Salvage lung resection after immunotherapy is feasible and safe.

Objectives: Patients with non-small cell lung cancer treated with immunotherapy and modern chemoradiation regimens show improved progression-free and overall survival. However, patients with limited oligo-progression represent a potential population in which local therapy such as surgery may have a potential role as salvage treatment. The objectives of our study were to evaluate the feasibility and safety of salvage lung resection after immunotherapy in patients with non-small cell lung cancer. Methods: The National Cancer Database was queried for patients diagnosed and treated for non-small cell lung cancer stage I to IV, from 2013 to 2020. Patients who underwent surgery as salvage after immunotherapy were defined as undergoing surgery >5 months from the initiation of immunotherapy. As a sensitivity analysis, patients who underwent surgery as salvage after chemoradiation were also analyzed in a similar fashion. Surgical outcomes such as type of surgery, complete resection (R0) rates, and complete pathologic response rates were determined for feasibility. Length of stay, 30-day readmission rates, and 30-day mortality rates were determined and overall survivals were estimated with Kaplan-Meier analysis to evaluate for safety. Results: Of the 934,093 patients diagnosed with non-small cell lung cancer stage I to IV from 2013 to 2020, 164 patients received immunotherapy and after 5 months underwent surgery. Lobectomy was the most commonly performed operation (74%) and pneumonectomy was required in 9% (n = 15). R0 resection was achieved in 89% (n = 146) and of these patients, 23% (n = 37) had complete pathologic response. Median length of stay was 4 days, 30-day readmission was 5%, and 30-day mortality was 0.6%. In our sensitivity analysis of chemoradiation patients (n = 445), the above data were similar to previously reported cohort studies of patients undergoing chemoradiation and subsequently salvage surgery. Conclusions: Lung resection after immunotherapy appears to be a feasible salvage treatment option, with lobectomy being most common and with high R0 resection rates. Low patient morbidity and mortality rates also suggest the safety of this approach. Salvage surgery may be considered in patients who have oligo-progression after immunotherapy within the context of a comprehensive multidisciplinary treatment plan.

A pilot pharmacokinetic and Metabolite identification study of Erinacine A in a Single landrace pig model.

Erinacine A has been proven to have the ability to protect nerves and have the benefit of neurohealth. However, the pharmacokinetic and metabolites study of erinacine A in pigs, whose physiology and anatomy are similar to humans, have not been reported. In this study, 5 mg/kg of erinacine A was intravenously administered to the landrace pig. Blood, cerebrospinal fluid, and brain tissue samples were collected and analyzed by HPLC-QQQ/MS and UPLC-QTOF/MS. The results indicated the following pharmacokinetic parameters in plasma samples: with an area under the plasma concentration versus time curve (AUC) were 38.02 ± 0.03 mg∙min/L (AUC0-60) and 43.60 ± 0.06 mg∙min/L (AUC0-∞), clearance (CL) was 0.11 ± 0.00 L/min∙kg, volume of distribution (Vd) was 4.24 ± 0.00 L/kg, and terminal half-life (T1/2ß) was 20.85 ± 0.03 min. In the cerebrospinal fluid samples, erinacine A was detected after 15 min and the highest concentration (5.26 ± 0.58 µg/L) was observed at 30 min. In the brain tissue sample, 77.45 ± 0.58 µg/L of erinacine A was found. In the study of metabolites, there were 6 identical metabolites in plasma and brain tissue. To our surprise, erinacine B was found to be the metabolite of erinacine A, and its concentration increased over time as erinacine A was metabolized. In summary, this study is the first to demonstrate that erinacine A can be found in the cerebrospinal fluid of landrace pigs. Additionally, the metabolite identification of erinacine A in landrace pigs is also investigated.

Clinical guidance based on MRI for the management of temporomandibular joint synovial chondromatosis: One institution's experience.

The aim of this retrospective observational study was to introduce a comprehensive MRI evaluation criterion for the clinical management of synovial chondromatosis of the temporomandibular joint (TMJ-SC). Patients received different treatments according to the MRI evaluation system: bone erosion, extent, articular disc condition, location, maturity, and size of loose body. At least a 2-year follow-up was completed to assess tumor recurrence, visual analogue scale score for pain (VAS) and maximum interincisal opening (MIO). Of the 195 patients included for TMJ-SC, 34 received arthroscopy and 161 received open surgery. Among the patients with significant extent of SC, 32 received temporary resection of the condylar neck or zygomatic arch and 2 received treatment combined with ear, nose and throat(ENT). 28 received articular disc reconstruction and 56 received disc repositioning. Patients showed good recovery of joint function with only two cases of tumor recurrence at an average follow-up of 75.1 months after surgery. The MIO had improved from 30.2 mm to 40.0 mm(P < 0.0001) and VAS had decreased from 5.1 to 0.78(P < 0.0001).The preoperative MRI evaluation principles has been effective in selecting appropriate surgical options.

Microgel Encapsulated Mesoporous Silica Nanoparticles for Releasing Wnt16 to Synergistically Treat Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a commonly encountered degenerative joint disease in oral and maxillofacial surgery. Recent studies have shown that the excessive unbalanced activation of Wnt/ß-catenin signaling is connected with the pathogenesis of TMJOA and due to the inability to inhibit the over-activated Wnt pathway, while Wnt16-deficient mice has a more severe Knee OA. However, the efficacy of direct intra-TMJ injection of Wnt16 for the relief of TMJOA is still not directly confirmed. Moreover, small-molecule drugs such as Wnt16 usually exhibit short-lived efficacy and poor treatment adherence. Therefore, in order to obtain a stable release of Wnt16 both in the short and long term, this study fabricates a double-layer slow-release Wnt16 carrier based on mesoporous silica nanospheres (MSNs) encased within hyaluronic acid (HA) hydrogels. The biofunctional hydrogel HA/Wnt16@MSN is analyzed both in vitro and in vivo to evaluate the treatment of TMJOA. As a result, it shows superior pro-cartilage matrix restoration and inhibition of osteoclastogenesis ability, and effectively inhibits the over-activation of the Wnt/ß-catenin pathway. Taken together, biofunctional hydrogel HA/Wnt16@MSN is a promising candidate for the treatment of TMJOA.

Curcumin Inhibits the Development of Pancreatic Cancer by Targeting the circ_0079440/miR-522-3p/EIF4A1 Pathway.

Pancreatic cancer (PC) is a common gastrointestinal cancer with high invasiveness and high mortality. Curcumin is a natural polyphenol with anti-tumor activity against different cancers, including PC. Curcumin has been verified to mediate the expression of circular RNAs (circRNAs) to inhibit tumor development. This study aimed to explore the function and regulatory mechanism of curcumin on circ_0079440 in PC. PC cells were treated with different concentrations of curcumin (0, 5, 10 or 15 µM) for 24 h. Gene expression in PC cells and tissues was detected using RT-qPCR. Cell malignant phenotypes were determined by functional assays. The levels of EMT-related proteins were tested using western blot. RNA interaction was determined using RNA pulldown assay, luciferase reporter assay and RIP assay. The results showed that curcumin suppressed cell proliferative, migratory, and invasive capabilities, and weakened epithelial-mesenchymal transition (EMT) in a concentration-dependent way. Circ_0079440 was expressed at a high level in PC and its level was reduced via curcumin administration in PC cells. Rescue assays showed that circ_0079440 overexpression reversed the suppressive effects of curcumin on PC cell malignant phenotypes. Furthermore, in the xenograft mouse models, curcumin treatment inhibited tumor growth and metastasis, and circ_0079440 upregulation reversed the function of curcumin. Additionally, circ_0079440 was revealed to bind to miR-522-3p to upregulate eukaryotic initiation factor 4A1 (EIF4A1) expression in PC cells. EIF4A1 expression was also downregulated by curcumin, and EIF4A1 overexpression abolished the suppressive functions of curcumin. Moreover, EIF4A overexpression or miR-522-3p inhibition counteracted the anti-tumor effects of circ_0079440 depletion on PC development. To sum up, curcumin suppresses PC development by targeting the circ_0079440/miR-522-3p/EIF4A1 pathway, which might provide novel therapeutic targets for treatment of PC.

Comparative effectiveness of perioperative physical activity in older adults with lung cancer and their family caregivers: design of a multicenter pragmatic randomized trial.

BACKGROUND: With a median age at diagnosis of 70, lung cancer remains a significant public health challenge for older Americans. Surgery is a key component in treating most patients with non-metastatic lung cancer. These patients experience postoperative pain, fatigue, loss of respiratory capacity, and decreased physical function. Data on quality of life (QOL) in older adults undergoing lung cancer surgery is limited, and few interventions are designed to target the needs of older adults and their family caregivers (FCGs). The primary aim of this comparative effectiveness trial is to determine whether telephone-based physical activity coaching before and after surgery will be more beneficial than physical activity self-monitoring alone for older adults and their FCGs. METHODS: In this multicenter comparative effectiveness trial, 382 older adults (≥ 65 years) with lung cancer and their FCGs will be recruited before surgery and randomized to either telephone-based physical activity coaching or physical activity self-monitoring alone. Participants allocated to the telephone-based coaching comparator will receive five telephone sessions with coaches (1 pre and 4 post surgery), an intervention resource manual, and a wristband pedometer. Participants in the self-monitoring only arm will receive American Society of Clinical Oncology (ASCO) physical activity information and wristband pedometers. All participants will be assessed at before surgery (baseline), at discharge, and at days 30, 60, and 180 post-discharge. The primary endpoint is the 6-minute walk test (6MWT) at 30 days post-discharge. Geriatric assessment, lower extremity function, self-reported physical function, self-efficacy, and QOL will also be assessed. DISCUSSION: The trial will determine whether this telephone-based physical activity coaching approach can enhance postoperative functional capacity and QOL outcomes for older adults with lung cancer and their FCGs. Trial results will provide critical findings to inform models of postoperative care for older adults with cancer and their FCGs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06196008.

The Gender Gap in the Relationship between Metabolic Syndrome and Restrictive Ventilatory Defects.

BACKGROUND: Given the fundamental physiological differences between the sexes, this study aimed to investigate the effect of metabolic syndrome on ventilatory defects stratified by sex. METHODS: We conducted a nationwide, pooled, cross-sectional study. Data from 45,788 participants (men, n = 15,859; women, n = 29,929) aged 30 years or more were obtained from the Taiwan Biobank. Age-sex-adjusted and multivariate logistic regression models were used to estimate the risk of developing impaired pulmonary function (restrictive or obstructive ventilatory defects) in individuals with or without metabolic syndromes. Separate models were also used to estimate the effect of metabolic syndrome scores and the effect of individual metabolic abnormalities on the risk of restrictive ventilatory defects. RESULTS: The overall prevalence of metabolic syndrome was estimated to be 15.9% in Taiwan, much higher in men than in women (18.6% versus 14.4%). A significant association was observed between metabolic syndromes and the risk of restrictive ventilatory defects. The risk of developing a restrictive ventilator defect was 35% higher in participants with metabolic syndromes (odds ratio, 1.35; 95% confidence interval, 1.26-1.45) than in those without metabolic syndromes. Elevated blood pressure and a triglycerides abnormality were important predictors of restrictive ventilator defects. Sex-stratified subgroup analyses of the individual metabolic abnormalities indicated that men with abdominal obesity and women with dysglycemia were more likely to develop restrictive ventilatory defects. CONCLUSIONS: Our study's evidence suggested that metabolic syndromes were important predictors of impaired pulmonary function and an increased risk of developing restrictive ventilatory defects, and its risk increased with increasing numbers of metabolic abnormalities.

Polyethylene glycol-decorated n-type conducting polymers with improved ion accessibility for high-performance organic electrochemical transistors.

High-performance n-type organic mixed ionic-electronic conductors (OMIECs) are essential for advancing complementary circuits based on organic electrochemical transistors (OECTs). Despite significant progress, current n-type OMIECs often exhibit lower transconductance and slower response times compared to their p-type counterparts, limiting the development of OECT-based complementary circuits. Optimizing the conjugated backbone and side chain structures of OMIECs is critical for enhancing both ion and electron transport efficiencies while maintaining a delicate balance between the two. In this study, hydrophilic polyethylene glycol (PEG) side chains were incorporated into the highly conductive n-type polymer poly(3,7-dihydrobenzo[1,2-b:4,5-b']difuran-2,6-dione) (PBFDO) backbone to achieve this goal. The incorporation of PEG chains improved ion accessibility, and by adjusting the PEG content, the electronic and ionic transport properties were fine-tuned, ultimately enhancing the performance of OECTs and related p-n complementary circuits. The n-type OECTs based on PBFDO-PEG50wt% demonstrated exceptional transfer characteristics, including a transient response time (τON) as low as 72 µs, a high geometry-normalized transconductance exceeding 400 S cm-1, and an impressive µC* value surpassing 720 F cm-1 V-1 s-1. Notably, the use of PBFDO-PEG50wt% in a complementary inverter resulted in a voltage gain of 20 V/V, more than five times higher than that achieved with unmodified PBFDO (<4 V/V). These findings highlight the importance of balancing electron and ion transport characteristics in OMIECs to achieve high performance in OECTs and their associated circuits, and they validate PEG decoration as an effective approach.

Comparative genomics reveals ample evidence to Ganoderma sinense cultivars for molecular identification and new FIP exploration.

The first dikaryotic genome of Ganoderma cultivar Zizhi S2 (56.76 Mb, 16,681 genes) has been sequenced recently. 98.15% of complete BUSCOs were recovered in this genome assembly and high-confidence annotation rate improved to 91.41%. Collinearity analysis displayed the nuclear genome were 80.2% and 93.84% similar to reference genome of G. sinense at nucleotide and amino acid levels, which presented 8,521 core genes and 880 unique orthologous gene groups. Among that, at least six functional genes (tef1-α, ß-tubulin, rpb2, CaM, Mn-SOD and VeA) and a newly discovered fip gene were highly similar 99.27% ∼100% to those in reference genome. And the mt-LSU, mt-SSU and 13 PCGs in their mitogenome were also highly conserved with 99.27%-99.87% and 99.08%-100% identity, respectively. So that, this cultivar Zizhi S2 is confirmed conspecific with Ganoderma sinense (NCBI: txid1077348). The new fip gene (MN635280.1_336bp) existing a novel mutation which can be reflected on the phylogenetic tree and 3-dimensional model topology structure.

Screening and Characterization of a New Iflavirus Virus in the Fruit Tree Pest Pyrops candelaria.

Pyrops candelaria is one of the common pests of fruit trees, but the research on the pathogenic microorganisms it may carry is very limited. Therefore, it is essential to reveal the pathogenic microbes it carries and their potential hazards. This study found a new virus from the transcriptome of P. candelaria, which was first reported in P. candelaria and named PyCaV (Pyrops candelaria associated virus). RACE and bioinformatics assay revealed that the full length of PyCaV is 10,855 bp with the polyA tail, containing a single open-reading frame (ORF) encoding a polyprotein consisting of 3171 amino acid (aa). The virus has a typical iflavirus structure, including two rhv domains, an RNA helicase domain (HEL), a 3C cysteine protease domain (Pro), and an RNA-dependent RNA polymerase domain (RdRp). Further phylogenetic analysis revealed that this virus belongs to family Iflaviridae and sequence alignments analysis suggested PyCaV is a new member in an unassigned genus of family Iflaviridae. Further in-depth analysis of the virus infection showed that PyCaV is distributed throughout the whole P. candelaria, including its head, chest, and abdomen, but more PyCaV was identified in the chest. The distribution of PyCaV in different parts of P. candelaria was further explored, which showed that more PyCaV was detected in its piercing-sucking mouthparts and chest viscera. Statistical analysis showed that the PyCaV infection was affected by time and location.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry.

BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

A Polymeric Two-in-One Electron Transport Layer and Transparent Electrode for Efficient Indoor All-Organic Solar Cells.

Transparent electrodes (TEs) are vital in optoelectronic devices, enabling the interaction of light and charges. While indium tin oxide (ITO) has traditionally served as a benchmark TE, its high cost prompts the exploration of alternatives to optimize electrode characteristics and improve device efficiencies. Conducting polymers, which combine polymer advantages with metal-like conductivity, emerge as a promising solution for TEs. This work introduces a two-in-one electron transport layer (ETL) and TE based on films of polyethylenimine ethoxylated (PEIE)-modified poly(benzodifurandione) (PBFDO). These PEIE-modified PBFDO layers exhibit a unique combination of properties, including low sheet resistance (130 Ω sq-1), low work function (4.2 eV), and high optical transparency (>85% in the UV-vis-NIR range). In contrast to commonly used poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), the doping level of PBFDO remains unaffected by the PEIE treatment, as verified through UV-vis-NIR absorption and X-ray photoelectron spectroscopy measurements. When employed as a two-in-one ETL/TE in organic solar cells, the PEIE-modified PBFDO electrode exhibits performance comparable to conventional ITO electrodes. Moreover, this work demonstrates all-organic solar cells with record-high power conversion efficiencies of >15.1% under indoor lighting conditions. These findings hold promise for the development of fully printed, all-organic optoelectronic devices.

Increasing the Maximum Detectable Flow Velocity in High-Frequency Ultrasound Vector Doppler Imaging.

High-frequency ultrasound (HFUS; >30 MHz) Doppler imaging has been widely used in the imaging of small animals and humans because of its high resolution. Vector Doppler imaging (VDI) has certain advantages for visualizing complex flow patterns independent of the Doppler angle. However, no commercial HFUS VDI system is currently available; therefore, several studies have connected an ultrasound research platform (Verasonics Vantage 256) with an HFUS array transducer for HFUS VDI. Unfortunately, the maximum frame rate of this system is only 10 kHz at an operational frequency of 40 MHz because of limitations related to data transmission hardware, thereby restricting the maximum detectable velocity of Doppler measurements. To address this drawback, in the present study, an electrocardiography (ECG)-gating-based HFUS VDI system was developed to avoid Doppler flow aliasing in data acquisition by ultrasound research platform at its maximum frame rate of 10 kHz. The developed method aligns all tilted plane waves with the ECG R-wave, which avoids the trade-off between frame rate and tilted angles number in conventional VDI. The performance of the proposed data acquisition method in HFUS VDI was verified using a steady-flow phantom, for which estimation errors were less than 10% under different flow settings. In animal studies, peak flow velocities in the carotid artery, left ventricle, and aortic arch of wild-type mice were measured (approximately 55, 655, and 765 mm/s, respectively). Also, the HFUS VDI from the mitral regurgitation mice model was obtained to present the complex flow patterns through the proposed method. In contrast to the conventional method, no Doppler aliasing occurs in the proposed method because the frame rate is sufficient. The experimental results indicate the developed HFUS VDI has the potential to become a useful tool for vector flow visualization in small animals, even under a high flow velocity.

The associations between interparental conflict and adolescent adjustment: a cross-lagged panel network analysis.

Extensively studied in interparental relationship literature suggests interparental conflict is a risk factor for adolescent adjustment, but the specific, dimension level relationships between interparental conflict and adolescent adjustment remain unclear. This study explored the interactions between the various dimensions of interparental conflict and adolescent adjustment in Chinese adolescents. A total of 1870 Chinese adolescents (42.27% males; Mage = 16.18, SD = 0.43, range = 15-18) completed a survey at two time points spaced three months apart. Data was analyzed using both cross-sectional and longitudinal network analysis. The cross-sectional network analysis found that resolution has the greatest connections with the dimensions of adolescent adjustment, suggesting that adolescents reporting high resolution are more prone to experience concurrent poor adjustment and therefore should be a primary focus of attention. The longitudinal network analysis revealed that, in general, previous hyperactivity-inattention is a significant and strong predictor of future interparental conflict, underscoring a child-driven effect. Meanwhile, prosocial behavior contributes to decreases in both interparental conflict and adjustment problems over time. These findings highlight the importance of addressing hyperactivity-inattention and cultivating prosocial behavior in adolescents as key intervention points-these can help resolve conflicts between parents and reduce adjustment problems for adolescents.

A preliminary investigation of dissociation between subjective cognitive complaints and objective cognitive impairments in female patients with fibromyalgia: a role of information processing speed.

OBJECTIVES: Fibromyalgia (FM) is a chronic condition characterised by widespread pain, and cognitive difficulties represent one of the most common symptoms of FM. However, subjective cognitive complaints (SCC) may not necessarily indicate significant abnormalities in objective cognitive performances, and there is limited research investigating the relationship between these two aspects. This study thus aims to analyse the differences between SCC and objective cognitive performance in FM patients and to explore their associations. METHODS: A total of 32 FM female patients (age: 50.91±7.06; years since diagnosis: 4.34±4.53) recruited in this study underwent a comprehensive assessment covering four domains: pain, depression, trait anxiety, SCC, and objective cognitive functions (memory, executive function, and information processing speed). RESULTS: Eighty-seven percent of patients experienced significant negative impacts from pain; meanwhile, 91% and 62% showed marked tendencies towards trait anxiety and depression, respectively. Additionally, 56% of patients reported significantly higher levels of SCC. However, less than one-third of patients demonstrated impairments in various cognitive functions. SCC significantly correlated with pain intensity, depression, information processing speed, and trait anxiety, with pain intensity being a significant predictor (R2=.30). Furthermore, patients with significant SCC exhibited more abnormalities in pain, information processing speed, and trait anxiety compared to those without significant SCC. CONCLUSIONS: SCC may not necessarily correlate with objective cognitive impairments and might be specifically linked to defective information processing speed. It thus merits that clinical assessments for FM patients should incorporate measurements of information processing speed to gain a comprehensive understanding of SCC in FM patients.

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.

Interleukin 23 versus interleukin 12/23 inhibitors on preventing incidental psoriatic arthritis in patients with psoriasis? A real-world comparison from the TriNetX Global Collaborative Network.

BACKGROUND: Managing psoriasis (PsO) and its comorbidities, particularly psoriatic arthritis, often involves using interleukin (IL)-23 and IL-12/23 inhibitors. However, the comparative risk of these treatments still needs to be explored. OBJECTIVE: This study evaluates the risk of developing psoriatic arthritis in patients treated with IL-23 inhibitors compared to IL-12/23 inhibitors. METHODS: This retrospective cohort study utilized data from the TriNetX, including adult patients diagnosed with PsO. Patients with IL-23 or IL-12/23 inhibitors treatment were included and propensity score matched. The primary outcome was the incidence of psoriatic arthritis (PsA), analyzed using a Cox regression hazard model and Kaplan-Meier estimates. RESULTS: The study included matched cohorts of patients treated with IL-23 inhibitors (n = 2273) and IL-12/23 inhibitors (n = 2995). Cox regression analysis revealed no significant difference in the cumulative incidence of PsA between the IL-23i and IL-12/23i cohorts (P = .812). Kaplan-Meier estimates confirmed similar cumulative incidences of arthropathic PsO in both cohorts over the study period. LIMITATION: Long-term follow-up studies are required to understand more of the effects of these interleukin inhibitors. CONCLUSION: No significant difference but a numerically lower risk of psoriatic arthritis in PsO patients treated with IL-23 inhibitors than with IL-12/23 inhibitors was found, underscoring their comparable efficacy in PsO management and follow-up.

Multi-Omics Characterization of E3 Regulatory Patterns in Different Cancer Types.

Ubiquitination, a post-translational modification, refers to the covalent attachment of ubiquitin molecules to substrates. This modification plays a critical role in diverse cellular processes such as protein degradation. The specificity of ubiquitination for substrates is regulated by E3 ubiquitin ligases. Dysregulation of ubiquitination has been associated with numerous diseases, including cancers. In our study, we first investigated the protein expression patterns of E3 ligases across 12 cancer types. Our findings indicated that E3 ligases tend to be up-regulated and exhibit reduced tissue specificity in tumors. Moreover, the correlation of protein expression between E3 ligases and substrates demonstrated significant changes in cancers, suggesting that E3-substrate specificity alters in tumors compared to normal tissues. By integrating transcriptome, proteome, and ubiquitylome data, we further characterized the E3-substrate regulatory patterns in lung squamous cell carcinoma. Our analysis revealed that the upregulation of the SKP2 E3 ligase leads to excessive degradation of BRCA2, potentially promoting tumor cell proliferation and metastasis. Furthermore, the upregulation of E3 ubiquitin-protein ligase TRIM33 was identified as a biomarker associated with a favorable prognosis by inhibiting the cell cycle. This work exemplifies how leveraging multi-omics data to analyze E3 ligases across various cancers can unveil prognosis biomarkers and facilitate the identification of potential drug targets for cancer therapy.

DrugRepoBank: a comprehensive database and discovery platform for accelerating drug repositioning.

In recent years, drug repositioning has emerged as a promising alternative to the time-consuming, expensive and risky process of developing new drugs for diseases. However, the current database for drug repositioning faces several issues, including insufficient data volume, restricted data types, algorithm inaccuracies resulting from the neglect of multidimensional or heterogeneous data, a lack of systematic organization of literature data associated with drug repositioning, limited analytical capabilities and user-unfriendly webpage interfaces. Hence, we have established the first all-encompassing database called DrugRepoBank, consisting of two main modules: the 'Literature' module and the 'Prediction' module. The 'Literature' module serves as the largest repository of literature-supported drug repositioning data with experimental evidence, encompassing 169 repositioned drugs from 134 articles from 1 January 2000 to 1 July 2023. The 'Prediction' module employs 18 efficient algorithms, including similarity-based, artificial-intelligence-based, signature-based and network-based methods to predict repositioned drug candidates. The DrugRepoBank features an interactive and user-friendly web interface and offers comprehensive functionalities such as bioinformatics analysis of disease signatures. When users provide information about a drug, target or disease of interest, DrugRepoBank offers new indications and targets for the drug, proposes new drugs that bind to the target or suggests potential drugs for the queried disease. Additionally, it provides basic information about drugs, targets or diseases, along with supporting literature. We utilize three case studies to demonstrate the feasibility and effectiveness of predictively repositioned drugs within DrugRepoBank. The establishment of the DrugRepoBank database will significantly accelerate the pace of drug repositioning. Database URL:  https://awi.cuhk.edu.cn/DrugRepoBank.