 patients. Methods: Shahid Beheshti Hospital, Kashan was the site of a retrospective analysis of 235 COVID 19ICU patients requiring mechanical ventilation. Therapeutic interventions were assessed and clinicalsymptoms, laboratory markers were assessed. Results: Fever and chills were also found to be associated with nearly a threefold increase in risk (p &lt;0.05) as was abnormal heart rate, which increased the risk fourfold (p &lt; 0.001), and WBC and ESRsignificantly correlated with VAP occurrence. In addition, patients not treated with tocilizumab had asixfold increase in risk of VAP (p &lt; 0.001). Early identification and targeted interventions to mitigatethe risk of VAP in COVID-19 patients being mechanically ventilated is a focus of this study. Conclusion: Results indicate immunomodulatory therapy may provide a protective role, andunderscore the importance of strict infection control. Future research should model causal mechanismsand develop best treatment strategies to reduce the incidence of VAP.

Development, Validation, and Deployment of a Time-Dependent Machine Learning Model for Predicting One-Year Mortality Risk in Critically Ill Patients with Heart Failure

Background: Heart failure (HF) ranks among the foremost causes of mortality globally, exhibiting particularly high prevalence and significant impact within intensive care units (ICUs). This study sought to develop, validate, and deploy a time-dependent machine learning model aimed at predicting the one-year all-cause mortality risk in ICU patients diagnosed with HF, thereby facilitating precise prognostic evaluation and risk stratification. Methods: This study encompassed a cohort of 8960 ICU patients with HF sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (version 3.1). This latest version of the database added data from 2020 to 2022 on the basis of version 2.2 (covering data from 2008 to 2019); therefore, data spanning 2008 to 2019 (n = 5748) were designated for the training set, while data from 2020 to 2022 (n = 3212) were reserved for the test set. The primary endpoint of interest was one-year all-cause mortality. Least Absolute Shrinkage and Selection Operator (LASSO) regression was employed to select predictive features from an initial pool of 64 candidate variables (including demographic characteristics, vital signs, comorbidities and complications, therapeutic interventions, routine laboratory data, and disease severity scores). Four predictive models were developed and compared: Cox proportional hazards, random survival forest (RSF), Cox proportional hazards deep neural network (DeepSurv), and eXtreme Gradient Boosting (XGBoost). Model performance was assessed using the concordance index (C-index) and Brier score, with model interpretability addressed through SHapley Additive exPlanations (SHAP) and time-dependent Survival SHapley Additive exPlanations (SurvSHAP(t)). Results: This study revealed a one-year mortality rate of 46.1% within the population under investigation. In the training set, LASSO effectively identified 24 features in the model. In the test set, the XGBoost model exhibited superior predictive performance, as evidenced by a C-index of 0.772 and a Brier score of 0.161, outperforming the Cox model (C-index: 0.740, Brier score: 0.175), the RSF model (C-index: 0.747, Brier score: 0.178), and the DeepSur model (C-index: 0.723, Brier score: 0.183). Decision curve analysis validated the clinical utility of the XGBoost model across a broad spectrum of risk thresholds. Feature importance analysis identified the red cell distribution width-to-albumin ratio (RAR), Charlson Comorbidity Index, Simplified Acute Physiology Score II (SAPS II), Acute Physiology Score III (APS III), and the age–bilirubin–INR–creatinine (ABIC) score as the top five predictive factors. Consequently, an online risk prediction tool based on this model has been developed and is publicly accessible. Conclusions: The time-dependent XGBoost model demonstrated robust predictive capability in evaluating the one-year all-cause mortality risk in critically ill HF patients. This model offered a useful tool for early risk identification and supported timely interventions.

Emerging Trends in Glaucoma Management: Advancements in Diagnostic Modalities, Therapeutic Interventions, and Personalized Medicine Approaches

Glaucoma, a progressive optic neuropathy characterized by retinal ganglion cell degeneration and visual field loss, remains a leading cause of irreversible blindness worldwide. Recent advancements in imaging technologies, minimally invasive surgical techniques (MIGS), and neuroprotective therapies have revolutionized the diagnostic and therapeutic landscape of this multifactorial disease. This article explores contemporary trends in glaucoma care, including the integration of artificial intelligence (AI) in optical coherence tomography (OCT) analysis, the role of biomarkers in early detection, and the paradigm shift toward personalized treatment strategies. Additionally, we review novel pharmacological agents targeting intraocular pressure (IOP)-independent mechanisms, such as Rho kinase inhibitors and adenosine receptor agonists, as well as innovations in sustained-release drug delivery systems. The synthesis of current evidence underscores the importance of a multidisciplinary approach to optimize patient outcomes and mitigate disease progression in at-risk populations.