Expert Consensus on the Structure, Role, and Procedures of the Korea Expert Committee on Immunization Practices.

BACKGROUND: The Korea Expert Committee on Immunization Practices (KECIP) is a key advisory body the government to develop guidelines and provide technical advisory activities on immunization policies in Korea. A recent policy study, inspired by global best practices, aims to enhance KECIP's functionality for providing timely and transparent recommendations in the face of evolving vaccine science and emerging infectious diseases like COVID-19. METHODS: This study reviewed the current status of KECIP and collected expert opinions through surveys and consultations. Among the 40 panel members who were surveyed, 19 responded to a questionnaire specifically designed to assess the potential areas of improvement within KECIP. RESULTS: The majority of respondents favored maintaining the current member count and emphasized the need for a subcommittee. Opinions varied on issues such as the length of KECIP's term, the representation of vaccine manufacturers' perspectives, and the chairperson's role. However, there was a consensus on the importance of expertise, transparency, and fair proceedings within the committee. CONCLUSION: This study underscores the pivotal role of KECIP in shaping national immunization policies, emphasizing the necessity for informed guidance amidst evolving vaccine science and emerging infectious diseases. Furthermore, it stressed the importance of enhancing KECIP's capacity to effectively address evolving public health challenges and maintain successful immunization programs in South Korea.

Surgical Outcomes of Low-Flow Bypass Surgery in Intracranial Atherosclerotic Steno-Occlusive Diseases.

BACKGROUND AND OBJECTIVES: The role of bypass surgery in intracranial atherosclerotic steno-occlusive diseases (ICADs) remains controversial. We aimed to analyze the surgical outcomes of bypass surgery in patients with the ICADs in a single tertiary institution. METHODS: Among 1018 cases of low-flow bypass surgery between 2003 and 2022, 215 patients with the ICAD refractory to medical treatment were finally enrolled in this study. Clinical and radiological outcomes were retrospectively evaluated, with survival analyses. RESULTS: All strokes, cerebral infarctions, and intracranial hemorrhages occurred in 12.1% (n = 26), 9.8% (n = 21), and 2.3% (n = 5), respectively, during the clinical follow-up of 54.6 ± 47.6 months (range, 0.6-237.8 months). Among all stroke events, 84.6% (n = 22) occurred within 30 postoperative days. The 2-year and 5-year cumulative risks of all strokes were 12.1% each. The mean modified Rankin Scale scores were 1.6 ± 1.1 (range, 0-5) preoperatively and 0.8 ± 1.2 (range, 0-6) at last (P < .01). The patency of direct bypass was 99.1% (n = 213) just before discharge and 96.3% (n = 184 of 191 patients with available tests) at the last angiographic follow-up of 27.0 ± 27.3 months (range, 2.3-97.3 months). All the patients with available data (n = 190) showed hemodynamic improvement on acetazolamide-challenged single-photon emission computed tomography with 99mTc-hexamethylpropyleneamine oxime during the follow-up of 38.6 ± 36.7 months (range, 2.3-158.6 months). CONCLUSION: Low-flow bypass surgery showed acceptable treatment outcomes in the prevention of recurrent stroke.

Differences in health-related quality of life and somatic symptoms in employed and unemployed patients with epilepsy.

This study compared overall and specific aspects of health-related quality of life (HRQOL) and self-report of somatic, anxiety, and depressive symptoms between employed (n = 71) and unemployed (n = 48) patients with epilepsy (PWE). The Quality of Life in Epilepsy (QOLIE-89) and the Personality Assessment Inventory (PAI) were examined. The unemployed group reported significantly worse overall HRQOL including aspects of HRQOL related to epilepsy, physical health, mental health, and cognitive function. Among these four, physical health related HRQOL revealed the most difference between groups. While there were no differences between the groups in the level of social support and social isolation, the unemployed group reported worse social function with respect to work and driving. The unemployed group reported significantly greater somatic symptoms, but not anxiety and depressive symptoms. When specifically examining the subscales of the Somatic Concerns scale, conversion and health concerns, but not somatization, were greater in the unemployed group. Among the Depression subscales, the unemployed group reported greater physiologically manifested depressive symptoms. These findings suggest that along with optimizing seizure control, identifying and addressing presence of physical limitations, dysfunction, and somatic symptoms are also of importance in the care of PWE, particularly for those who are unemployed.

Reliability and Agreement Assessment of Sarcopenia Diagnosis through Comparison of Bioelectrical Impedance Analysis and Dual-Energy X-ray Absorptiometry.

A unified diagnostic criterion has yet to be established for sarcopenia. Therefore, we analyzed the reliability and validity of sarcopenia diagnosis using bioelectrical impedance analysis (BIA) compared with the gold standard, dual-energy X-ray absorptiometry (DEXA), and evaluated the predictive accuracy of BIA for diagnosis. The clinical trial, involving a total of 239 participants, was conducted between December 2018 and September 2019 on healthy volunteers without significant medical histories. The participants underwent health assessments, followed by sequential DEXA and BIA measurements. In both the low and normal appendicular skeletal muscle (ASM) groups, there were significant differences in the right arm, left arm, right leg, left leg, ASM, and ASM index (ASMI) between DEXA and BIA across all age groups (p < 0.05). BIA tended to overestimate compared to DEXA, but ASMI values for males and females were consistent with the criteria for sarcopenia. Bland-Altman analysis showed that each segment in both the low and normal ASM groups fell within the limits of agreement (LOA). The diagnosis of sarcopenia using BIA was significantly different from that using DEXA. However, it exhibited a significantly high correlation, fell within the LOA, and demonstrated high predictive accuracy. BIA can be considered an effective tool for diagnosing sarcopenia.

Safety assessments of recombinant DTaP vaccines developed in South Korea.

Purpose: Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore, inactivated acellular pertussis (aP) vaccines and genetically detoxified recombinant pertussis (rP) vaccines are being developed. The aim of this study was to assess the safety profile of a novel rP vaccine under development in comparison to commercial diphtheria-tetanus-acellular pertussis (DTaP) vaccines. Materials and Methods: The two positive control DTaP vaccines (two- and tri-components aP vaccines) and two experimental recombinant DTaP (rDTaP) vaccine (two- and tri-components aP vaccines adsorbed to either aluminum hydroxide or purified oat beta-glucan) were used. Temperature histamine sensitization test (HIST), indirect Chinese hamster ovary (CHO) cell cluster assay, mouse-weight-gain (MWG) test, leukocytosis promoting (LP) test, and intramuscular inflammatory cytokine assay of the injection site performed for safety assessments. Results: HIST results showed absence of residual pertussis toxin (PTx) in both control and experimental DTaP vaccine groups, whereas in groups immunized with tri-components vaccines, the experimental tri-components rDTaP absorbed to alum showed an ultra-small amount of 0.0066 IU/mL. CHO cell clustering was observed from 4 IU/mL in all groups. LP tests showed that neutrophils and lymphocytes were in the normal range in all groups immunized with the two components vaccine. However, in the tri-components control DTaP vaccine group, as well as two- and tri-components rDTaP with beta-glucan group, a higher monocyte count was observed 3 days after vaccination, although less than 2 times the normal range. In the MWG test, both groups showed changes less than 20% in body temperature and body weight before the after the final immunizations. Inflammatory cytokines within the muscle at the injection site on day 3 after intramuscular injection revealed no significant response in all groups. Conclusion: There were no findings associated with residual PTx, and no significant differences in both local and systemic adverse reactions in the novel rDTaP vaccine compared to existing available DTaP vaccines. The results suggest that the novel rDTaP vaccine is safe.

Comparison of three-dimensional printed resin crowns and preformed stainless steel crowns for primary molar restorations: a randomized controlled trial.

The importance of aesthetics in children has increased over time. Therefore, this multicenter randomized clinical trial aimed to analyze and compare three-dimensional (3D)-printed resin crowns (RCs) as a potential alternative to stainless-steel crowns (SSCs) for restoring primary molars with extensive carious lesions. According to the null hypothesis, no statistically significant difference was observed in restoration failure between RC and SSC groups. A total of 56 primary molars after pulp treatment at two dental hospitals were included. After pulp treatment, the teeth were randomly divided into two groups: SSCs (n = 28) and RCs (n = 28). At 1 week and 3, 6 and 12 months, the Quigley-Hein plaque index (QHI), gingival index (GI), occlusal wear, and survival rate were assessed by examination, radiography and alginate impressions. No significant difference in QHI was observed between the two groups. However, the GI at 12 months and occlusal wear in the RC group were significantly higher than those in the SSC group (p < 0.05). The survival rates were 100% in the SSC group and 82.1% in the RC group (p = 0.047). Cracks and discoloration were also observed in the RCs. Within the limitations of this study, 3D-printed RCs are aesthetically superior to SSCs and clinically easy to repair. However, if clinical effectiveness and safety are improved, RCs could potentially become a viable aesthetic alternative in the future.

Biodegradable Polymer Versus Polymer-Free Ultrathin Sirolimus-Eluting Stents: Analysis of the Stent Arm Registry From the HOST-IDEA Randomized Trial.

BACKGROUND: The efficacy and safety of each third-generation drug-eluting stent with ultrathin struts and advanced polymer technology remain unclear. We investigated the clinical outcomes of percutaneous coronary intervention using the Coroflex ISAR polymer-free sirolimus-eluting stent (SES) or Orsiro biodegradable polymer SES. METHODS: The HOST-IDEA trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Coronary Intervention With Next-Generation Drug-Eluting Stent Platforms and Abbreviated Dual Antiplatelet Therapy), initially designed with a 2×2 factorial approach, sought to randomize patients undergoing percutaneous coronary intervention based on dual antiplatelet therapy duration (3 versus 12 months) and stent type (Coroflex ISAR versus Orsiro). Despite randomizing 2013 patients for dual antiplatelet therapy duration, the stent arm transitioned to a registry format during the trial. Among these, 328 individuals (16.3%) were randomized for Coroflex ISAR or Orsiro SES, while 1685 (83.7%) underwent percutaneous coronary intervention without stent-type randomization. In this study, the Coroflex ISAR (n=559) and Orsiro groups (n=1449) were matched using a propensity score. The prespecified primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization at 12 months. RESULTS: The baseline patient and procedural characteristics were well balanced between the Coroflex ISAR and Orsiro groups after propensity score matching (n=559, each group). The Coroflex ISAR group was significantly associated with a higher rate of target lesion failure, mainly driven by clinically driven target lesion revascularization, compared with the Orsiro group (3.4% versus 1.1%; hazard ratio, 3.21 [95% CI, 1.28-8.05]; P=0.01). A higher risk of target lesion failure in the Coroflex ISAR group was consistently observed across various subgroups. The rates of any bleeding (hazard ratio, 0.85 [95% CI, 0.51-1.40]; P=0.52) and major bleeding (hazard ratio, 1.58 [95% CI, 0.61-4.08]; P=0.34) were comparable between the 2 groups. CONCLUSIONS: In this propensity score-matched analysis of the stent arm registry from the HOST-IDEA trial, the Orsiro SES was associated with significantly better outcomes in terms of 1-year target lesion failure, mainly driven by clinically driven target lesion revascularization, than the Coroflex ISAR SES. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02601157.

Tuberculous pleural effusion-induced Arg-1+ macrophage polarization contributes to lung cancer progression via autophagy signaling.

BACKGROUND: The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying mechanisms remain unclear, and the role of macrophage (MФ) polarization in cancer progression is unknown. The aim of the present study was to investigate the role of M2 Arg-1+ MФ in tuberculous pleurisy-assisted tumorigenicity in vitro and in vivo. METHODS: The interactions between tuberculous pleural effusion (TPE)-induced M2 Arg-1+ MФ and A549 lung cancer cells were evaluated. A murine model injected with cancer cells 2 weeks after Mycobacterium bovis bacillus Calmette-Guérin pleural infection was used to validate the involvement of tuberculous fibrosis to tumor invasion. RESULTS: Increased CXCL9 and CXCL10 levels of TPE induced M2 Arg-1+ MФ polarization of murine bone marrow-derived MФ. TPE-induced M2 Arg-1+ MФ polarization facilitated lung cancer proliferation via autophagy signaling and E-cadherin signaling in vitro. An inhibitor of arginase-1 targeting M2 Arg-1+ MФ both in vitro and in vivo significantly reduced tuberculous fibrosis-induced metastatic potential of lung cancer and decreased autophagy signaling and E-cadherin expression. CONCLUSION: Tuberculous pleural fibrosis induces M2 Arg-1+ polarization, and M2 Arg-1+ MФ contribute to lung cancer metastasis via autophagy and E-cadherin signaling. Therefore, M2 Arg-1+ tumor associated MФ may be a novel therapeutic target for tuberculous fibrosis-induced lung cancer progression.

Guidelines for Manufacturing and Application of Organoids: Kidney.

Recent advancements in organoid technology have led to a vigorous movement towards utilizing it as a substitute for animal experiments. Organoid technology offers versatile applications, particularly in toxicity testing of pharmaceuticals or chemical substances. However, for the practical use in toxicity testing, minimal guidance is required to ensure reliability and relevance. This paper aims to provide minimal guidelines for practical uses of kidney organoids derived from human pluripotent stem cells as a toxicity evaluation model in vitro.

Factors predicting redislocation or suture-break in eyes after scleral-fixated intraocular lens.

PURPOSE: To investigate predictive factors for redislocation in patients with recurrent intraocular lens (IOL) dislocation following secondary scleral-fixated IOL (SFIOL) surgery. SETTING: Two tertiary referral hospitals. DESIGN: Retrospective case series. METHODS: Patients undergoing SFIOL surgery were grouped into redislocation and no-redislocation groups. Medical records of consecutive patients who underwent SFIOL surgery between June 2014 and December 2019 at two tertiary referral centers were reviewed. Data regarding patient demographics, treatment factors, anatomical and functional outcomes, and postoperative complications were recorded. RESULTS: We included 237 eyes of 225 patients (169 [75.1%] men). The redislocation group was more likely to have a younger mean age at the initial SFIOL surgery (redislocation vs no-redislocation, 55.4 vs 62.0 years, respectively; P=0.008), have a prior history of a previous suture-break (23 eyes, 52.3% vs 1 eye, 0.5%; P<0.001), and have undergone the initial SFIOL surgery using <1 mm-sized side-port incisions (17 eyes, 38.6% vs 32 eyes, 16.5%; P=0.002) than was the no-redislocation group. Additionally, the redislocation group had a higher occurrence of complications (P<0.001). Multivariable regression revealed that younger age, left eye involvement, aphakic status prior to the surgery, unremarkable primary IOL dislocation cause, need for ocular hypertension treatment and glaucoma surgery, and no large incision during the initial surgery were significantly (all P<0.05) associated with redislocation. CONCLUSION: Younger age, left eye involvement, postoperative complications like ocular hypertension and glaucoma, and techniques without large incisions increase the risk of redislocation. Conversely, lower risk factors include unremarkable surgery causes and a history of aphakic conditions.

Effect of perioperative intravenous ibuprofen versus acetaminophen on postoperative opioid consumption and pain after general anesthesia: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

Background: Ibuprofen and acetaminophen are widely used as adjuvant analgesics for postoperative pain. This meta-analysis compared the effects of intravenous (IV) ibuprofen and acetaminophen on postoperative opioid consumption and pain intensity after general anesthesia. Methods: PubMed/MEDLINE, EMBASE, and Cochrane Library databases were searched to identify relevant studies published up to May 2023. Randomized controlled trials (RCTs) comparing the effects of perioperative IV ibuprofen and acetaminophen on postoperative opioid consumption and pain after general anesthesia were included in the meta-analysis and trial sequential analysis (TSA). Results: Eight studies with 494 participants were included. Compared to IV acetaminophen, IV ibuprofen significantly reduced 24 h opioid consumption, presented as morphine equivalents (mean difference [MD]: -6.01 mg, 95% CI [-8.60, -3.42], P < 0.00001, I2 = 55%), and pain scores (on a scale of 0-10) at 4-6 h (MD: -0.83, 95% CI [-1.29, -0.37], P = 0.0004, I2 = 65%) and 12 h (MD: -0.38, 95% CI [-0.68, -0.08], P = 0.01, I2 = 11%) postoperatively. These results were statistically significant in TSA. Pain scores at 24 h postoperatively and side effects were not significantly different between the two groups in the meta-analysis, and TSA revealed that the sample size was too small to adequately evaluate the effects, requiring further studies for conclusive results. Conclusions: Perioperative IV ibuprofen reduced 24 h opioid consumption and pain severity up to 12 h postoperatively compared to acetaminophen. Additional research is required to assess pain intensity beyond 12 h and side effects.

Prognostic potentials of AI in ophthalmology: systemic disease forecasting via retinal imaging.

BACKGROUND: Artificial intelligence (AI) that utilizes deep learning (DL) has potential for systemic disease prediction using retinal imaging. The retina's unique features enable non-invasive visualization of the central nervous system and microvascular circulation, aiding early detection and personalized treatment plans for personalized care. This review explores the value of retinal assessment, AI-based retinal biomarkers, and the importance of longitudinal prediction models in personalized care. MAIN TEXT: This narrative review extensively surveys the literature for relevant studies in PubMed and Google Scholar, investigating the application of AI-based retina biomarkers in predicting systemic diseases using retinal fundus photography. The study settings, sample sizes, utilized AI models and corresponding results were extracted and analysed. This review highlights the substantial potential of AI-based retinal biomarkers in predicting neurodegenerative, cardiovascular, and chronic kidney diseases. Notably, DL algorithms have demonstrated effectiveness in identifying retinal image features associated with cognitive decline, dementia, Parkinson's disease, and cardiovascular risk factors. Furthermore, longitudinal prediction models leveraging retinal images have shown potential in continuous disease risk assessment and early detection. AI-based retinal biomarkers are non-invasive, accurate, and efficient for disease forecasting and personalized care. CONCLUSION: AI-based retinal imaging hold promise in transforming primary care and systemic disease management. Together, the retina's unique features and the power of AI enable early detection, risk stratification, and help revolutionizing disease management plans. However, to fully realize the potential of AI in this domain, further research and validation in real-world settings are essential.

A deep catalogue of protein-coding variation in 983,578 individuals.

Rare coding variants that significantly impact function provide insights into the biology of a gene1-3. However, ascertaining their frequency requires large sample sizes4-8. Here, we present a catalogue of human protein-coding variation, derived from exome sequencing of 983,578 individuals across diverse populations. 23% of the Regeneron Genetics Center Million Exome data (RGC-ME) comes from non-European individuals of African, East Asian, Indigenous American, Middle Eastern, and South Asian ancestry. This catalogue includes over 10.4 million missense and 1.1 million predicted loss-of-function (pLOF) variants. We identify individuals with rare biallelic pLOF variants in 4,848 genes, 1,751 of which have not been previously reported. From precise quantitative estimates of selection against heterozygous loss-of-function, we identify 3,988 loss-of-function intolerant genes, including 86 that were previously assessed as tolerant and 1,153 lacking established disease annotation. We also define regions of missense depletion at high resolution. Notably, 1,482 genes have regions depleted of missense variants despite being tolerant to pLOF variants. Finally, we estimate that 3% of individuals have a clinically actionable genetic variant, and that 11,773 variants reported in ClinVar with unknown significance are likely to be deleterious cryptic splice sites. To facilitate variant interpretation and genetics-informed precision medicine, we make this important resource of coding variation from the RGC-ME accessible via a public variant allele frequency browser.

Epidural, Inadvertent Subdural, and Combined Epidural-Subdural Anesthesia in Lumbar Spine Surgery: A Retrospective Analysis.

This study aimed to categorize contrast media images associated with epidural, subdural, and combined epidural-subdural anesthesia in patients who had undergone fluoroscopy-guided epidural anesthesia using contrast media combined with monitored anesthesia care (MAC) targeted at deep sedation, incorporating capnography over 5 years. Additionally, a correlation was established between the anesthetic effects and radiographic findings according to the categorized imaging appearances. This study included 628 patients who underwent endoscopic, open, or fusion surgery under epidural anesthesia at Nanoori Hospital in Gangnam between March 2018 and September 2023. Fluoroscopy-guided epidural anesthesia using contrast media combined with MAC and capnography was used. The dataset included detailed radiographic imaging, nursing, and anesthesia records. Distinct patterns of anesthesia administration were observed, with 49%, 19.6%, and 31% of patients receiving epidural, subdural, and combined epidural-subdural anesthesia, respectively. The incidence and duration of motor block were significantly different among the three groups. Additionally, subdural anesthesia displayed a higher incidence of motor block and a prolonged motor deficit duration than epidural anesthesia. Fluoroscopic guidance using a contrast medium for epidural and subdural anesthesia ensures precise space identification and prevents serious anesthetic complications. Our findings suggest the potential to achieve stable anesthesia, particularly using subdural and combined epidural-subdural anesthesia.

Stabilizing the Catalyst Layer for Durable and High Performance Alkaline Membrane Fuel Cells and Water Electrolyzers.

Anion exchange membrane (AEM) fuel cells (AEMFCs) and water electrolyzers (AEMWEs) suffer from insufficient performance and durability compared with commercialized energy conversion systems. Great efforts have been devoted to designing high-quality AEMs and catalysts. However, the significance of the stability of the catalyst layer has been largely disregarded. Here, an in situ cross-linking strategy was developed to promote the interactions within the catalyst layer and the interactions between catalyst layer and AEM. The adhesion strength of the catalyst layer after cross-linking was improved 7 times compared with the uncross-linked catalyst layer due to the formation of covalent bonds between the catalyst layer and AEM. The AEMFC can be operated under 0.6 A cm-2 for 1000 h with a voltage decay rate of 20 µV h-1. The related AEMWE achieved an unprecedented current density of 15.17 A cm-2 at 2.0 V and was operated at 0.5, 1.0, and 1.5 A cm-2 for 1000 h.

Empowering pancreatic tumor homing with augmented anti-tumor potency of CXCR2-tethered CAR-NK cells.

Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells are a promising immunotherapy for solid cancers; however, their effectiveness against pancreatic cancer is limited by the immunosuppressive tumor microenvironment. In particular, low NK cell infiltration poses a major obstacle that reduces cytotoxicity. The current study aimed to enhance the tumor-homing capacity of CAR-NK cells by targeting the chemokine-chemokine receptor axis between NK and pancreatic cancer cells. To this end, data from a chemokine array and The Cancer Genome Atlas pan-cancer cohort were analyzed. Pancreatic cancer cells were found to secrete high levels of ligands for C-X-C motif receptor 1 (CXCR1) and CXCR2. Subsequently, we generated anti-mesothelin CAR-NK cells incorporating CXCR1 or CXCR2 and evaluated their tumor-killing abilities in 2D cancer cell co-culture and 3D tumor-mimetic organoid models. CAR-NK cells engineered with CXCR2 demonstrated enhanced tumor killing and strong infiltration of tumor sites. Collectively, these findings highlight the potential of CXCR2-augmented CAR-NK cells as a clinically relevant modality for effective pancreatic cancer treatment. By improving their infiltration and tumor-killing capabilities, these CXCR2-augmented CAR-NK cells have the potential to overcome the challenges posed by the immunosuppressive tumor microenvironment, providing improved therapeutic outcomes.

Prognostic Significance of Bulky Nodal Disease in Anal Cancer Management: A Multi Institutional Study.

Purpose: This study aimed to assess the prognostic significance of bulky nodal involvement in patients with anal squamous cell carcinoma treated with definitive chemoradiotherapy. Materials and Methods: We retrospectively analyzed medical records of patients diagnosed with anal squamous cell carcinoma who underwent definitive chemoradiotherapy at three medical centers between 2004 and 2021. Exclusion criteria included distant metastasis at diagnosis, 2D radiotherapy, and salvage treatment for local relapse. Bulky N+ was defined as nodes with a long diameter of 2 cm or greater. Results: A total of 104 patients were included, comprising 51 with N0, 46 with non-bulky N+, and 7 with bulky N+. The median follow-up duration was 54.0 months (range, 6.4-162.2 months). Estimated 5-year progression-free survival (PFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS) rates for patients with bulky N+ were 42.9%, 42.9%, and 47.6%, respectively. Bulky N+ was significantly associated with inferior PFS, LRRFS and OS compared to patients without or with non-bulky N+, even after multivariate analysis. We proposed a new staging system incorporating bulky N+ as N2 stage, with estimated 5-year LRRFS, PFS, and OS rates of 81.1%, 80.6%, and 86.2% for stage I, 67.7%, 60.9%, and 93.3% for stage II, and 42.9%, 42.9%, and 47.6% for stage III disease, enhancing the predictability of prognosis. Conclusion: Patients with bulky nodal disease treated with standard chemoradiotherapy experienced poor survival outcomes, indicating the potential necessity for further treatment intensification.

Genotoxicity and safety pharmacology of the rVSVInd(GML)-mspSGtc vaccine against SARS-CoV-2 in Sprague-Dawley rats and Beagle dogs.

The emergence of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a pandemic, prompting rapid vaccine development. Although vaccines are effective, the occurrence of rare adverse events following vaccination highlights the necessity of determining whether the benefits outweigh the risks posed by the infection itself. The recombinant Vesicular Stomatitis Virus (rVSV) platform is a promising vector for vaccines against emerging viruses. However, limited studies have evaluated the genotoxicity and safety pharmacology of this viral vector vaccine, which is crucial to ensure the safety of vaccines developed using this platform. Hence, the present study aimed to assess the genotoxicity and safety pharmacology of the rVSVInd(GML)-mspSGtc COVID-19 vaccine using micronucleus and comet assays, as well as neurobehavioral, body temperature, respiratory, and cardiovascular assessments in Sprague-Dawley rats and beagle dogs. The intramuscular administration of rVSVInd(GML)-mspSGtc at doses up to 1.5 × 109 PFU/animal did not increase the number of bone marrow micronucleated polychromatic erythrocytes or cause liver DNA damage. Additionally, it had no significant impact on neurobehavioral functions in rats and showed marginal temporary changes in body temperature, respiratory rate, heart rate, and electrocardiogram parameters in rats and dogs, all of which resolved within 24 h. Overall, following genotoxicity and pharmacological safety assessments, rVSVInd(GML)-mspSGtc displayed no notable systemic adverse effects in rats and dogs, suggesting its potential as a vaccine candidate for human clinical trials.

Clinical approaches for poststroke seizure: a review.

Poststroke seizure is a potential complication of stroke, which is the most frequent acute symptomatic seizure in adults. Patients with stroke may present with an abnormal or aggressive behavior accompanied by altered mental status and symptoms, such as hemiparesis, dysarthria, and sensory deficits. Although stroke manifestations that mimic seizures are rare, diagnosing poststroke seizures can be challenging when accompanied with negative postictal symptoms. Differential diagnoses of poststroke seizures include movement disorders, syncope, and functional (nonepileptic) seizures, which may present with symptoms similar to seizures. Furthermore, it is important to determine whether poststroke seizures occur early or late. Seizures occurring within and after 7 d of stroke onset were classified as early and late seizures, respectively. Early seizures have the same clinical course as acute symptomatic seizures; they rarely recur or require long-term antiseizure medication. Conversely, late seizures are associated with a risk of recurrence similar to that of unprovoked seizures in a patient with a focal lesion, thereby requiring long-term administration of antiseizure medication. After diagnosis, concerns regarding treatment strategies, treatment duration, and administration of primary and secondary prophylaxis often arise. Antiseizure medication decisions for the initiation of short-term primary and long-term secondary seizure prophylaxis should be considered for patients with stroke. Antiseizure drugs such as lamotrigine, carbamazepine, lacosamide, levetiracetam, phenytoin, and valproate may be administered. Poststroke seizures should be diagnosed systematically through history with differential diagnosis; in addition, classifying them as early or late seizures can help to determine treatment strategies.

Determinants of the happiness of adolescents: A leisure perspective.

Leisure plays a key role in the happiness of youth. Studies have shown that various factors of leisure, such as the type, the time, the cost, and the space, have an influence on the adolescents' happiness. However, little is known about which of these factors is a major factor in youth's happiness. The purpose of this study is to explore the leisure factors that determine happiness in adolescents by examining the relationship between happiness and various leisure factors. The study used the method of machine learning to analyze national statistical data, National Leisure Activity Survey. The data used in this study were from the National Leisure Activity Survey 2019, which is a national statistic produced by the Ministry of Culture, Sports and Tourism in the Republic of Korea. The analysis found that leisure perceptions, academic and leisure balance, and public leisure space have a very important impact on the adolescents' well-being. The findings of this research may contribute to a better understanding of leisure and happiness in adolescents, and will also help adolescents make better use of their leisure time, leading to better leisure lives, and ultimately contribute to raising their level of happiness.