Addiction is a chronic, relapsing neuropsychiatric disorder despite adverse consequences. Addiction involves neurobiological changes in the reward, motivation, and memory systems, particularly affecting the dopaminergic pathways due to a complex interaction between inherited traits and life experiences. To explore the role of genes in addictive behavior, we compiled a list of 332 clinically relevant genes from literature sources and searched GeneAnalytics, STRING web-based programs, and integrated genetic and protein databases for interactions and molecular profiles of genes in tissues and cells, diseases, pathways, biological processes, cellular components, functions, phenotypes, and compounds. We identified 332 genes associated with addictive behavior and predominantly expressed in the brain associated with schizophrenia, nervous system disorders, and cancer. Nine of the top 10 related pathways showed GPCR protein interaction and signaling involving the CREB1, MAPK1, MAPK3, and AKT1 genes. The BDNF gene was recognized in eight of the top 10 high-scoring phenotypes involving the neurotransmitters dopamine and glutamate. We chose to study AKT1 as the most identified gene when searching web-based programs and integrated genetic and protein databases. This gene encodes protein kinases that are required for protein phosphorylation, fundamental for most cellular functions, stabilization, regulation of targeted proteins including cell cycle control and signal transduction, neuron formation, and neurological function including the hippocampus. We identified the important PI3/AKT/mTOR signaling pathway that integrates extracellular growth signals, promotes proliferation, and inhibits apoptosis, which is important for brain function. These genes also overlap with other genes associated with ATPase activity, metabolism, and chaperone protein functions that play a role in addiction. In addition, we identified 29 genes that are shared with alcoholism/alcohol use disorder and overlap with interactive molecular functions and processes between alcoholism and addiction. Our study identified 332 addiction genes from literature sources and used in silico integrated genetic approaches with two searchable web-based programs to provide insights into the complex molecular and genetic architecture of addiction. We identified cell cycle control factors, extracellular growth, signal transduction, and metabolism. The pathways involved selective protein phosphorylation and transduction of proteins as well as neurotrophic factors with mechanisms impacting nervous system development, plasticity and function when disturbed, leading to addictive behavior. Several genes associated with addiction overlapped with those associated with alcohol use disorder.
Climate change disproportionately affects poorer countries like Uganda, intensifying poverty and livelihood stress, which can escalate gender-based violence (GBV). Although the parent study was not designed to focus on GBV, GBV emerged repeatedly during interviews and focus groups; this paper presents a GBV-focused thematic analysis of those narratives. Particularly, we examine how GBV interconnects with poverty, shifting gender roles, alcoholism, environmental stress, and family planning dynamics. Between April and July 2021, we conducted an exploratory qualitative research study that comprised 28 focus group discussions (FGDs), comprising six-eight participants each, stratified by sex and age (18-25, 25-49, and mixed 50 + groups). Additionally, 40 key informant interviews (KIIs) were held in Rukiga district, Uganda. Purposive sampling was applied. Data were organised in NVivo 12 and analysed thematically. Participants perceived GBV, including intimate partner violence, non-partner sexual violence, child abuse, and early marriage, as widespread and normalised. Two main interconnected driver clusters emerged. First, poverty, male alcohol use, and shifting gender norms contributed to household instability. As men abandoned provider roles, women assumed more responsibilities, provoking conflict and sometimes violence from disempowered male partners. Second, environmental degradation and climate-related stressors (droughts, floods, soil erosion) worsened economic hardship, tensions, and GBV. Population growth and limited land access further strained livelihoods. While family planning was generally supported, male opposition sometimes triggered conflict. Climate change impacts are gendered, with GBV pathways shaped by shifting gender roles, norms, and relations destabilised by environmental and livelihood pressures. Addressing GBV in climate-affected communities requires gender-transformative environmental and livelihood programmes. This should include strengthened social and structural resilience to challenge inequitable gender norms and power imbalances.
Current criteria from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) for clinical diagnosis are not based on evidence. We developed a machine-learning model for the clinical diagnosis of AH. 467 subjects with alcohol associated liver disease (ALD) across seven centers were randomly assigned to training or testing cohorts. Three machine learning algorithms: Random Forest, Gradient Boosting Machine, and XGBoost were derived on the training cohort to identify clinical characteristics associated with histologic AH. Combined Alcohol Hepatitis Ensemble Algorithm Development (AHEAD) model integrating AST, ALT, total serum bilirubin was superior to NIAAA criteria to predict histologic AH in test cohort AUC of 0.695 (0.608-0.782) vs. 0.590 (95% CI 0.494-0.685) (Bootstrap p = 0.049). Using 50% probability cutoff, AHEAD model was 61.5% specific (107 of 174 non-cases correctly identified) and 63.3% sensitive (19 of 30 cases correctly identified) for AH diagnosis. NIAAA model was 54.6% specific (95 of 174 non-cases correctly identified) and 63.3% sensitive (19 of 30 cases correctly identified). The AHEAD model (https://aihepatology.shinyapps.io/AHEAD/) is more specific than the widely utilized NIAAA criteria for clinical diagnosis of AH. It may be useful in clinical trials by reducing enrolment of subjects without AH.
Noneconomic damage caps, a form of medical malpractice law, remain controversial, as several states have enacted such laws since 2010, whereas others have repealed them. The clinical consequences of repealing these caps are poorly understood, and understanding these associations can inform the ongoing debate about medical malpractice reform. To examine whether repealing noneconomic damage caps is associated with changes in maternal care and infant health outcomes. This cross-sectional study adopted a difference-in-differences design, comparing between 2 treated states (Georgia and Illinois) that repealed their noneconomic damage caps in 2008 to 2009 and 16 control states that retained their caps during the entire study period between 2005 and 2019. The Centers for Disease Control and Prevention All-County Natality Files were used to estimate multivariate linear models, controlling for maternal and infant characteristics and county-level and state-level covariates. Estimates were stratified by county rurality and birth risk conditions. Data were analyzed from April 1, 2024, to April 9, 2026. The primary outcomes were 4 measures of maternal care and procedures (physician-attended births, inductions, cesarean delivery births, and prenatal visits) and 3 birth outcomes (low Apgar score, low birth weight, and preterm births). Difference-in-differences models with 2-way fixed effects were estimated, and linear models for the study outcomes were specified. The sample included 20 426 267 live births (mean [SD] gestational age, 38.55 [1.35] weeks). Compared with their counterparts in the control states, rural counties in the treated states experienced a statistically significant increase of 2.92 percentage points (pp) (95% CI, 1.40-4.50 pp; Bonferroni-adjusted P = .01) in physician-attended births. The increase held for both low-risk (3.10 pp; 95% CI, 1.33-4.90 pp; P = .004) and high-risk (2.56 pp; 95% CI, 0.77-4.34 pp; P = .01) births in rural counties. There was no difference between treated and control states for physician-attended births overall or in urban counties. No statistically significant associations were observed for cesarean deliveries, inductions, prenatal visits, or infant health outcomes after adjusting for multiple comparisons. In this cross-sectional study of 20 426 267 live births across 18 states, repealing noneconomic damage caps was associated with increased physician-attended births in rural counties but was not associated with statistically significant changes in other maternal care measures or infant health outcomes. These findings suggest that increased liability risk after repealing the caps may shift the composition of birth attendants in resource-constrained settings without demonstrable changes in infant health.
To develop and test a nomogram model based on drinking patterns and computed tomography and magnetic resonance imaging (CT/MRI) characteristics for recurrence of acute alcoholic pancreatitis (AAP) following its first onset. Patients with initial AAP at the Affiliated Hospital of North Sichuan Medical College were retrospectively enrolled and categorized them into recurrence and non-recurrence groups. They were randomly assigned in a 7:3 ratio to form training and independent test sets, and their clinical and imaging data were collected and analyzed. Nomogram models were established to predict the recurrence of AAP. Among 152 cases of initial AAP, 37 cases were recurrent and 115 were non-recurrent, with a mean (SD) age of 43.84 ± 10.28 years and 91.45% male participants. In the training set, 26 cases were recurrent and 80 were non-recurrent; in the independent test set, 11 cases were recurrent and 35 were non-recurrent. Multivariable logistic regression analysis showed that hyperlipidemia, pre-onset alcohol consumption, alcohol cessation, the Bedside Index for Severity in AP (BISAP) score, extrapancreatic inflammation on CT/MRI (EPIC/EPIM) score, and CT/MRI severity index (CTSI/MRSI) score were independent predictors of recurrence after initial AAP onset. Integrating these factors into a nomogram prediction model resulted in the area under the curve (AUC), sensitivity, and specificity values of 0.924 (95% CI 0.871-0.977), 0.885, and 0.838 for the training set and 0.843 (95% CI 0.714-0.972), 0.727, and 0.857 for the independent test set. The clinical model alone and the imaging model achieved AUCs of 0.799 (95% CI 0.703-0.896) and 0.827 (95% CI 0.742-0.912) in the training set and 0.800 (95% CI 0.646-0.954) and 0.686 (95% CI 0.492-0.880) in the independent test set, respectively. Nomogram models based on drinking patterns and CT/MRI characteristics can more accurately predict AAP recurrence. The model serves as an effective tool for clinical prediction of AAP and helps clinicians in developing personalized prevention and treatment strategies.
Sarcopenia is associated with increased mortality and poor clinical outcomes in patients with liver cirrhosis. However, the correlation between sarcopenia and recompensation has not been determined until now. In this study, we aimed to evaluate the performance of sarcopenia in predicting recompensation in patients with decompensated cirrhosis. A total of 258 patients with decompensated cirrhosis were enrolled in this retrospective study, and the data of enrolled patients were collected and analyzed. 36.82% of patients with decompensated cirrhosis achieved recompensation. The etiology of liver cirrhosis in these patients included HBV, HCV, alcoholic liver disease, autoimmune liver diseases, schistosomiasis infection, and nonalcoholic fatty liver disease. The decompensating events in these patients included ascites (43.02%), esophagogastric variceal bleeding (42.25%), hepatic encephalopathy (5.23%), etc. 27.06% of decompensated patients with sarcopenia and 41.62% of patients without sarcopenia achieved recompensation. Univariate logistic analysis demonstrated several variables were associated with recompensation, including erythrocyte, hemoglobin, L3 skeletal muscle index (SMI), sarcopenia and subcutaneous fat area (SFA) (all p<0.05). Multivariate analysis demonstrated sarcopenia (OR=0.52; p=0.03) and hemoglobin (OR=1.02; p<0.01) were independent predictors for recompensation. Sarcopenia and hemoglobin were independent predictors for recompensation of decompensated patients, which helped to identify high-risk patients who have difficulty in achieving recompensation.
Lonicera caerulea is a commercial fruit crop. A polysaccharide (LCP) was extracted from its fruits and characterized as a pyranose polysaccharide with a molecular weight of 4.096 × 105 Da. Monosaccharide composition analysis revealed that LCP was a heteropolysaccharide composed of glucose, mannose, xylose, glucuronic acid, galacturonic acid, rhamnose, and galactose. In a mouse model of acute alcoholic liver injury, oral administration of LCP for 14 days was associated with dose-dependent improvements in serum transaminases, lipid accumulation, oxidative stress markers, and pro-inflammatory cytokines. Histopathological examination confirmed that LCP attenuated alcohol-induced hepatic steatosis and inflammatory infiltration. To explore potential mechanisms, 16S rRNA and ITS-1 sequencing of cecal contents were performed. LCP treatment was associated with increased relative abundance of the bacterial phylum Bacteroidetes and the fungal genus Kazachstania, and decreased relative abundance of the bacterial genus Dubosiella and the fungal genus Mortierella. Correlation analyses revealed that the bacterial and fungal taxa enriched by LCP were negatively correlated with liver injury markers. These findings suggest that LCP may alleviate alcoholic liver disease in association with modulation of the gut bacteriome and mycobiome, providing experimental evidence for the involvement of cross-kingdom microbial interactions in this process.
Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths. Nevertheless, it is estimated that more than 5.7 million people globally are currently living with it. CRC development is influenced by various environmental factors, and the benefits of a healthy lifestyle, particularly dietary changes, are receiving growing attention. While the mechanisms linking specific nutrients to CRC carcinogenesis are still under investigation, evidence suggests that prognosis and long-term outcomes may be influenced by post-diagnosis dietary habits. Here we report data from the ECHO 2.0 study (Eating habits CHanges in Oncologic patients), an observational investigation focused on post-diagnosis dietary changes, among Italian CRC patients. Data were collected from 98 subjects through a questionnaire designed to investigate changes in their food consumption, supplement use, and adoption of specific diets following surgery. Ninety-eight patients (45 females and 53 males) completed the survey, with most aged 65 years or older. We observed that some patients reported positive dietary changes, including an increase in the consumption of vegetables, fresh fruit, and fish and shellfish, as well as a decrease in the intake of processed meat, desserts, red meat, animal fats, alcoholic beverages, refined bread and pasta, soft drinks, and baked goods. Despite CRC survivors made some positive changes to their nutritional habits, those modifications were mostly followed by a few of them, while over half of patients consumed nutritional supplements after diagnosis. Moreover, changes in nutritional habits were mainly adopted without consulting or informing the oncologist, and even if nearly half of patients believed that a moderate or strong link existed between cancer and nutrition, only one-third of them sought dietary information after being diagnosed. Our findings suggest that, after diagnosis, CRC patients have made modest dietary changes, with only a few increasing their consumption of healthy foods. Furthermore, a significant proportion of survivors did not seek dietary information after their diagnosis, highlighting a gap in patient empowerment. These results emphasize the important role of healthcare providers, particularly oncologists, in identifying diet as a potential risk factor and directing patients toward appropriate nutritional support.
Aims: To examine the level of vendor compliance with age-verification legislation governing alcohol sales in Cyprus across two repeated cross-sectional mystery shopping studies conducted in 2015 and 2024, and to identify factors influencing the likelihood of selling alcoholic beverages to underage-appearing individuals. Methods: In 2015, 200 purchase attempts were conducted across six venue types using paired student mystery shoppers. In 2024, 200 visits were conducted by individual mystery shoppers in comparable venue types, excluding nightclubs. In both studies, vendor responses were coded as: no age verification, verbal confirmation, or ID request. Descriptive statistics were computed, and logistic regression assessed venue and seller characteristics associated with vendor compliance. Results: In 2015, 94.5% of vendors sold alcohol without any verification, verbal confirmation was requested in 4.0%, and only 1.5% requested ID. Logistic regression showed that age verification was more likely with male buyers. In 2024, non-compliance remained high (85.5%), with verbal confirmation requested in 13.5% of visits, and ID requests at just 1%. Regression analyses showed higher compliance in bars than in kiosks, and female mystery shoppers were more often asked for age confirmation. Few vendors reported receiving training or legislative updates, with 22% recalling any regulatory updates and just 15% stating they had ever been formally informed about alcohol sales regulations. Compliance rates remain well below those reported in Northern and Western Europe, where structured inspection and vendor training are routine. Conclusions; Vendor compliance with age-verification laws in Cyprus remains persistently low. The findings highlight the need for systematic compliance monitoring, vendor education, and stronger enforcement policies, contributing to the broader European discussion on effective alcohol-control implementation.
Honey bees face threats from a variety of pathogens and viruses, the most dangerous of which is the deformed wing virus [DWV]. Using natural materials as treatments or nutritional supplements for bees is the ideal solution, especially when transformed into nanoparticles. Propolis is a resinous product collected from honeybee colonies and is known for its wide-ranging therapeutic properties. The nanocomposite of the chitosan/ propolis alcoholic extracts were prepared and characterized for determining their chemical and physical properties. Cytotoxicity assay and antiviral activity of the prepared composites were also determined using cell culture from the head of adult honey bees in a dose-response assay. A quantitative real time-polymerase chain reaction [RT-qPCR] was done to measure their effects on the deformed wing virus load. The characterization results showed that the Caucasian propolis-chitosan nanocomposite have a higher phenols and flavonoid content and surface area compared to the Egyptian propolis. The Caucasian propolis showed higher toxicity to the cultured cells than the Egyptian propolis. The Chitosan-Caucasian propolis nanocomposites caused a more reduction in the deformed wing viral load of the honey bee cell line than the Egyptian one compared to the raw propolis. It is recommended to use the chitosan-Caucasian propolis nanocomposite as therapeutic and nutritional supplements for decreasing the deformed wing viral load in the honey bees a process that may help in increasing their performance and bee-product production.
Forty percent of people with bipolar disorder (BD) develop alcohol use disorder (AUD), with co-occurring AUD substantially worsening the course of BD. Though efficacious treatments remain elusive, frontal glutamate and GABA dysregulation represent promising targets for intervention. This study evaluated the ability of two adjunctive medications, N-acetylcysteine (NAC) and gabapentin, to modulate glutamate and GABA (primary) and to reduce heavy drinking and depressive symptoms (exploratory) in people with BD + AUD. Fifty-four individuals meeting DSM-5 criteria for BD + AUD were enrolled in a randomized, double-blind, placebo-controlled, crossover study, with 3, 1-week conditions (NAC, gabapentin, placebo). Medication effects on dorsal anterior cingulate cortex (dACC) glutamate+glutamine (Glx) and GABA levels, via proton MR spectroscopy, and percent heavy drinking days (%HDD) and depressive symptoms were evaluated with linear mixed models. Forty-nine participants (M[SD] age=41.0[12.2], 51% female, 74% white) provided 121-131 posttreatment-MRI scans, depending on analysis. Medications were well-tolerated, and adherence was excellent. DACC Glx (F = 4.76, p = 0.012) but not GABA (F = 0.96, p = 0.388) levels significantly differed across conditions, with only NAC (M[SD] = 21.50[2.55]) demonstrating significantly different(lower) glutamate levels relative to placebo (M[SD] = 22.59[2.56]; p = 0.003; SMD = 0.43). %HDD (F = 3.90, p = 0.025) also significantly differed across conditions, again with only NAC (M[SD] = 31.86[4.60]) demonstrating significantly different(lower) %HDD relative to placebo (M[SD] = 40.94[4.55]; p = 0.015; SMD = 0.33), though neither NAC (p = 0.128) nor gabapentin (p = 0.228) differed from placebo on depressive symptoms. These results support the development of mechanistic clinical trials targeting glutamatergic dysfunction in people with BD + AUD. Trial Registration: https://clinicaltrials.gov/study/NCT03220776.
Non-alcoholic fatty liver disease (NAFLD) is strongly linked to systemic low-grade inflammation and adverse dietary exposures. Hematologic indices derived from routine blood counts have emerged as accessible indicators of inflammatory and metabolic imbalance. The white blood cell-to-platelet (WBC/PLT) ratio may reflect immune activation in the context of metabolic liver disease; however, data regarding its association with dietary composition and cardiometabolic markers remain limited. This study aimed to examine whether the WBC/PLT ratio is associated with lipid disturbances and dietary components in adults diagnosed with NAFLD. In a cross-sectional analysis of 256 individuals with NAFLD attending a tertiary referral center, participants were stratified into tertiles according to WBC/PLT values. Anthropometric measurements, biochemical profiles, and complete blood counts were obtained using standardized procedures. Habitual dietary intake was evaluated through a validated food frequency questionnaire. Intergroup comparisons were performed using one-way ANOVA, and generalized linear models were applied to adjust for potential confounders including age, sex, body mass index, total energy intake, smoking status, and physical activity. General demographic and anthropometric variables did not differ significantly across tertiles. However, participants in the highest WBC/PLT tertile exhibited significantly elevated triglyceride (TG) concentrations and reduced high density lipoprotein cholesterol (HDL-C) levels after multivariable adjustment. Higher WBC/PLT values were also associated with lower consumption of vitamins C and E. A progressive rise in leukocyte count accompanied by a decline in platelet count was observed across increasing tertiles (P < 0.001 for both). An elevated WBC/PLT ratio is linked to an unfavorable lipid profile and suboptimal dietary components characterized by low antioxidant intake in individuals with NAFLD. These findings suggest that WBC/PLT may serve as a simple, non-invasive indicator of inflammation-related metabolic risk, potentially influenced by dietary quality.
Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder linked to increased risk of type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). The Non-HDL-to-HDL Cholesterol Ratio (NHHR) is an emerging lipid marker, but its predictive value for T2DM and CHD in NAFLD patients is unclear. This study evaluated the association between NHHR and the incidence of T2DM and CHD in a large NAFLD cohort. We conducted a retrospective cohort study involving 13,741 NAFLD patients from the Affiliated Hospital of Guangdong Medical University (2018-2025) and validated our findings in NHANES cohort (1999-2018) comprising 5,789 individuals. Participants were stratified into quartiles, and multivariate logistic regression with restricted cubic splines assessed associations with incident T2DM and CHD, adjusting for confounders. Subgroup, interaction, and mediation analyses elucidated potential effect modifiers and mediators. Higher NHHR was independently associated with an increased risk of T2DM in both cohorts (per unit increase: OR 1.08, 95% CI 1.06-1.11). A nonlinear dose-response relationship was observed, with a marked rise in T2DM risk at higher NHHR levels, and participants in the highest NHHR quartile had 67% higher odds of T2DM compared with the lowest quartile. Mediation analysis indicated that fasting glucose accounted for over half of the NHHR-T2DM association. In contrast, the association between NHHR and CHD was weaker and less consistent across cohorts, suggesting heterogeneity in its cardiovascular predictive value among patients with NAFLD. Findings for T2DM were robust across major subgroups and externally validated in NHANES. NHHR is a simple, readily available lipid index that independently predicts incident T2DM in patients with NAFLD. Its nonlinear risk pattern and partial mediation through glucose metabolism underscore its clinical utility for early risk stratification and personalized prevention strategies.
Dietary composition significantly influences metabolic health, particularly lipid metabolism and liver function. This study aimed to examine the associations between ketogenic, low-fat, and balanced dietary patterns with lipid parameters, liver enzymes, and renal function in the Chinese adult population. This retrospective cross-sectional study analyzed data from 650 adults categorized into 3 dietary groups based on recorded dietary intake: ketogenic (n = 210), low-fat (n = 220), and balanced (n = 220). Demographic, socioeconomic, anthropometric, clinical, and biochemical variables were assessed. Group comparisons were performed using a one-way analysis of variance (ANOVA) and chi-square tests, while a multivariable linear regression analysis was used to evaluate associations between dietary patterns and metabolic outcomes. Baseline demographic and socioeconomic characteristics were comparable across the groups. The ketogenic diet was associated with higher levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with the low-fat and balanced diets (p < 0.01). Higher alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were also observed in association with the ketogenic diet. In adjusted analyses, the ketogenic diet remained significantly associated with increases in total cholesterol (β = +62.9 mg/dL), triglycerides (β = +36.5 mg/dL), LDL-C (β = +34.2 mg/dL), HDL-C (β = +5.6 mg/dL), ALT (β = +8.7 U/L), and AST (β = +5.9 U/L) (all p ≤ 0.001). No significant associations were observed between dietary patterns and renal function markers, including serum creatinine and estimated glomerular filtration rate (eGFR). The ketogenic diet was associated with higher HDL-C and increased atherogenic lipids and liver enzymes; however, no significant association was observed with renal function. These findings highlight the importance of individualized dietary guidance and metabolic monitoring.
In recent decades, death rates from suicides, drug poisonings, and alcoholic liver disease have dramatically increased in the United States. We show that these "deaths of despair" began to increase relative to the trend in the early 1990s, that this increase was preceded by a decline in religious participation, and that both trends were driven by middle-aged white Americans. Using repeals of blue laws, we find that a shock to religious participation has significant effects on these mortality rates. Our findings show that social factors such as organized religion can play an important role in understanding deaths of despair.
Alcoholic hepatitis (AH) is an acute form of alcohol-associated liver disease with very few treatment options. Recent studies highlighted liver metabolic reprogramming in AH as an indicator of severity. We aim at identifying new intervention points to reverse liver metabolic dysregulation across varying degrees of AH. We develop 89 personalized genome-scale metabolic models by integrating a generic human cellular metabolic model with liver transcriptomics data from AH patients with varying disease severity and healthy controls. We grade the AH patients based on the model-predicted level of glycolysis reprogramming and validate the results using published metabolomics data. We test in silico gene knockdown interventions to reverse the aberrant metabolic reprogramming in AH. Knockdown of two glycolytic genes, Hkdc1 and Pkm, significantly rebalance the metabolic fluxes toward a healthy liver metabolic phenotype. We use machine learning on the glycolysis fluxes to develop a quantitative glucose use reprogramming score, which correlates with AH severity and patient-specific responses to in silico gene knockdown interventions. The score was independently validated using a published AH liver transcriptomics dataset. We propose a cellular metabolism-based therapy targeting Hkdc1 and Pkm in the glycolysis pathway as a potential treatment for reversing the aberrant glucose metabolism in AH.
Hepatic pseudolymphoma (HPL) is a rare benign lymphoproliferative disorder that can mimic malignant hepatic tumors on imaging. Hepatic pseudolymphoma is usually small and solitary; however, multiple lesions can develop in some cases. Herein, we report multiple HPLs with an unusual hepatobiliary finding on gadoxetic acid-enhanced MRI. A woman in her 50 s with non-alcoholic fatty liver disease was incidentally found to have 2 hepatic tumors: a 3-cm lesion in segment 5 (S5) and a 1-cm lesion in segment 8 (S8) during pre-operative cholelithiasis evaluation. The laboratory tests, including liver function and tumor marker levels, were unremarkable. The 2 lesions were hyperintense on fat-suppressed T2-weighted images and showed restricted diffusion. On dynamic gadoxetic acid-enhanced MRI, both lesions demonstrated faint arterial enhancement and hepatobiliary-phase hypointensity, with peritumoral arterial-phase hyperenhancement. Additionally, the S5 lesion showed faint linear hyperintensity adjacent to the lesion on diffusion-weighted imaging and contained an internal ring-like area that was hypointense on T2-weighted images but hyperintense within an otherwise hypointense lesion in the hepatobiliary phase. As malignancy could not be excluded, laparoscopic anterior sectionectomy was performed. Histopathological examination confirmed reactive lymphoid hyperplasia in both lesions. In the S5 lesion, the intratumoral fibrotic tissues formed a ring-like structure corresponding to the hepatobiliary-phase hyperintensity. Hepatobiliary-phase ring-like hyperintensity attributable to intratumoral fibrosis in HPL has not been previously reported. Awareness of this imaging-pathology correlation may improve interpretation of HPL imaging and help differentiate it from malignant hepatic tumors that can show hepatobiliary-phase hyperintensity, including hepatocellular carcinoma, cholangiocarcinoma, and metastases.
Recent advances in spectroscopic techniques have provided molecular insights into the supramolecular structures of ethanol-water clusters (EWC) in alcoholic beverages. Sensory quality of these beverages is not only governed by trace flavor compounds but is fundamentally influenced by the dynamic, hydrogen-bonded networks formed between ethanol and water molecules. This review summarizes progress in elucidating the structural characteristics, stability, and transformation mechanisms of EWC across different alcoholic matrices, with a particular emphasis on contributions from multiscale spectroscopic methods including infrared (IR), Raman, nuclear magnetic resonance (NMR), and fluorescence spectroscopy, often coupled with two-dimensional correlation analysis. We further examine how external factors (temperature, electric fields) and endogenous components (acids, esters) modulate EWC architecture and, consequently, perceived taste and mouthfeel. By integrating spectroscopy with computational modeling and artificial intelligence, a more predictive understanding of EWC behavior is emerging, offering a robust scientific foundation for real-time quality monitoring, process optimization, and tailored sensory design in the beverage industry.
The role of dipeptidyl peptidase-4 (DPP-4/CD26) in chronic liver disease (CLD) remains incompletely understood, particularly its interaction with immune cells. This study investigates the association between DPP-4 gene expression and T-cell subset marker genes in CLD patients, aiming to elucidate potential immunological mechanisms underlying disease progression. A total of 130 individuals were enrolled across four groups: non-alcoholic fatty liver disease (NAFLD; n = 46), non-alcoholic cirrhosis (NAC; n = 23), alcoholic cirrhosis (ALC; n = 21), and healthy controls (n = 40). Peripheral blood samples were analysed for biochemical parameters and DPP-4 activity. Gene expression profiling was conducted in peripheral blood mononuclear cells to assess DPP-4 and T-cell marker genes (TBX21, RORC, GATA3, FOXP3, and CD3D). DPP-4 expression was elevated in all CLD subgroups, reaching statistical significance in NAFLD (P = 0.0142). The Th1 marker TBX21 showed increased expression, significantly in NAC (P = 0.0091), and demonstrated a strong correlation with DPP-4 in non-alcoholic CLD. The Th17 marker RORC was significantly elevated in NAFLD (P = 0.016), whereas the Th2 marker GATA3 and the Treg marker FOXP3 were significantly reduced (P = 0.0049 and P = 0.0028, respectively), with FOXP3 showing a negative correlation with DPP-4 (r = 0.588). CD3D expression correlated with DPP-4 in ALC patients. These findings suggest disrupted regulatory coordination rather than uniform Treg suppression across CLD subgroups. NAFLD exhibited partial Th17 polarisation, whereas NAC may reflect Th17 exhaustion. DPP-4 appears to be associated with Th1 responses and may contribute to liver injury in NAC.
Background Adults with neurodevelopmental disorders (NDD) may exhibit a distinct metabolic and nutritional risk profile compared to the general population. Although pediatric studies have reported higher obesity rates in certain neurodevelopmental disorder subtypes, particularly autism spectrum disorder, findings are heterogeneous, and national-level data in adults remain limited. This study assessed the association between NDD and three key metabolic outcomes in hospitalized adults: obesity, non-alcoholic fatty liver disease (NAFLD), and protein-calorie malnutrition. Methods This retrospective study utilized the National Inpatient Sample (2016-2020) and included adults aged 18 years and older. NDD was identified using diagnostic codes for autism spectrum disorder, intellectual disability, and related developmental disorders. The primary outcomes were obesity, NAFLD, and protein-calorie malnutrition. All hospitalizations involving NDD were included. To ensure an adequate pool of potential controls for matching, a 20:1 random sample of non-NDD hospitalizations was initially selected, followed by 1:4 nearest-neighbor propensity score matching based on age, sex, race, primary payer, and income quartile. Survey-weighted multivariable logistic regression models were used to estimate adjusted odds ratios (aORs). Results The final matched cohort comprised 856,315 weighted hospitalizations, including 171,263 adults with NDD and 685,052 matched controls. Propensity score matching achieved excellent covariate balance, with all standardized mean differences <0.10, indicating clinically similar baseline characteristics between groups. Adults with NDD demonstrated an inverse metabolic profile, with lower odds of obesity (aOR 0.76) and NAFLD (aOR 0.56), but higher odds of protein-calorie malnutrition (aOR 1.25).  Conclusions Hospitalized adults with neurodevelopmental disorders exhibit an inverse metabolic profile, characterized by lower odds of obesity and NAFLD but higher odds of malnutrition. These findings contrast with the pediatric literature and indicate that metabolic risk patterns in NDD may shift with age. Recognition of this distinct profile may inform targeted metabolic screening and nutritional interventions for this vulnerable population.