Reducing acetylated tau is neuroprotective in brain injury.

Traumatic brain injury (TBI) is the largest non-genetic, non-aging related risk factor for Alzheimer's disease (AD). We report here that TBI induces tau acetylation (ac-tau) at sites acetylated also in human AD brain. This is mediated by S-nitrosylated-GAPDH, which simultaneously inactivates Sirtuin1 deacetylase and activates p300/CBP acetyltransferase, increasing neuronal ac-tau. Subsequent tau mislocalization causes neurodegeneration and neurobehavioral impairment, and ac-tau accumulates in the blood. Blocking GAPDH S-nitrosylation, inhibiting p300/CBP, or stimulating Sirtuin1 all protect mice from neurodegeneration, neurobehavioral impairment, and blood and brain accumulation of ac-tau after TBI. Ac-tau is thus a therapeutic target and potential blood biomarker of TBI that may represent pathologic convergence between TBI and AD. Increased ac-tau in human AD brain is further augmented in AD patients with history of TBI, and patients receiving the p300/CBP inhibitors salsalate or diflunisal exhibit decreased incidence of AD and clinically diagnosed TBI.

Hepatocellular carcinoma reduced, HBsAg loss increased, and survival improved after finite therapy in hepatitis B patients with cirrhosis.

BACKGROUND AND AIMS: Long-term nucleos(t)ide analog (Nuc) treatment can reduce HCC in patients with HBV-related liver cirrhosis (HBV-LC). Earlier small cohort studies showed a comparable 5-year incidence of HCC in HBeAg-negative patients with HBV-LC who stopped and those continued Nuc therapy. This study aimed to validate these findings using a large cohort with 10-year follow-up. APPROACH AND RESULTS: From 2 centers, 494 HBeAg-negative patients with HBV-LC who stopped (finite group) and 593 who continued (continuous group) Nuc therapy were recruited. HCC, HBsAg loss, liver-related mortality/transplantation, and overall survival rates were compared between 2 groups with 1:1 propensity score matching of sex, treatment history, types of Nuc, age, transaminases, platelet count, and HBsAg levels at end of therapy in finite group or 3-year on-therapy in continuous groups. During a median follow-up of 6.2 (3.4-8.9) years, the annual and 10-year HCC incidence were lower in finite group (1.6 vs. 3.3%/y and 10-y 15.7% vs. 26.8%, respectively; log-rank test, p <0.0001). The finite group showed greater HBsAg decline/year (-0.116 vs. -0.095 log 10 IU/mL, p =0.0026) and 7.6 times higher 10-year incidence of HBsAg loss (22.7% vs. 3%, p <0.0001). Multivariate Cox regression showed finite therapy an independent factor for HBsAg loss (adjusted HR: 11.79) but protective against HCC (adjusted HR: 0.593), liver-related mortality/transplantation (adjusted HR: 0.312), and overall mortality (adjusted HR: 0.382). CONCLUSIONS: Finite Nuc therapy in HBeAg-negative HBV-LC may reduce HCC incidence, increase HBsAg loss, and improve survival. Greater HBsAg decline/loss may reflect enhanced immunity and contribute to the reduction of hepatic carcinogenesis.

Heterogeneity of Islet-Infiltrating IL-21+ CD4 T Cells in a Mouse Model of Type 1 Diabetes.

IL-21 is essential for type 1 diabetes (T1D) development in the NOD mouse model. IL-21-expressing CD4 T cells are present in pancreatic islets where they contribute to T1D progression. However, little is known about their phenotype and differentiation states. To fill this gap, we generated, to our knowledge, a novel IL-21 reporter NOD strain to further characterize IL-21+ CD4 T cells in T1D. IL-21+ CD4 T cells accumulate in pancreatic islets and recognize ß cell Ags. Single-cell RNA sequencing revealed that CD4 T effector cells in islets actively express IL-21 and they are highly diabetogenic despite expressing multiple inhibitory molecules, including PD-1 and LAG3. Islet IL-21+ CD4 T cells segregate into four phenotypically and transcriptionally distinct differentiation states, that is, less differentiated early effectors, T follicular helper (Tfh)-like cells, and two Th1 subsets. Trajectory analysis predicts that early effectors differentiate into both Tfh-like and terminal Th1 cells. We further demonstrated that intrinsic IL-27 signaling controls the differentiation of islet IL-21+ CD4 T cells, contributing to their helper function. Collectively, our study reveals the heterogeneity of islet-infiltrating IL-21+ CD4 T cells and indicates that both Tfh-like and Th1 subsets produce IL-21 throughout their differentiation process, highlighting the important sources of IL-21 in T1D pathogenesis.

Bodipy-based quinoline derivative as a highly Hg2+-selective fluorescent chemosensor and its potential applications.

A highly efficient sensor has been successfully developed using quinoline-based BODIPY compounds (8-quinoline-4,4-difluoro-4-boro-3a, 4a-diazaindacene (C1) and 7-hydroxy-8-quinoline-4,4-difluoro-4-boro-3a, 4a-diazindacene (C2) to detect Hg2+ ions. The sensor C1 exhibits remarkable selectivity in detecting Hg2+ with a limit of detection 3.06 × 10-8 mol/L. The developed chemical sensors have shown stability, cost-effectiveness, ease of preparation, and remarkable selectivity towards Hg2+ ions compared to other commonly occurring metal ions. The total recovery of the sensor C1 can be achieved by using a 0.1 mol/L solution of KI. The proposed sensor C1 has been applied to determine Hg2+ in tap and distilled water, yielding excellent results. In addition, the binding mode of C1-Hg2+ and C2-Hg2+ complexes was a 1:1 ratio confirmed by mass spectra, Job's plot, and DFT study. Moreover, the sensor C1 successfully applied for the biological studies results in negligible cytotoxicity, which demonstrates it can be used to determine Hg2+ in HT22 cells.

Massively Enhanced Charge Selectivity, Ion Transport, and Osmotic Energy Conversion by Antiswelling Nanoconfined Hydrogels.

Developing a nanofluidic membrane with simultaneously enhanced ion selectivity and permeability for high-performance osmotic energy conversion has largely been unexplored. Here, we tackle this issue by the confinement of highly space-charged hydrogels within an orderedly aligned nanochannel array membrane. The nanoconfinement effect endows the hydrogel-based membrane with excellent antiswelling property. Furthermore, experimental and simulation results demonstrate that such a nanoconfined hydrogel membrane exhibits massively enhanced cation selectivity and ion transport properties. Consequently, an amazingly high power density up to ∼52.1 W/m2 with an unprecedented energy conversion efficiency of 37.5% can be reached by mixing simulated salt-lake water (5 M NaCl) and river water (0.01 M NaCl). Both efficiency indexes surpass those of most of the state-of-the-art nanofluidic membranes. This work offers insights into the design of highly ion-selective membranes to achieve ultrafast ion transport and high-performance osmotic energy harvesting.

Cellular Senescence Contributes to the Progression of Hyperoxic Bronchopulmonary Dysplasia.

Oxidative stress, inflammation, and endoplasmic reticulum (ER) stress sequentially occur in bronchopulmonary dysplasia (BPD), and all result in DNA damage. When DNA damage becomes irreparable, tumor suppressors increase, followed by apoptosis or senescence. Although cellular senescence contributes to wound healing, its persistence inhibits growth. Therefore, we hypothesized that cellular senescence contributes to BPD progression. Human autopsy lungs were obtained. Sprague-Dawley rat pups exposed to 95% oxygen between Postnatal Day 1 (P1) and P10 were used as the BPD phenotype. N-acetyl-lysyltyrosylcysteine-amide (KYC), tauroursodeoxycholic acid (TUDCA), and Foxo4 dri were administered intraperitoneally to mitigate myeloperoxidase oxidant generation, ER stress, and cellular senescence, respectively. Lungs were examined by histology, transcriptomics, and immunoblotting. Cellular senescence increased in rat and human BPD lungs, as evidenced by increased oxidative DNA damage, tumor suppressors, GL-13 stain, and inflammatory cytokines with decreased cell proliferation and lamin B expression. Cellular senescence-related transcripts in BPD rat lungs were enriched at P10 and P21. Single-cell RNA sequencing showed increased cellular senescence in several cell types, including type 2 alveolar cells. In addition, Foxo4-p53 binding increased in BPD rat lungs. Daily TUDCA or KYC, administered intraperitoneally, effectively decreased cellular senescence, improved alveolar complexity, and partially maintained the numbers of type 2 alveolar cells. Foxo4 dri administered at P4, P6, P8, and P10 led to outcomes similar to TUDCA and KYC. Our data suggest that cellular senescence plays an essential role in BPD after initial inducement by hyperoxia. Reducing myeloperoxidase toxic oxidant production, ER stress, and attenuating cellular senescence are potential therapeutic strategies for halting BPD progression.

Probing the neural dynamics of musicians' and non-musicians' consonant/dissonant perception: Joint analyses of electrical encephalogram (EEG) and functional magnetic resonance imaging (fMRI).

The perception of two (or more) simultaneous musical notes, depending on their pitch interval(s), could be broadly categorized as consonant or dissonant. Previous literature has suggested that musicians and non-musicians adopt different strategies when discerning music intervals: while musicians rely on the frequency ratios between the two fundamental frequencies, such as "perfect fifth" (3:2) as consonant and "tritone" (45:32) as dissonant intervals; non-musicians may rely on the presence of 'roughness' or 'beats', generated by the difference of fundamental frequencies, as the key elements of 'dissonance'. The separate Event-Related Potential (ERP) differences in N1 and P2 along the midline electrodes provided evidence congruent with such 'separate reliances'. To replicate and to extend, in this study we reran the previous experiment, and separately collected fMRI data of the same protocol (with sparse sampling modifications). The behavioral and EEG results largely corresponded to our previous finding. The fMRI results, with the joint analyses by univariate, psycho-physiological interaction, and representational similarity analysis (RSA) approaches, further reinforce the involvement of central midline-related brain regions, such as ventromedial prefrontal and dorsal anterior cingulate cortex, in consonant/dissonance judgments. The final spatiotemporal searchlight RSA provided convincing evidence that the medial prefrontal cortex, along with the bilateral superior temporal cortex, is the joint locus of midline N1 and dorsal anterior cingulate cortex for the P2 effect (for musicians). Together, these analyses reaffirm that musicians rely more on experience-driven knowledge for consonance/dissonance perception; but also demonstrate the advantages of multiple analyses in constraining the findings from both EEG and fMRI.

PS2MS: A Deep Learning-Based Prediction System for Identifying New Psychoactive Substances Using Mass Spectrometry.

The rapid proliferation of new psychoactive substances (NPS) poses significant challenges to conventional mass-spectrometry-based identification methods due to the absence of reference spectra for these emerging substances. This paper introduces PS2MS, an AI-powered predictive system designed specifically to address the limitations of identifying the emergence of unidentified novel illicit drugs. PS2MS builds a synthetic NPS database by enumerating feasible derivatives of known substances and uses deep learning to generate mass spectra and chemical fingerprints. When the mass spectrum of an analyte does not match any known reference, PS2MS simultaneously examines the chemical fingerprint and mass spectrum against the putative NPS database using integrated metrics to deduce possible identities. Experimental results affirm the effectiveness of PS2MS in identifying cathinone derivatives within real evidence specimens, signifying its potential for practical use in identifying emerging drugs of abuse for researchers and forensic experts.

Multimodal single-cell/nucleus RNA sequencing data analysis uncovers molecular networks between disease-associated microglia and astrocytes with implications for drug repurposing in Alzheimer's disease.

Because disease-associated microglia (DAM) and disease-associated astrocytes (DAA) are involved in the pathophysiology of Alzheimer's disease (AD), we systematically identified molecular networks between DAM and DAA to uncover novel therapeutic targets for AD. Specifically, we develop a network-based methodology that leverages single-cell/nucleus RNA sequencing data from both transgenic mouse models and AD patient brains, as well as drug-target network, metabolite-enzyme associations, the human protein-protein interactome, and large-scale longitudinal patient data. Through this approach, we find both common and unique gene network regulators between DAM (i.e., PAK1, MAPK14, and CSF1R) and DAA (i.e., NFKB1, FOS, and JUN) that are significantly enriched by neuro-inflammatory pathways and well-known genetic variants (i.e., BIN1). We identify shared immune pathways between DAM and DAA, including Th17 cell differentiation and chemokine signaling. Last, integrative metabolite-enzyme network analyses suggest that fatty acids and amino acids may trigger molecular alterations in DAM and DAA. Combining network-based prediction and retrospective case-control observations with 7.2 million individuals, we identify that usage of fluticasone (an approved glucocorticoid receptor agonist) is significantly associated with a reduced incidence of AD (hazard ratio [HR] = 0.86, 95% confidence interval [CI] 0.83-0.89, P < 1.0 × 10-8). Propensity score-stratified cohort studies reveal that usage of mometasone (a stronger glucocorticoid receptor agonist) is significantly associated with a decreased risk of AD (HR = 0.74, 95% CI 0.68-0.81, P < 1.0 × 10-8) compared to fluticasone after adjusting age, gender, and disease comorbidities. In summary, we present a network-based, multimodal methodology for single-cell/nucleus genomics-informed drug discovery and have identified fluticasone and mometasone as potential treatments in AD.

Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study.

BACKGROUND AND AIMS: Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis. METHODS: The discovery phase included 1000 participants from the KORA F4 study, whose plasma protein levels were quantified using the aptamer-based SOMAscan proteomics platform. We evaluated the associations of plasma protein levels with CHD using logistic regression, and with CIMT using linear regression. For both outcomes we applied two models: an age-sex adjusted model, and a model additionally adjusted for body mass index, smoking status, physical activity, diabetes status, hypertension status, low density lipoprotein, high density lipoprotein, and triglyceride levels (fully-adjusted model). The replication phase included a matched case-control sample from the independent KORA F3 study, using ELISA-based measurements of galectin-4. Pathway analysis was performed with nominally associated proteins (p-value < 0.05) from the fully-adjusted model. RESULTS: In the KORA F4 sample, after Bonferroni correction, we found CHD to be associated with five proteins using the age-sex adjusted model: galectin-4 (LGALS4), renin (REN), cathepsin H (CTSH), and coagulation factors X and Xa (F10). The fully-adjusted model yielded only the positive association of galectin-4 (OR = 1.58, 95% CI = 1.30-1.93), which was successfully replicated in the KORA F3 sample (OR = 1.40, 95% CI = 1.09-1.88). For CIMT, we found four proteins to be associated using the age-sex adjusted model namely: cytoplasmic protein NCK1 (NCK1), insulin-like growth factor-binding protein 2 (IGFBP2), growth hormone receptor (GHR), and GDNF family receptor alpha-1 (GFRA1). After assessing the fully-adjusted model, only NCK1 remained significant (ß = 0.017, p-value = 1.39e-06). Upstream regulators of galectin-4 and NCK1 identified from pathway analysis were predicted to be involved in inflammation pathways. CONCLUSIONS: Our proteome-wide association study identified galectin-4 to be associated with CHD and NCK1 to be associated with CIMT. Inflammatory pathways underlying the identified associations highlight the importance of inflammation in the development and progression of CHD.

Enhancing plastic biodegradation process: strategies and opportunities.

Plastic biodegradation has emerged as a sustainable approach and green alternative in handling the ever-increasing accumulation of plastic wastes in the environment. The complete biodegradation of polyethylene terephthalate is one of the most recent breakthroughs in the field of plastic biodegradation. Despite the success, the effective and complete biodegradation of a wide variety of plastics is still far from the practical implementation, and an on-going effort has been mainly devoted to the exploration of novel microorganisms and enzymes for plastic biodegradation. However, alternative strategies which enhance the existing biodegradation process should not be neglected in the continuous advancement of this field. Thus, this review highlights various strategies which have shown to improve the biodegradation of plastics, which include the pretreatment of plastics using UV irradiation, thermal, or chemical treatments to increase the susceptibility of plastics toward microbial action. Alternative pretreatment strategies are also suggested and compared with the existing techniques. Besides, the effects of additives such as pro-oxidants, natural polymers, and surfactants on plastic biodegradation are discussed. In addition, considerations governing the biodegradation performance, such as the formulation of biodegradation medium, cell-free biocatalysis, and physico-chemical properties of plastics, are addressed. Lastly, the challenges and future prospects for the advancement of plastic biodegradation are also highlighted.

The Relationship between Allergic Disease and Sexual Dysfunction: A Scoping Review.

INTRODUCTION: Sexual dysfunction (SD) and allergic disease are common health concerns worldwide and bear a potential relationship. This scoping review is conducted to analyze the currently available data regarding the associations between these two health issues. METHODS: A comprehensive literature search was performed in the databases of PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to retrieve studies that were published before January 2023. A narrative synthesis was conducted to analyze the effects of allergic diseases on SD based on the evaluation of the Female Sexual Function Index (FSFI) and International Index of Erectile Function (IIEF). RESULTS: Twelve observational studies were included after the selection process. The results generally suggested lower FSFI or IIEF scores in patients with asthma, allergic rhinitis, allergic rhinoconjunctivitis, and urticaria compared to the healthy control groups. The underlying factors of this relationship could be inflammation, psychological factors, hormonal changes, sleep disorders, sexual behavior-related allergic reactions, social economic status, and the use of medications. CONCLUSION: SD and allergic disease are interrelated based on the extant literature. This scoping review provides insights into the clinical implications of both entities, while more research studies are warranted to further elucidate this complex relationship.

Endothelin-1 impairs skeletal muscle myogenesis and development via ETB receptors and p38 MAPK signaling pathway.

Myopenia is a condition marked by progressive decline of muscle mass and strength and is associated with aging or obesity. It poses the risk of falling, with potential bone fractures, thereby also increasing the burden on family and society. Skeletal muscle wasting is characterized by a reduced number of myoblasts, impaired muscle regeneration and increased muscle atrophy markers (Atrogin-1, MuRF-1). Endothelin-1 (ET-1) is a potent vasoconstrictor peptide. Increased circulating levels of ET-1 is noted with aging and is associated with muscular fibrosis and decline of strength. However, the regulatory mechanism controlling its effect on myogenesis and atrophy remains unknown. In the present study, the effects of ET-1 on myoblast proliferation, differentiation and development were investigated in C2C12 cells and in ET-1-infused mice. The results show that ET-1, acting via ETB receptors, reduced insulin-stimulated cell proliferation, and also reduced MyoD, MyoG and MyHC expression in the differentiation processes of C2C12 myoblasts. ET-1 inhibited myoblast differentiation through ETB receptors and the p38 mitogen-activated protein kinase (MAPK)-dependent pathway. Additionally, ET-1 decreased MyHC expression in differentiated myotubes. Inhibition of proteasome activity by MG132 ameliorated the ET-1-stimulated protein degradation in differentiated C2C12 myotubes. Furthermore, chronic ET-1 infusion caused skeletal muscle atrophy and impaired exercise performance in mice. In conclusion, ET-1 inhibits insulin-induced cell proliferation, impairs myogenesis and induces muscle atrophy via ETB receptors and the p38 MAPK-dependent pathway.

Surface Modification of Nanopores in an Anodic Aluminum Oxide Membrane through Dopamine-Assisted Codeposition with a Zwitterionic Polymer.

Surface modification through dopamine-assisted codeposition with functional zwitterionic polymers can provide a simple and one-step functionalization under ambient conditions with robust and stable dopamine-surface interactions to improve the hydrophilicity of nanoporous membranes, thereby expanding their applicability to nanofiltration, ion transport, and blood purification. However, a significant knowledge gap remains in our comprehension of the mechanisms underlying the formation and deposition of dopamine/polymer aggregated coatings within nanoscale confinement. This study explores a feasible method for membrane modification through the codeposition of dopamine hydrochloride (DA) and poly(sulfobetaine methacrylate) (PSBMA) on nanopores of anodic aluminum oxide (AAO) membranes. Our findings demonstrate that the aggregated coatings of DA and PSBMA nanocomposites can effectively deposit on the surfaces within cylindrical AAO nanopores, significantly enhancing the hydrophilicity of the nanoporous membranes. The morphology and homogeneity of the nanocomposite coatings within the nanopores are further investigated by varying PSBMA molecular weights and AAO pore sizes, revealing that higher molecular weights result in more uniform deposition. This work sheds light on understanding the codeposition of DA and zwitterionic polymers in nanoscale environments, highlighting a straightforward and stable surface modification process of nanoporous membranes involving functional polymers.

Neuroserpin normalization by mesenchymal stem cell therapy after encephalopathy of prematurity in neonatal rats.

BACKGROUND: Hypoxic-ischemia (HI), infection/inflammation and reperfusion injury are pathogenic factors of encephalopathy of prematurity, which involves maturational/neurotrophic disturbances in oligodendrocyte progenitor cells (OPC) and neurons/axons. Mesenchymal stem cells (MSCs) might facilitate neuroserpin production, which is neurotrophic for OPC/neurons. This study investigated MSC effects on developmental disturbances after lipopolysaccharide (LPS)-sensitized HI/reperfusion (LHIR) injury and the relation to neuroserpin expression. METHODS: Postnatal day 2 (P2) rat pups received intraperitoneal LPS (5 µg/kg) injection followed by HI (unilateral common-carotid-artery ligation and 6.5% oxygen exposure for 90 min) and post-HI reperfusion (release of ligation). MSCs (5 × 104 cells) were injected into the left lateral ventricle at 24 h post-LHIR. Neurological tests and brain tissue examinations were performed between P5 and P56. RESULTS: After LHIR injury, MSC therapy significantly reduced cell death in subplate neurons, attenuated axonal damage, and facilitated synaptophysin synthesis in the cortex. It also alleviated OPC maturation arrest and preserved the complexity of myelinated axons in the white matter, leading to cognitive, motor and behavioral functional improvements. These beneficial effects were linked to restored neuroserpin expression in subplate neurons. CONCLUSIONS: MSC therapy ameliorated developmental disturbances after LHIR injury through protection of neuroserpin expression, serving as a promising approach for treating encephalopathy of prematurity. IMPACT: Neuroserpin is secreted by subplate neurons and may regulate the development of neurons and oligodendrocyte-axon contact for myelination in the premature brain. LPS-sensitized hypoxic-ischemia/reperfusion (LHIR) injury caused the developmental disturbances of neurons/axons and oligodendrocytes, and lowered neuroserpin levels in a neonatal rat model simulating encephalopathy of prematurity. Mesenchymal stem cell therapy alleviated the developmental disturbances after LHIR injury through protection of neuroserpin expression in subplate neurons, offering a new perspective on potential treatment for encephalopathy of prematurity.

High-performance monolayer MoS2nanosheet GAA transistor.

In this article, a 0.7 nm thick monolayer MoS2nanosheet gate-all-around field effect transistors (NS-GAAFETs) with conformal high-κmetal gate deposition are demonstrated. The device with 40 nm channel length exhibits a high on-state current density of ~410µAµm-1with a large on/off ratio of 6 × 108at drain voltage = 1 V. The extracted contact resistance is 0.48 ± 0.1 kΩµm in monolayer MoS2NS-GAAFETs, thereby showing the channel-dominated performance with the channel length scaling from 80 to 40 nm. The successful demonstration of device performance in this work verifies the integration potential of transition metal dichalcogenides for future logic transistor applications.

The association between proton-pump inhibitor use and recurrence of hepatocellular carcinoma after hepatectomy.

BACKGROUND AND AIM: The association between long-term proton-pump inhibitors (PPIs) use and malignancies had long been discussed, but it still lacks consensus. Our study investigated the association between PPI use and hepatocellular carcinoma (HCC) recurrence following curative surgery. METHODS: We retrospectively enrolled 6037 patients with HCC who underwent hepatectomy. Patients were divided into four groups according to their PPI usage. (non-users: < 28 cumulative defined daily dose [cDDD]; short-term users: 28-89 cDDD; mid-term users: 90-179 cDDD, and long-term users: ≥ 180 cDDD, respectively). Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazard models. RESULTS: Among the 6037 HCC patients, 2043 (33.84%) were PPI users. PPI users demonstrated better median RFS (3.10 years, interquartile range [IQR] 1.49-5.01) compared with non-users (2.73 years, IQR 1.20-4.74; with an adjusted hazard ratio [aHR] of 0.57, 95% confidence interval [CI] 0.44-0.74, P < 0.001). When considering the cumulative dosage of PPI, only long-term PPI users had significant lower risk of HCC recurrence than non-PPI group (adj-HR: 0.50; 95% CI: 0.35-0.70; P < 0.001). Moreover, the impact of long-term PPIs use on improving RFS was significant in most of the subgroup analysis, except in patients with advanced tumor stages, with non-cirrhosis, or with a history of chronic kidney disease. However, there were no significant differences in median OS between PPI users and non-users (4.23 years, IQR 2.73-5.86 vs 4.04 years, IQR 2.51-5.82, P = 0.369). CONCLUSION: Long-term PPI use (≥ 180 cDDD) may be associated with a better RFS in HCC patients after hepatectomy.

Electrophysiological differences in inhibitory control processing between collegiate level soccer players and non-athletes in the absence of performance differences.

Inhibitory control, the ability to manage conflicting responses and suppress inappropriate actions, is crucial for team sports athletes, including soccer players. While previous studies have shown that soccer players possess superior inhibitory control, the underlying mechanisms responsible for this advantage remain unclear. Thus, this research aimed to investigate the neural processes involved in conflict resolution and response inhibition, comparing collegiate level soccer players with non-athletes. Participants completed a novel go/no-go task that involved conflict resolution and response inhibition, while their electroencephalograms were recorded. Despite no significant difference in behavioral performance between the two groups, soccer players exhibited notable N2 and frontal midline theta modulations in response to conflict resolution and inhibition, which were comparatively weaker in non-athletes. Our findings suggest that expertise in team sports may enhance neural sensitivity to subtle yet significant information, even without a discernible behavioral advantage.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Prognosticating Prosthetic Ambulation Ability in People With Lower Limb Amputation in Early Post-operative Phase.

OBJECTIVE: To formulate a prognostication model in the early post-operation phase of lower limb amputation to predict patient's ability to ambulate with a prosthesis post rehabilitation. DESIGN: Retrospective cohort study, using data collected from electronic medical records. Predictive factors and prosthetic ambulation outcomes post rehabilitation were used to develop prognostic models via machine learning techniques. SETTING: Regional hospital's ambulatory rehabilitation clinic. PARTICIPANTS: Patients with major lower limb amputation (N=329). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The outcome of prosthetic ambulation ability post rehabilitation collected was categorized in 3 groups: non-ambulant with prosthesis, homebound ambulant with prosthesis (AP), and community AP. RESULTS: In a 2-class model of non-ambulant and AP (homebound and community), the model with highest accuracy of prediction included ethnicity, total Functional Comorbidity Index (FCI), level of amputation, being community ambulant prior to amputation, and age. The f1-score and area under receiver operator curve (AUROC) of the model is 0.78 and 0.82. In a 3-class model consisting of all 3 groups of outcomes, the model with highest accuracy of prediction required 10 factors. The additional factors from the 2-class model include presence of caregiver, history of congestive heart failure, diabetes, visual impairment, and stroke. The 3-class model has a moderate accuracy with a f1-score and AUROC of 0.60 and 0.79. CONCLUSION: The 2-class prognostication model has a high accuracy which can be used early post-amputation to predict if patient would be ambulant with a prosthesis post rehabilitation. The 3-class prognostication model has moderate accuracy and is able to further differentiate the walking ability to either homebound or community ambulation with a prosthesis, which can assist in prosthetic prescription and setting realistic rehabilitation goals.