Comparative efficacy of biologics for patients with inadequately controlled asthma: A network meta-analysis.

Background: Few studies have evaluated the comparative efficacy of biologics for asthma. This network meta-analysis aimed to compare the efficacy of biologics. Methods: This study included randomized controlled trials (RCTs) evaluating the efficacy of a biologic compared to a placebo or another biologic in patients with inadequately controlled asthma despite high-intensity treatment, published by January 6, 2022. Two researchers independently searched the PubMed, Embase, Web of Science, and Scopus and assessed the risk of bias using the Cochrane tool. The outcomes of interest were the annual asthma exacerbation rate (AER), forced expiratory volume per second before bronchodilator use (preBD FEV1), the asthma control questionnaire (ACQ), and asthma quality of life questionnaire (AQLQ) results. A frequentist network meta-analysis was conducted, and a random effects model was used to draw pooled incidence rate ratio or standardized mean differences. Results: Twenty-three RCTs with 8376 participants were retrieved. All biologics included in this study were associated with significantly better effects than placebo in AER, preBD FEV1, and ACQ outcomes. Although there were no significant differences between the biologics in the overall study population, patients with eosinophil levels ≥300 cells/µL or eosinophilic asthma showed that dupilumab and tezepelumab were significantly better than anti-IL-5 biologics in improving preBD FEV1. Additionally, in patients with eosinophil levels ≥300 cells/µL, benralizumab, unlike reslizumab, performed significantly better than placebo in improving ACQ and AQLQ outcomes. Conclusion: The comparative effects of biologics can be considered with phenotypes and biomarkers to help clinicians select an appropriate treatment for inadequately controlled asthma.

Performance of ChatGPT on Solving Orthopedic Board-Style Questions: A Comparative Analysis of ChatGPT 3.5 and ChatGPT 4.

Background: The application of artificial intelligence and large language models in the medical field requires an evaluation of their accuracy in providing medical information. This study aimed to assess the performance of Chat Generative Pre-trained Transformer (ChatGPT) models 3.5 and 4 in solving orthopedic board-style questions. Methods: A total of 160 text-only questions from the Orthopedic Surgery Department at Seoul National University Hospital, conforming to the format of the Korean Orthopedic Association board certification examinations, were input into the ChatGPT 3.5 and ChatGPT 4 programs. The questions were divided into 11 subcategories. The accuracy rates of the initial answers provided by Chat GPT 3.5 and ChatGPT 4 were analyzed. In addition, inconsistency rates of answers were evaluated by regenerating the responses. Results: ChatGPT 3.5 answered 37.5% of the questions correctly, while ChatGPT 4 showed an accuracy rate of 60.0% (p < 0.001). ChatGPT 4 demonstrated superior performance across most subcategories, except for the tumor-related questions. The rates of inconsistency in answers were 47.5% for ChatGPT 3.5 and 9.4% for ChatGPT 4. Conclusions: ChatGPT 4 showed the ability to pass orthopedic board-style examinations, outperforming ChatGPT 3.5 in accuracy rate. However, inconsistencies in response generation and instances of incorrect answers with misleading explanations require caution when applying ChatGPT in clinical settings or for educational purposes.

Comparison of Midterm Outcomes between All-Inside Arthroscopic and Open Modified Broström Procedures as Treatment for Chronic Ankle Instability.

Background: Although the all-inside arthroscopic modified Broström operation (AMBO) and open modified Broström operation (OMBO) for chronic lateral ankle instability (CLAI) showed favorable outcomes up to 1-year short-term follow-up, concerns about the long-term stability of AMBO are still present. Therefore, we aimed to compare midterm outcomes between the 2 methods by extending the observation period. Methods: Fifty-four patients undergoing ankle surgery between August 2013 and July 2017 were included in the AMBO (n = 37) and OMBO (n = 17) groups. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale and a visual analog scale (VAS) were used to evaluate the clinical outcomes. Anterior drawer test and talar tilt angle were used to evaluate the radiological outcomes. The mean follow-up duration was 59.69 months. Results: The 2 groups both showed improved clinical and radiological results statistically. In addition, they did not differ in age, sex, or preoperative AOFAS ankle-hindfoot scale score, VAS score, anterior drawer test, or talar tilt angle. No significant difference in the final follow-up postoperative clinical scores or radiological outcomes was observed. Conclusions: AMBO and OMBO as treatments for CLAI did not yield differing clinical or radiological outcomes at a mean follow-up time point of 59.69 months.

Low Absolute Lymphocyte Count Correlates with Lymph Node Metastases and Worse Survival of Patients with Gastric Cancer.

BACKGROUND: Several studies have found that the absolute lymphocyte (ALC) or neutrophil count predicts the survival of patients with solid tumors, and that the neutrophil-to-lymphocyte ratio and the prognostic nutritional index are useful markers of gastric cancer prognosis. However, it remains unclear whether the ALC is prognostic of lymph node (LN) metastasis in patients with gastric cancer. In this study, we aimed to explore the impact of ALC on prognosis and distinctive clinical characteristics in patients with gastric cancer. PATIENTS AND METHODS: The medical records of patients with gastric adenocarcinomas who underwent radical gastrectomy with curative intent at Seoul St. Mary's Hospital and Yeouido St. Mary's Hospital between January 2010 and December 2017 were reviewed. Of these, 4149 patients for whom preoperative white blood cell, neutrophil, and lymphocyte counts were available were enrolled. RESULTS: In all 4149 patients, ALC gradually decreased as the pN stage increased. Those with an ALC of less than 1360 cells/µL were defined as a low-ALC group, and advanced cT and cN stages were the strongest risk factors for LN metastasis in both univariate and multivariate analyses; undifferentiated tumor histology and a low ALC were also significant risk factors. Patients of all stages in the ALC-low group exhibited poorer prognoses. The ALC-low group also exhibited a higher recurrence rate in a greater proportion of LNs. CONCLUSIONS: In patients with gastric cancer, as the preoperative ALC decreases, the incidence of LN metastasis increases. A low ALC is associated with a high recurrence rate, particularly in LNs.

High-efficiency thermo-optic control of a longitudinal radiation angle in a silicon-based optical phased array by leveraging the backside air trench structure.

We proposed a 2D 1 × 64 silicon optical phased array with a backside silicon-etched structure to achieve high tuning efficiency and a wide longitudinal steering range. At the radiator array, the n-i-n heater was implemented to steer the light in a longitudinal direction through the thermo-optic effect. The deep reactive ion etching process was utilized to generate the 600 µm depth air trench with a 1.8 cm2 area from the backside of the radiator array. We achieved almost 100% increment in terms of tuning efficiency, which is 1.56°/W for the proposed structure and 0.78°/W for the conventional structure.

Development of a fit-for-purpose multi-marker panel for early diagnosis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) suffers from 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 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 analytical robustness of proposed biomarkers which is critical for transitioning from research-grade to clinical-grade assays. Moreover, throughput and cost-effectiveness of proposed assays ought to be considered concomitantly from 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 discovery phase, we comprehensively surveyed putative PDAC biomarkers from both in-house data and prior studies. In 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 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.

Removal of circulating mitochondrial N-formyl peptides via immobilized antibody therapy restores sepsis-induced neutrophil dysfunction.

During recovery from septic shock, circulating mitochondrial N-formyl peptides (mtFPs) predispose to secondary infection by occupying formyl peptide receptor 1 (FPR1) on the neutrophil (polymorphonuclear leukocyte, PMN) membrane, suppressing cytosolic calcium ([Ca2+]i)-dependent responses to secondarily encountered bacteria. However, no study has yet investigated therapeutic clearance of circulating mtFPs in clinical settings. Thus, we studied how to remove mtFPs from septic-shock plasma and whether such removal could preserve cell-surface FPR1 and restore sepsis-induced PMN dysfunction by normalizing [Ca2+]i flux. In in vitro model systems, mtFP removal rescued PMN FPR1-mediated [Ca2+]i flux and chemotaxis that had been suppressed by prior mtFP exposure. However, PMN functional recovery occurred in a stepwise fashion over 30 - 90 minutes. Intracellular Ca2+-calmodulin appears to contribute to this delay. In ex vivo model systems using blood samples obtained from patients with septic shock, anti-mtFP antibodies alone failed to eliminate mtFPs from septic-shock plasma or inhibit mtFP activity. We therefore created a beads-based anti-mtFP antibody cocktail (bb-AMfpA) by combining protein A/sepharose with antibodies specific for the most potent human mtFP chemoattractants. The bb-AMfpA treatment successfully removed those active mtFPs from septic-shock plasma. Furthermore, the bb-AMfpA treatment significantly restored chemotactic and bactericidal dysfunction of PMNs obtained from patients with septic shock who developed secondary infections. By clearing circulating mtFPs, the immobilized anti-mtFP antibody therapy prevented mtFP interactions with surface FPR1, thereby restoring [Ca2+]i-dependent PMN antimicrobial function in clinical septic-shock environments. This approach may help prevent the development of secondary, nosocomial infections in patients recovering from septic shock.

Serum cortisol and neuroticism for post-traumatic stress disorder over 2 years in patients with physical injuries.

AIM: This study aimed to explore the relationships between serum cortisol levels, personality traits, and the development of Post-Traumatic Stress Disorder (PTSD) over 2 years among individuals with physical injuries. METHODS: Participants were consecutively recruited from a trauma center and followed prospectively for 2 years. At baseline, serum cortisol levels were measured, and personality traits were categorized into five dimensions (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness), using the Big Five Inventory-10. The diagnosis of PTSD during follow-up (at 3, 6, 12, and 24 months post-injury) was determined using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were conducted to examine the interactions between cortisol levels, personality traits, and PTSD development. RESULTS: Among 923 patients analyzed, 112 (12.1%) were diagnosed with PTSD at some point during the study period, with prevalence rates decreasing from 8.8% at 3 months to 3.7% at 24 months post-injury. Direct associations between cortisol levels or personality traits and PTSD were not observed. However, a significant interaction between lower cortisol levels and higher Neuroticism in relation to PTSD risk was identified, especially during the early follow-up periods (3 to 6 months), but this association waned from the 12-month follow-up onward. CONCLUSION: Our findings reveal Neuroticism-dependent associations between serum cortisol levels and PTSD development, exhibiting temporal variations. These results suggest that PTSD development may be influenced by a complex, time-sensitive interplay of biological and psychosocial factors, underscoring the importance of considering individual differences in stress reactivity and personality in PTSD research and treatment.

Efficacy and Safety of Lurasidone vs. Quetiapine XR in Acutely Psychotic Patients With Schizophrenia in Korea: A Randomized, Double-Blind, Active-Controlled Trial.

OBJECTIVE: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. METHODS: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. RESULTS: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35-4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. CONCLUSION: Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Adiponectin prevents skin inflammation in rosacea by suppressing S6 phosphorylation in keratinocytes.

Numerous recent evidence highlights epidemiological connections between rosacea and metabolic disorders. However, the precise path through which metabolic factors impact rosacea risk is still unclear. Therefore, this study aims to investigate the role of adiponectin, a crucial adipokine that regulates metabolic homeostasis, in the pathogenesis of rosacea. We elucidated a detrimental feedback loop between rosacea-like skin inflammation and decreased levels of skin adiponectin. To elaborate, rosacea lesional skin exhibits diminished adiponectin expression compared to non-lesional areas in the same patients. Induction of rosacea-like inflammation reduced adiponectin levels in the skin by generating inflammatory cytokines that suppress adiponectin production from subcutaneous adipocytes. Conversely, complete depletion of adiponectin exacerbated rosacea-like features in the mouse model. Mechanistically, adiponectin deficiency led to heightened S6 phosphorylation, a marker of the mTORC1 signaling pathway, in the epidermis. Adiponectin significantly inhibited S6 phosphorylation in cultured keratinocytes. Notably, replenishing adiponectin whole protein or topically applying an agonist for adiponectin receptor 1 successfully improved rosacea-like features in mice. This study contributes to understanding the role of adiponectin in skin inflammation associated with rosacea pathophysiology, suggesting that restoring adiponectin function in the skin could be a potential therapeutic strategy.

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.

Acute and chronic effects of the antifouling booster biocide Irgarol 1051 on the water flea Moina macrocopa revealed by multi-biomarker determination.

Irgarol 1051 is an herbicide extensively utilized in antifouling paint due to its ability to inhibit photosynthesis. Irgarol and its photodegradation products are highly persistent in waters and sediments, although they are present in low concentrations. However, our understanding of the harmful effects of Irgarol on non-target organisms remains limited. In this study, we assessed the effects of acute (24 h) and chronic (14 days across three generations) exposure to different concentrations (including the 1/10 NOEC, NOEC, and 1/10 LC50 calculated from the 24-h acute toxicity test) of Irgarol using the water flea Moina macrocopa. Acute exposure to 1/10 LC50 significantly decreased survival, feeding rate, thoracic limb activity, heart rate, and acetylcholinesterase activity. Elevated levels of intracellular reactive oxygen species and malondialdehyde, along with a significant increase in catalase and superoxide dismutase activity, suggested the induction of oxidative stress in response to 1/10 LC50. An initial boost in glutathione level and the enzymatic activities of glutathione peroxidase and glutathione reductase, followed by a plunge, implies some compromise in the antioxidant defense system. Upon chronic exposure to the NOEC value, both generations F1 and F2 displayed a significant decrease in survival rate, body length, number of neonates per brood, and delayed sexual maturation, suggesting maternal transfer of potential damage through generations. Taken together, Irgarol induced acute toxicity through physiological and cholinergic damage, accompanied by the induction of oxidative stress, in the water flea. Even its sub-lethal concentrations can induce detrimental effects across generations when consistently exposed.

PPM1G dephosphorylates eIF4E in control of mRNA translation and cell proliferation.

The mRNA 5'cap-binding eukaryotic translation initiation factor 4E (eIF4E) plays a critical role in the control of mRNA translation in health and disease. One mechanism of regulation of eIF4E activity is via phosphorylation of eIF4E by MNK kinases, which promotes the translation of a subset of mRNAs encoding pro-tumorigenic proteins. Work on eIF4E phosphatases has been paltry. Here, we show that PPM1G is the phosphatase that dephosphorylates eIF4E. We describe the eIF4E-binding motif in PPM1G that is similar to 4E-binding proteins (4E-BPs). We demonstrate that PPM1G inhibits cell proliferation by targeting phospho-eIF4E-dependent mRNA translation.

Airway and Airway Obstruction Site Segmentation Study Using U-Net with Drug-Induced Sleep Endoscopy Images.

Obstructive sleep apnea is characterized by a decrease or cessation of breathing due to repetitive closure of the upper airway during sleep, leading to a decrease in blood oxygen saturation. In this study, employing a U-Net model, we utilized drug-induced sleep endoscopy images to segment the major causes of airway obstruction, including the epiglottis, oropharynx lateral walls, and tongue base. The evaluation metrics included sensitivity, specificity, accuracy, and Dice score, with airway sensitivity at 0.93 (± 0.06), specificity at 0.96 (± 0.01), accuracy at 0.95 (± 0.01), and Dice score at 0.84 (± 0.03), indicating overall high performance. The results indicate the potential for artificial intelligence (AI)-driven automatic interpretation of sleep disorder diagnosis, with implications for standardizing medical procedures and improving healthcare services. The study suggests that advancements in AI technology hold promise for enhancing diagnostic accuracy and treatment efficacy in sleep and respiratory disorders, fostering competitiveness in the medical AI market.

The optimal measurement method considering reliability and validity in the anterior knee laxity of anterior cruciate ligament tears.

INTRODUCTION: To seek an optimal measurement method with high reliability and high validity for evaluation of the anterior knee laxity on stress radiographs and comparing the translation values to those of KT-2000 arthrometer. METHODS: Anterior knee laxity in 77 patients was measured preoperatively using the TelosTM and the KT-2000 arthrometer. Side-to-side difference measurements were taken using three conventional measuring methods and one proposed method (Modified Lateral). The knee position on the stress radiograph was evaluated and scored based on the stress radiograph qualifying criteria depending on stress film correctiveness. Intraclass correlation coefficients were analyzed to evaluate the reliability of the measurement methods and were compared between high (Group H) and low (Group L) radiograph quality score groups for each method. Validity was assessed by comparing the KT-2000 and the TelosTM using Pearson correlation (r value). RESULTS: The Modified Lateral method showed the best Intraclass Correlation Coefficients (ICCs), followed by Center to Center, and Medial to Medial and Lateral to Lateral methods without considering the quality of Telos. In the comparison between groups based on Telos quality for intra-rater reliability, the Medial to Medial (MM) method demonstrated the best reliability in both groups (MM: ICCs, Group H = 0.942, Group L = 0.917, P = 0.693). As for inter-rater reliability, the Modified Lateral (ML) method exhibited the best reliability in both groups (ML: ICCs, Group H = 0.923, Group L = 0.882, P = 0.547). The value measured using the ML method in Telos showed the highest correlation coefficient with the KT-2000 measured value in both groups H and L. There were no statistically significant differences among the correlation coefficient values. CONCLUSION: The Modified Lateral method is recommended for its high reliability, taking into account the differences in bilateral knee positions and anatomical discriminability on stress radiographs when evaluating anterior knee translation with Telos. It also best reflected the KT-2000 arthrometer. LEVEL OF EVIDENCE: Case Series, Level IV.

Gestating sows with a restricted feed allowance require a longer adaptation period before collecting feces compared with lactating sows in total tract digestibility assessments using index method.

The objective of the present experiment was to determine the minimum adaptation period for total tract digestibility experiments in gestating and lactating sows using the indigestible index method. Five gestating and 5 lactating sows at parities 3 to 5 were used. An indigestible index of 0.5% chromic oxide was supplemented to a diet based on corn and soybean meal. The daily feed allowance for gestating sows was 2 kg and 2 equal meals were provided to the sows. Lactating sows were fed 6 kg of feed per day in 3 equal meals. After feeding a diet without supplemental chromic oxide for 5 d, index-supplemented diets were provided to the gestating and lactating sows. Feces were collected at 24-h intervals for 9 and 7 d from gestating and lactating sows, respectively. Fecal Cr concentrations increased linearly (P < 0.001) and quadratically (P < 0.001) with collection time in both gestating and lactating sows. Minimum adaptation periods were estimated by one-slope broken-line model. The break point of Cr concentrations in feces was day 7.2 (SE = 0.3) in the gestating sows and day 4.2 (SE = 0.2) in the lactating sows, respectively. Apparent total tract digestibility of dry matter, organic matter, and energy on day 4 was less (P < 0.001) than that on days 8 to 9 in gestating sows fed the experimental diet with a 2-kg feed allowance. In lactating sows fed the experimental diets with a 6-kg feed allowance, the apparent total tract digestibility of dry matter, organic matter, and energy on day 3 was less (P < 0.05) than that on days 5 to 7. In conclusion, at least 8 d of adaptation period are required for gestating sows to determine total tract digestibility using Cr as the indigestible index method whereas 5 d of adaptation period are required for lactating sows. An insufficient adaptation period results in lower digestibility values.

Nutrient digestibility of feed ingredients fed to pigs has been often determined using indigestible index method that requires an accurate determination of index content in the feed and feces. A reduced feed allowance for gestating sows results in longer retention in the digestive tract, requiring a longer adaptation period to achieve stable fecal index values. Thus, this experiment aimed to determine the minimum adaptation period required for total tract digestibility experiments using the index method in gestating and lactating sows. In this experiment, at least 8 d of adaptation period were required before fecal grab sampling for the determination of nutrient digestibility using indigestible index in gestating sows fed 2 kg of feed per day whereas at least 5 d of adaptation period was required before fecal grab sampling in lactating sows fed with 6 kg of feed per day. Additionally, insufficient adaptation periods resulted in reduced calculated values for total tract digestibility of energy and nutrients in both gestating and lactating sows.

Impact of AI-assisted CXR analysis in detecting incidental lung nodules and lung cancers in non-respiratory outpatient clinics.

Purpose: The use of artificial intelligence (AI) for chest X-ray (CXR) analysis is becoming increasingly prevalent in medical environments. This study aimed to determine whether AI in CXR can unexpectedly detect lung nodule detection and influence patient diagnosis and management in non-respiratory outpatient clinics. Methods: In this retrospective study, patients over 18 years of age, who underwent CXR at Yongin Severance Hospital outpatient clinics between March 2021 and January 2023 and were identified to have lung nodules through AI software, were included. Commercially available AI-based lesion detection software (Lunit INSIGHT CXR) was used to detect lung nodules. Results: Out Of 56,802 radiographic procedures, 40,191 were from non-respiratory departments, with AI detecting lung nodules in 1,754 cases (4.4%). Excluding 139 patients with known lung lesions, 1,615 patients were included in the final analysis. Out of these, 30.7% (495/1,615) underwent respiratory consultation and 31.7% underwent chest CT scans (512/1,615). As a result of the CT scans, 71.5% (366 cases) were found to have true nodules. Among these, the final diagnoses included 36 lung cancers (7.0%, 36/512), 141 lung nodules requiring follow-up (27.5%, 141/512), 114 active pulmonary infections (22.3%, 114/512), and 75 old inflammatory sequelae (14.6%, 75/512). The mean AI nodule score for lung cancer was significantly higher than that for other nodules (56.72 vs. 33.44, p < 0.001). Additionally, active pulmonary infection had a higher consolidation score, and old inflammatory sequelae had the highest fibrosis score, demonstrating differences in the AI analysis among the final diagnosis groups. Conclusion: This study indicates that AI-detected incidental nodule abnormalities on CXR in non-respiratory outpatient clinics result in a substantial number of clinically significant diagnoses, emphasizing AI's role in detecting lung nodules and need for further evaluation and specialist consultation for proper diagnosis and management.

Primary treatments for solitary hepatocellular carcinoma ≤ 3 cm: A systematic review and network meta-analysis.

Various treatment modalities are available for small solitary hepatocellular carcinoma (HCC), yet the optimal primary treatment strategy for tumors ≤ 3 cm remains unclear. This network meta-analysis investigates the comparative efficacy of various interventions on the long-term outcomes of patients with solitary HCC ≤ 3 cm. A systematic search of electronic databases from January 2000 to December 2023 was conducted to identify studies that compared at least two of the following treatments: surgical resection (SR), radiofrequency ablation (RFA), microwave ablation (MWA), and transarterial chemoembolization (TACE). Survival data were extracted, and pooled hazard ratios with 95% confidence intervals were calculated using a frequentist network meta-analysis. A total of 30 studies, comprising 2 randomized controlled trials and 28 retrospective studies, involving 8,053 patients were analyzed. Surgical resection showed the highest overall survival benefit with a p-score of 0.95, followed by RFA at 0.59, MWA at 0.23, and TACE, also at 0.23. Moreover, SR provided the most significant recurrence-free survival advantage, with a p-score of 0.95, followed by RFA at 0.31 and MWA at 0.19. Sensitivity analyses, excluding low-quality or retrospective non-matched studies, corroborated these findings. This network meta-analysis demonstrates that SR is the most effective first-line curative treatment for single HCC ≤ 3 cm, followed by RFA in patients with preserved liver function. The limited data on MWA and TACE underscore the need for further studies.

Function of a complex of p-Y42 RhoA GTPase and pyruvate kinase M2 in EGF signaling pathway in glioma cells.

Epidermal growth factor (EGF) is known to be a critical stimulant for inducing the proliferation of glioma cancer cells. In our study, we observed that GST-RhoA binds to pyruvate kinase M2 (PKM2) in vitro. While EGF reduced the levels of RhoA protein, it significantly increased p-Y42 RhoA, as well as PKM1 and PKM2 in LN18 glioma cell line. We determined that RhoA undergoes degradation through ubiquitination involving SCF1 and Smurf1. Interestingly, we observed that p-Y42 RhoA binds to PKM2, while the dephosphomimetic form, RhoA Y42F, did not. Additionally, our observation revealed that PKM2 stabilized both RhoA and p-Y42 RhoA. Importantly, RhoA, p-Y42 RhoA, and PKM2, but not RhoA-GTP, were localized in the nucleus upon EGF stimulation. Knockdown of RhoA with siRNA resulted in the reduced levels of phosphoglycerate kinase1 (PGK1) and microtubule affinity-regulating kinase 4 (MARK). Furthermore, we found that the promoter of PGK1 was associated with ß-catenin and YAP. Notably, p-Y42 RhoA and PKM2 co-immunoprecipitated with ß-catenin and YAP. Based on these findings, we proposed a novel mechanism by which p-Y42 RhoA and PKM2, in conjunction with ß-catenin and YAP, regulate PGK1 expression, contributing to the progression of glioma upon EGF.