Clinical factors and predictors for spontaneous separation of epiretinal membranes.

PURPOSE: To investigate the clinical characteristics, imaging features, and predictive factors for spontaneous separation in patients with idiopathic or secondary ERM. METHODS: The overall cohort was divided into two subgroups: idiopathic ERM (28 eyes, 56%) and secondary ERM (22 eyes, 44%). Electronic records and multimodal imaging were reviewed. RESULTS: Among the 50 eyes included in this study, the self-separation of ERM occurred over a mean duration of 28.1 ± 25.3 months (median: 25.4 months). Compared with the secondary ERM group, the idiopathic group had a shorter interval to separation (idiopathic vs. secondary, 23.4 vs. 34.1 months, respectively; P = .01) and better vision at diagnosis (logMAR 0.094 vs. 0.224; P = .009) and after separation (logMAR 0.097 vs. 0.188; P = .01). Overall, in both subgroups, spontaneous ERM separation appeared to have been induced by posterior vitreous detachment (PVD) (P < .001). Multivariate analysis revealed that the self-separation interval (odds ratio [OR] 0.936) and IRF (OR 0.049) were significantly associated with complete ERM separation (all P < .05). Additionally, secondary ERM (OR 15.224) and lower initial best-corrected visual acuity (OR 267.589) were significantly associated with improvements in vision after self-separation (all P < .05). CONCLUSION: The self-separation of ERM appears to be induced by PVD development in most eyes. Owing to the possibility of complete spontaneous separation, surgical membrane peeling may be delayed by up to 28 months in eyes without PVD, regardless of whether the cause is idiopathic or secondary. Patients with secondary ERM may experience favorable visual improvement after self-separation despite having poor vision at diagnosis and IRF on OCT. KEY MESSAGES: What is known • An epiretinal membrane (ERM), the most prevalent retinal disease in adults, is less understood regarding clinical factors and the accurate mechanism of spontaneous separation. What is new • The separation of ERM appears to be induced by PVD development in most eyes. • Favorable vision outcomes were associated with secondary ERMs and lower initial visual acuity. • Complete ERM separation was associated with a shorter self-resolution interval and the absence of intraretinal fluid (IRF) in OCT imaging.

Connectomic reconstruction predicts visual features used for navigation.

Many animals use visual information to navigate1-4, but how such information is encoded and integrated by the navigation system remains incompletely understood. In Drosophila melanogaster, EPG neurons in the central complex compute the heading direction5 by integrating visual input from ER neurons6-12, which are part of the anterior visual pathway (AVP)10,13-16. Here we densely reconstruct all neurons in the AVP using electron-microscopy data17. The AVP comprises four neuropils, sequentially linked by three major classes of neurons: MeTu neurons10,14,15, which connect the medulla in the optic lobe to the small unit of the anterior optic tubercle (AOTUsu) in the central brain; TuBu neurons9,16, which connect the AOTUsu to the bulb neuropil; and ER neurons6-12, which connect the bulb to the EPG neurons. On the basis of morphologies, connectivity between neural classes and the locations of synapses, we identify distinct information channels that originate from four types of MeTu neurons, and we further divide these into ten subtypes according to the presynaptic connections in the medulla and the postsynaptic connections in the AOTUsu. Using the connectivity of the entire AVP and the dendritic fields of the MeTu neurons in the optic lobes, we infer potential visual features and the visual area from which any ER neuron receives input. We confirm some of these predictions physiologically. These results provide a strong foundation for understanding how distinct sensory features can be extracted and transformed across multiple processing stages to construct higher-order cognitive representations.

Computed tomography radiomics models of tumor differentiation in canine small intestinal tumors.

Radiomics models have been widely exploited in oncology for the investigation of tumor classification, as well as for predicting tumor response to treatment and genomic sequence; however, their performance in veterinary gastrointestinal tumors remains unexplored. Here, we sought to investigate and compare the performance of radiomics models in various settings for differentiating among canine small intestinal adenocarcinoma, lymphoma, and spindle cell sarcoma. Forty-two small intestinal tumors were contoured using four different segmentation methods: pre- or post-contrast, each with or without the inclusion of intraluminal gas. The mesenteric lymph nodes of pre- and post-contrast images were also contoured. The bin settings included bin count and bin width of 16, 32, 64, 128, and 256. Multinomial logistic regression, random forest, and support vector machine models were used to construct radiomics models. Using features from both primary tumors and lymph nodes showed significantly better performance than modeling using only the radiomics features of primary tumors, which indicated that the inclusion of mesenteric lymph nodes aids model performance. The support vector machine model exhibited significantly superior performance compared with the multinomial logistic regression and random forest models. Combining radiologic findings with radiomics features improved performance compared to using only radiomics features, highlighting the importance of radiologic findings in model building. A support vector machine model consisting of radiologic findings, primary tumors, and lymph node radiomics features with bin count 16 in post-contrast images with the exclusion of intraluminal gas showed the best performance among the various models tested. In conclusion, this study suggests that mesenteric lymph node segmentation and radiological findings should be integrated to build a potent radiomics model capable of differentiating among small intestinal tumors.

Neuronal parts list and wiring diagram for a visual system.

A catalogue of neuronal cell types has often been called a 'parts list' of the brain1, and regarded as a prerequisite for understanding brain function2,3. In the optic lobe of Drosophila, rules of connectivity between cell types have already proven to be essential for understanding fly vision4,5. Here we analyse the fly connectome to complete the list of cell types intrinsic to the optic lobe, as well as the rules governing their connectivity. Most new cell types contain 10 to 100 cells, and integrate information over medium distances in the visual field. Some existing type families (Tm, Li, and LPi)6-10 at least double in number of types. A new serpentine medulla (Sm) interneuron family contains more types than any other. Three families of cross-neuropil types are revealed. The consistency of types is demonstrated by analysing the distances in high-dimensional feature space, and is further validated by algorithms that select small subsets of discriminative features. We use connectivity to hypothesize about the functional roles of cell types in motion, object and colour vision. Connectivity with 'boundary types' that straddle the optic lobe and central brain is also quantified. We showcase the advantages of connectomic cell typing: complete and unbiased sampling, a rich array of features based on connectivity and reduction of the connectome to a substantially simpler wiring diagram of cell types, with immediate relevance for brain function and development.

Incidence of intraocular inflammation and its risk factors in patients treated with brolucizumab: a nationwide cohort study.

This study aimed to evaluate the incidence of clinically significant intraocular inflammation (csIOI) after treatment with intravitreal injection (IVI) of brolucizumab and identify csIOI risk factors. We categorized 60,966 South Korean patients from a nationwide population-based cohort into 4 groups: groups 1 (Ranibizumab), 2 (Aflibercept), 3 (Brolucizumab), and 4 (switched to brolucizumab). We used the Kaplan-Meier method to estimate the cumulative incidence of csIOI in each group and calculated the hazard ratios (HRs) and 95% confidence intervals (CIs). We constructed a multivariate model using forward selection methods to identify risk factors for csIOI. The cumulative incidence of csIOI within 180 days of the index date in groups 1, 2, 3, and 4 was 0.36% (67/18,537), 0.49% (186/37,951), 3.47% (38/1,095), and 3.69% (125/3,383), respectively. Multivariate analysis revealed a significant increase in csIOI risk in groups 3 (HR 11.08, 95% CI 7.42-16.53, P < 0.001) and 4 (HR 10.40, 95% CI 7.67-14.09, P < 0.001). History of retinal vascular occlusion (HR 1.56, 95% CI 1.01-2.40, P = 0.043) significantly increased csIOI risk after brolucizumab IVI treatment; female sex (HR 0.78, 95% CI 0.64-0.96, p = 0.020) and diabetes (HR 0.72, 95% CI 0.58-0.90, p = 0.004) decreased the risk. csIOI incidence was higher after brolucizumab IVI treatment than after ranibizumab and aflibercept IVI treatment. Retinal vein occlusion history, female sex, and diabetes are associated with csIOI after brolucizumab IVI treatment.

Controlled chemical transformation of lignin by nitric acid treatment and carbonization.

This study focuses on understanding the chemical reactions and results of Kraft lignin transformation through nitric acid treatment and subsequent carbonization. With its rich carbon content, lignin stands out as a promising candidate for the manufacturing of high-value carbon materials. The lignin underwent effective nitration, depolymerization, and oxidation under ambient conditions and at 40 °C, while a slight increase in reaction temperature significantly reduced the reaction time. The molecular weight Mw was effectively reduced from 4371 g/mol to 767 g/mol. The acid-treated lignin samples with incorporated nitro groups were further carbonized to create nitrogen-doped carbon structures. The resulting materials show stable nitrogen content (about at 5 wt%) even after carbonization due to the transformation of nitro groups into thermally stable pyridinic moieties, thereby exhibiting enhanced electrocatalytic properties compared to nitrogen-free carbon materials derived from Kraft lignin. The nitric acid-assisted treatment of lignin obviates the need for catalysts, and additional extraction or purification steps for preparing bio-derived carbon precursors, rendering it facile, fast, and cost-efficient.

Risk factors of thromboembolic events in patients with scrub typhus.

BACKGROUND: Thromboembolic events are a well-recognized cause of in-hospital deaths of patients with infectious diseases. However, thromboembolic events in patients with scrub typhus, caused by Orientia tsutsugamushi have rarely been reported. This study aimed to assess risk factors associated with thromboembolic events in patients with scrub typhus. METHODS: All 93 scrub typhus patients' diagnoses were confirmed serologically or by positive nested polymerase chain reaction (PCR). The clinical and laboratory findings from 12 scrub typhus patients with thromboembolic events and 81 scrub typhus patients with nonthromboembolic events were retrospectively studied. To determine the factors implicated in thromboembolic events, we performed multivariate logistic regression analysis using the six independent factors identified by the univariate analysis. FINDINGS: The mean age of the patients in the thromboembolic group was 76.4 years (median, 76 years), and in nonthromboembolic group it was 64.6 years (median, 65 years) (P<0·001). Thromboembolic events were observed in 12 patients. These events included acute coronary syndrome (n = 5), acute limb ischemia (n = 4), ischemic stroke (n = 1), deep vein thrombosis combined with pulmonary thromboembolism (n = 1), and left common iliac artery aneurysm with a thrombus (n = 1). According to multivariate analysis, the following four factors were significantly associated with the thromboembolic events: 1) treatment with rifampin (OR = 57.6; CI 1.2-2700.3), 2) Taguchi genotype (OR = 41.5, P = 0.028; CI 1.5-1154.6), 3) atrial fibrillation (OR = 9.4, P = 0.034; CI 1.2-74.0), and 4) age (OR = 1.1, P = 0.046; CI 1.0-1.3). CONCLUSIONS: Our study suggests that clinicians should be cautious when managing patients with scrub typhus to avoid the development of thromboembolic events, especially in patients with risk factors such as treatment with rifampin, Taguchi genotype, atrial fibrillation, and advanced age.

Safety and efficacy of canine gonadal tissue-derived mesenchymal stem cells for early myxomatous mitral valve disease.

Introduction: This study explored the potential efficacy and safety of therapy with mesenchymal stem cells (MSC) derived from gonadal tissue to address the early stage of myxomatous mitral valve disease (MMVD), the predominant cardiac condition in dogs. Methods: Sixteen dogs diagnosed with MMVD B1 were enrolled in this trial and assigned to either a control group (control group, n = 10) or a group that received MSC derived from gonadal tissue (treatment group, n = 6). In the treatment group, allogeneic MSC derived from gonadal tissue (1 × 106 cells/kg) were intravenously administered at monthly intervals for five or more sessions. Data were compared at baseline and at the endpoint 1-year intervals. The efficacy was assessed using echocardiography, thoracic radiography, NT-proBNP, and the duration from B1 diagnosis to B2 transition to evaluate its effect on MMVD stage progression. Safety was evaluated through physical examinations, blood tests, imaging studies, and monitoring of adverse events. Results: After 1 year of observation, the control group exhibited deteriorating echocardiographic parameters, whereas the treatment group displayed no substantial differences between baseline and endpoint measurements. Notably, a statistically significant disparity was noted in the left atrial diameter (p < 0.05) and E-wave velocity (p < 0.05) between the two groups, indicating a favorable impact of MSC derived from the gonadal tissue on left atrial pressure. Additionally, in contrast to the control group, the treatment group demonstrated delayed progression to MMVD stage B2, enabling them to prolong their disease duration without requiring cardiac medication (p = 0.038). In quality of life (QoL) metrics following MSC treatment, appetite showed a statistically significant improvement, increasing from 4 to 4.83 (p < 0.05). Discussion: Treatment with gonadal tissue-derived MSCs significantly delayed MMVD stage progression, highlighting the broad potential of MSC derived from gonadal tissue for treating complex veterinary conditions.

Heterologous immunization targeting the CST1 antigen confers better protection than ROP18 in mice.

Aim: To evaluate the protective efficacy induced by heterologous immunization with recombinant baculoviruses or virus-like particles targeting the CST1 and ROP18 antigens of Toxoplasma gondii.Materials & methods: Recombinant baculovirus and virus-like particle vaccines expressing T. gondii CST1 or ROP18 antigens were developed to evaluate protective immunity in mice upon challenge infection with 450 Toxoplasma gondii (ME49).Results: Immunization with CST1 or ROP18 vaccines induced similar levels of T. gondii-specific IgG and IgA responses. Compared with ROP 18, CST1 vaccine showed better antibody-secreting cell response, germinal center B cell activation, and significantly reduced brain cyst burden and body weight loss.Conclusion: Our findings suggest that CST1 heterologous immunization elicited better protection than ROP18, providing important insight into improving the toxoplasmosis vaccine design strategy.

[Box: see text].

Incidence and Risk of Depressive Disorder in Patients With Retinitis Pigmentosa.

Importance: There is a lack of large-scale clinical studies exploring mental health among patients with retinitis pigmentosa (RP). Additionally, few studies have evaluated the associations of visual impairment with mental health in young patients. Objective: To investigate the association between depressive disorder and RP. Design, Setting, and Participants: This was a retrospective, nationwide, population-based cohort study using data obtained from the Health Insurance Review and Assessment service in Korea between 2008 and 2022. A total of 10 879 individuals who were newly diagnosed with RP between January 2011 and December 2021, as verified by both the RP registration code (National Registry of Rare and Intractable Disease in Korea code V209) and diagnostic code (International Statistical Classification of Diseases, 10th Revision code H35.51), were included. Data analysis was performed from October 2023 to January 2024. Exposure: Diagnosis of RP. Main Outcomes and Measures: Participants were categorized into 3 groups based on age at diagnosis (<20, 20-39, and ≥40 years). The incidence of depressive disorder in RP was determined after excluding those diagnosed with depressive disorder prior to RP diagnosis. Age- and sex-adjusted standardized incidence ratios (SIRs) of depressive disorder in patients with RP compared with the general population were calculated. Subgroup analyses by sex and age group were conducted. Results: A total of 10 879 patients (638 aged <20 years, 2233 aged 20-39 years, and 8008 aged ≥40 years; 5710 [52.5%] female) newly diagnosed with RP between 2011 and 2021 were included. The 10-year cumulative incidence of depressive disorder was 17.67% (95% CI, 16.57%-18.84%) in patients with RP. Subgroup analysis showed higher incidence of depressive disorder in female patients (hazard ratio [HR], 1.46; 95% CI, 1.29-1.65; P < .001) and those aged 40 years or older (HR, 1.93; 95% CI, 1.63-2.29; P < .001). The overall SIR of depressive disorder in patients with RP was 1.19 (95% CI, 1.12-1.27; P < .001), indicating a higher risk of depressive disorder compared with that in the general population. Both male and female patients with RP showed increased incidence rates of depressive disorder (17.53 [95% CI, 15.91-19.27] and 25.57 [95% CI, 23.58-27.67] per 1000 person-years, respectively) and increased SIRs of depressive disorder (1.21 [95% CI, 1.10-1.33] and 1.18 [95% CI, 1.09-1.28], respectively) (all P < .001) compared with the general population. Subgroup analysis by age group showed that the SIR peaked in patients in their 20s (1.50; 95% CI, 1.17-1.90; P = .006) and aged 60 years or older (1.25; 95% CI, 1.14-1.37; P < .001). Conclusions and Relevance: Individuals diagnosed with RP had a higher risk of developing depressive disorder. These findings support consideration of providing emotional and social support to patients with RP.

Effect of abatacept versus conventional synthetic disease modifying anti-rheumatic drugs on rheumatoid arthritis-associated interstitial lung disease.

BACKGROUND/AIMS: To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation. RESULTS: The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable. CONCLUSION: Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.

Comparison of Recovery Rates of Sudden Sensorineural Hearing Loss by Age Group.

Background: While numerous studies have been conducted on sudden sensorineural hearing loss (SSNHL), research on how treatment outcomes and prognosis vary by age remains insufficient. This study aims to investigate the differences in recovery rates among SSNHL patients divided by age groups. Methods: A retrospective study was conducted on 177 patients diagnosed with SSNHL from 2020 to 2023. The patients were categorized into four age groups: under 20, 30-40, 50-60, and over 70. Recovery rates and associated symptoms were compared across these groups. Results: Significant recovery rates were observed in all age groups except for those over 70 (p = 0.006, p = 0.003, p = 0.009). No significant differences were found in recovery rates based on gender (p > 0.75) or symptoms such as tinnitus, ear fullness, and dizziness (p > 0.05). Conclusions: The study revealed that younger and middle-aged adults showed statistically significant improvements in recovery rates, while the elderly exhibited relatively lower recovery rates.

Orally dissolving film as a potential vaccine delivery carrier to prevent influenza virus infection.

Orally dissolving films (ODF) are designed to be dissolved on the tongue and absorbed in the mouth. It offers multiple advantages over the commonly used needle-based vaccines, especially in terms of convenience allowing safe, painless, and easy self-administration. As the efficacy of ODF-encapsulated influenza vaccines has not been demonstrated, we assessed the protection elicited by inactivated influenza virus (A/PR/8/34, H1N1) vaccine delivered using ODFs in mice. Trehalose and pullulan components of the ODF ensured that the HA antigens of the inactivated PR8 virus retained their stability while ensuring the rapid release of the vaccines upon exposure to murine saliva. Mice were immunized thrice by placing the PR8-ODF on the tongues of mice at 4-week intervals, and vaccine-induced protection was evaluated upon lethal homologous challenge infection. The PR8-ODF vaccination elicited virus-specific serum IgG and IgA antibody responses, hemagglutinin inhibition (HAI), and viral neutralization. Upon challenge infection, ODF vaccination showed higher levels of IgG and IgA antibody responses in the lungs and antibody-secreting cell (ASC) responses in both lung and spleen compared to unimmunized controls. These results corresponded with the enhanced T cell and germinal center B cell responses in the lungs and spleens. Importantly, ODF vaccination significantly reduced lung virus titers and inflammatory cytokines (IFN-γ, IL-6) production compared to unvaccinated control. ODF vaccination ensured 100% survival and prevented weight loss in mice. These findings suggest that influenza vaccine delivery through ODFs could be a promising approach for oral vaccine development.

Forensic height estimation using polygenic score in Korean population.

Height is known to be a classically heritable trait controlled by complex polygenic factors. Numerous height-associated genetic variants across the genome have been identified so far. It is also a representative of externally visible characteristics (EVC) for predicting appearance in forensic science. When biological evidence at a crime scene is deficient in identifying an individual, the examination of forensic DNA phenotyping using some genetic variants could be considered. In this study, we aimed to predict 'height', a representative forensic phenotype, by using a small number of genetic variants when short tandem repeat (STR) analysis is hard with insufficient biological samples. Our results not only replicated previous genetic signals but also indicated an upward trend in polygenic score (PGS) with increasing height in the validation and replication stages for both genders. These results demonstrate that the established SNP sets in this study could be used for height estimation in the Korean population. Specifically, since the PGS model constructed in this study targets only a small number of SNPs, it contributes to enabling forensic DNA phenotyping even at crime scenes with a minimal amount of biological evidence. To the best of our knowledge, this was the first study to evaluate a PGS model for height estimation in the Korean population using GWAS signals. Our study offers insight into the polygenic effect of height in East Asians, incorporating genetic variants from non-Asian populations.

Development of a Fit-For-Purpose Multi-Marker Panel for Early Diagnosis of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) suffers from a lack of an effective diagnostic method, which hampers improvement in patient survival. Carbohydrate antigen 19-9 (CA19-9) is the only FDA-approved blood biomarker for PDAC, yet its clinical utility is limited due to suboptimal performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics for the discovery, verification, and validation of novel biomarkers. A plethora of protein biomarker candidates for PDAC have been identified using LC-MS, yet few has successfully transitioned into clinical practice. This translational standstill is owed partly to insufficient considerations of practical needs and perspectives of clinical implementation during biomarker development pipelines, such as demonstrating the analytical robustness of proposed biomarkers which is critical for transitioning from research-grade to clinical-grade assays. Moreover, the throughput and cost-effectiveness of proposed assays ought to be considered concomitantly from the early phases of the biomarker pipelines for enhancing widespread adoption in clinical settings. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS protocol. In the discovery phase, we comprehensively surveyed putative PDAC biomarkers from both in-house data and prior studies. In the verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation tests. We adopted a high-throughput protocol including a short gradient (<10 min) and simple sample preparation (no depletion or enrichment steps). Additionally, we developed our assay using serum samples, which are usually the preferred biospecimen in clinical settings. We developed predictive models based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone in discriminating PDAC from non-PDAC controls including healthy individuals and patients with benign pancreatic diseases. A large-scale clinical validation is underway to demonstrate the clinical validity of our novel panel.

New Insights into Pacing Induced Cardiomyopathy.

Pacing induced cardiomyopathy (PICM) can occur as a complication due to pacing the right ventricle. Its precise definition varies across different studies, leading to uncertainty as to the best approach for managing this entity. More than 10% of patients who undergo chronic right ventricular pacing develop PICM. Risk factors associated with PICM include reduced left ventricular ejection fraction (LVEF), the proportion of right ventricular pacing, and paced QRS duration. The main approach to treating PICM has been upgrading to biventricular pacing cardiac resynchronization therapy when the LVEF decreases. However, emerging evidence suggest that conduction system pacing might provide an opportunity to manage PICM.

Efficacy assessment of miltefosine and curcumin against Clonorchis sinensis infection.

Praziquantel (PZQ) is currently the only approved drug for treating clonorchiasis, but its poor efficacy against Clonorchis sinensis larvae has highlighted the need to develop newer drugs. In this study, to address this challenge, we investigated the anti-parasitic efficacy of miltefosine (MLT), curcumin (CUR), and PZQ against C. sinensis metacercariae (CsMC), newly excysted juvenile worms (CsNEJs), and adults. Larvicidal effects of MLT and CUR surpassed those elicited by PZQ in vitro. These two drugs exerted their effect against both CsMC and CsNEJs in a dose- and time-dependent manner. To confirm the effect of these drugs in vivo, Syrian golden hamsters were orally infected with 100 CsMC and subsequently treated with MLT, CUR, or PZQ at 1 and 4 weeks post-infection (wpi). MLT and CUR reduced the worm recoveries at 1 and 4 wpi, indicating that these drugs were efficacious against both larvae and adult C. sinensis. PZQ was only efficacious against adult worms. Interestingly, both MLT and CUR showed lower levels of C. sinensis-specific IgG responses than the infection control group, implying that worm burden and bile IgG responses could be correlated. These results indicate that MLT and CUR are efficacious against both larval and adult stages of C. sinensis, thereby highlighting their potential for further development as alternative therapeutic options for clonorchiasis.

Real-World Incidence of Incident Noninfectious Uveitis in Patients Treated With BRAF Inhibitors: A Nationwide Clinical Cohort Study.

PURPOSE: To compare the incidence of noninfectious uveitis in skin melanoma or lung cancer patients who received BRAF inhibitors with that in those who received immune checkpoint inhibitors (ICIs) or conventional cytotoxic chemotherapy. DESIGN: Nationwide population-based retrospective clinical cohort study METHODS: From the Health Insurance Review and Assessment Service database of South Korea, we retrospectively defined 77,323 patients with skin melanoma or lung cancer who received BRAF inhibitor therapy (BRAF inhibitor-exposed group; n = 396), ICIs (ICI-exposed group; n = 22,474), or conventional cytotoxic chemotherapy (unexposed group; n = 54,453). We calculated the 1-year cumulative incidence of noninfectious uveitis in each group from the first day of BRAF inhibitor, ICI, or cytotoxic agent administration. RESULTS: During the first year of treatment initiation, the cumulative incidence of uveitis was 0.33%, 0.35%, and 2.27% in the unexposed, ICI-exposed, and BRAF inhibitor-exposed groups, respectively. Adjusted hazard ratios (aHR) indicated a 7.52-fold and 5.68-fold increased risk of uveitis in the BRAF inhibitor-exposed group compared with that in the unexposed and ICI-exposed groups (95% confidence interval [CI] 3.83-14.75, P < .001 and 95% CI 2.81-11.47, P < .001, respectively). After 1:4 propensity score matching, aHRs showed a 35.51-fold and 15.80-fold increased risk (95% CI 4.49-280.48, P = .001 and 95% CI 1.76-141.00, P = .014) of uveitis and severe uveitis, respectively, in the BRAF inhibitor-exposed versus unexposed patients. Crossover analysis within the BRAF inhibitor-exposed group showed a 3.71-fold increase in uveitis risk during 1-year post index date in comparison with 1-year prior to index date (95% CI 1.03-13.40, P = .046). In the BRAF inhibitor-exposed group, female sex, chronic kidney disease, and melanoma were associated with a trend of increased, albeit nonsignificant, risk of uveitis. CONCLUSIONS: Melanoma or lung cancer patients treated with BRAF inhibitors showed significantly higher risk of noninfectious uveitis than patients treated with conventional cytotoxic drugs or ICIs. These findings emphasize the importance of pretreatment patient education on BRAF-inhibitor-associated uveitis risk to enable prompt ophthalmic evaluation and treatment if symptoms arise during drug administration.

Comprehensive Overview of Alzheimer's Disease: Etiological Insights and Degradation Strategies.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and affects millions of individuals globally. AD is associated with cognitive decline and memory loss that worsens with aging. A statistical report using U.S. data on AD estimates that approximately 6.9 million individuals suffer from AD, a number projected to surge to 13.8 million by 2060. Thus, there is a critical imperative to pinpoint and address AD and its hallmark tau protein aggregation early to prevent and manage its debilitating effects. Amyloid-ß and tau proteins are primarily associated with the formation of plaques and neurofibril tangles in the brain. Current research efforts focus on degrading amyloid-ß and tau or inhibiting their synthesis, particularly targeting APP processing and tau hyperphosphorylation, aiming to develop effective clinical interventions. However, navigating this intricate landscape requires ongoing studies and clinical trials to develop treatments that truly make a difference. Genome-wide association studies (GWASs) across various cohorts identified 40 loci and over 300 genes associated with AD. Despite this wealth of genetic data, much remains to be understood about the functions of these genes and their role in the disease process, prompting continued investigation. By delving deeper into these genetic associations, novel targets such as kinases, proteases, cytokines, and degradation pathways, offer new directions for drug discovery and therapeutic intervention in AD. This review delves into the intricate biological pathways disrupted in AD and identifies how genetic variations within these pathways could serve as potential targets for drug discovery and treatment strategies. Through a comprehensive understanding of the molecular underpinnings of AD, researchers aim to pave the way for more effective therapies that can alleviate the burden of this devastating disease.