A Single Center Experience of Pulmonary Arterial Hypertension Management in Korea: A 25-Year Comparative Analysis Following the Introduction of Targeted Therapy.

BACKGROUND AND OBJECTIVES: The transformation of pulmonary arterial hypertension (PAH) treatment in Korea, ushered by targeted therapy's advent, prompted our analysis of baseline attributes, treatment trends, and survival shifts within our single-center registry. METHODS: We examined 230 patients (72.6% female, mean age 40.6±17.4 years) diagnosed and/or treated between 1980 and 2021 in our PAH clinic. Given targeted therapy's introduction and active use since 2007, we compared diagnostic classification, demographics, and treatment patterns at that juncture. Survival analysis encompassed PAH types and the overall population. For historical survival comparison, 50 non-registry patients were retrospectively added, and age-sex matching enabled pooled analysis. RESULTS: Congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) constituted the largest subset (43.0%), trailed by connective tissue disease-associated PAH (CTD-PAH, 29.6%) and idiopathic PAH (IPAH, 19.1%). Post-2007, CTD-PAH proportions surged, notably with an elevated initiation rate of targeted therapy (95.4%). Overall survival rates at 1, 5, and 10 years stood at 91.3%, 77.4%, and 65.8%, respectively, with CHD-PAH exhibiting superior survival to idiopathic or CTD-PAH. Age-sex matching analysis indicated survival disparities between those starting immediate targeted therapy vs. conservative treatment upon diagnosis, especially driven by IPAH. CONCLUSIONS: In the post-introduction of the targeted therapy era, patients with PAH promptly started treatment right away, and higher survival rates of patients who started initial PAH-targeted therapy were demonstrated. The transition towards early treatment initiation might have likely contributed to the elevated survival rates observed in Korea's PAH patient cohort.

All-in-one wearable drug efficacy assessment systems for bulbar muscle function using amyotrophic lateral sclerosis animal models.

Preclinical studies are crucial for developing amyotrophic lateral sclerosis drugs. Current FDA-approved drugs have been created by monitoring limb muscle function and histological analysis of amyotrophic lateral sclerosis model animals. Drug candidates for this disease have yet to be tested for bulbar-onset type due to the limitations of traditional preclinical tools: excessive animal use and discrete detection of disease progress. Here, our study introduces an all-in-one, wireless, integrated wearable system for facilitating continuous drug efficacy assessment of dysphagia-related muscles in animals during natural eating behaviors. By incorporating a kirigami-based strain-isolation mechanism, this device mounted on the skin of animals mitigates electromyography signal contamination caused by unpredictable animal movements. Our findings indicate this system, measuring the progression of motor neuron denervation, offers high precision in monitoring drug effects on dysphagia-responsible bulbar muscles. This study paves the way for more humane and efficient approaches to developing treatment solutions for degenerative neuromuscular diseases.

All-in-One, Wireless, Multi-Sensor Integrated Athlete Health Monitor for Real-Time Continuous Detection of Dehydration and Physiological Stress.

Athletes are at high risk of dehydration, fatigue, and cardiac disorders due to extreme performance in often harsh environments. Despite advancements in sports training protocols, there is an urgent need for a non-invasive system capable of comprehensive health monitoring. Although a few existing wearables measure athlete's performance, they are limited by a single function, rigidity, bulkiness, and required straps and adhesives. Here, an all-in-one, multi-sensor integrated wearable system utilizing a set of nanomembrane soft sensors and electronics, enabling wireless, real-time, continuous monitoring of saliva osmolality, skin temperature, and heart functions is introduced. This system, using a soft patch and a sensor-integrated mouthguard, provides comprehensive monitoring of an athlete's hydration and physiological stress levels. A validation study in detecting real-time physiological levels shows the device's performance in capturing moments (400-500 s) of synchronized acute elevation in dehydration (350%) and physiological strain (175%) during field training sessions. Demonstration with a few human subjects highlights the system's capability to detect early signs of health abnormality, thus improving the healthcare of sports athletes.

Programmed Follow-up and Quality Control of Treatment Techniques Enhance Chronic Thromboembolic Pulmonary Hypertension Management: Lessons From a Multidisciplinary Team.

BACKGROUND AND OBJECTIVES: The recent developments in chronic thromboembolic pulmonary hypertension (CTEPH) are emphasizing the multidisciplinary team. We report on the changes in clinical practice following the development of a multidisciplinary team, based on our 7 years of experience. METHODS: Multidisciplinary team was established in 2015 offering both balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) with technical upgrades by internal and external expertise. For operable cases, PEA was recommended as the primary treatment modality, followed by pulmonary angiography and right heart catheterization after 6 months to evaluate treatment effect and identify patients requiring further BPA. For patients with inoperable anatomy or high surgical risk, BPA was recommended as the initial treatment modality. Patient data and clinical outcomes were closely monitored. RESULTS: The number of CTEPH treatments rapidly increased and postoperative survival improved after team development. Before the team, 38 patients were treated by PEA for 18 years; however, 125 patients were treated by PEA or BPA after the team for 7 years. The number of PEA performed was 64 and that of BPA 342 sessions. World Health Organization functional class I or II was achieved in 93% of patients. The patients treated with PEA was younger, male dominant, higher pulmonary artery pressure, and smaller cardiac index, than BPA-only patients. In-hospital death after PEA was only 1 case and none after BPA. CONCLUSIONS: The balanced development of BPA and PEA through a multidisciplinary team approach proved synergistic in increasing the number of actively treated CTEPH patients and improving clinical outcomes.

Coatable strain sensors for nonplanar surfaces.

Rapidly fabricating flexible and stretchable sensors on nonplanar surfaces is crucial for wearable device applications. We employed a novel fabrication method, incorporating molds and gels into electroless plating, to enable direct printing of sensors on a wide array of surfaces, from those with up to 100 µm profile heights to hydrogels with a Young's modulus of 100 kPa. This coatable strain (CS) sensor offers several potential advantages. Firstly, it is designed to circumvent the typical limitations of limited flexibility, plastic deformation, and low repeatability found in viscoelastic polymers by being directly coated onto the surface without requiring a substrate. Secondly, it potentially increases the effective contact area and signal-to-noise ratio by eliminating voids between the sensor and the surface. Finally, the CS sensor can obtain any desired patterning at room temperature in a matter of minutes, significantly reducing energy and time consumption. In this study, we demonstrated the versatility of the CS sensor by applying it to a range of substrates, showcasing its adaptability to diverse materials, surface roughness levels, and Young's modulus values. Our primary focus was on plant growth monitoring, a challenging application that showcased the sensor's efficacy on surfaces like needles, hairy leaves, and fruits. These applications, traditionally difficult for conventional polymer-based sensors, serve to illustrate the CS sensor's potential in a range of complex environmental contexts. The successful deployment of the CS sensor in these settings suggests its broader applicability in various scientific and technological fields, potentially contributing to significant developments in the area of wearable devices and beyond.

Endovascular Treatment for Peripheral Pulmonary Arterial Stenosis in RNF213-Related Vasculopathy.

This brief report reviews the clinical, procedural, and imaging data of seven patients with p.Arg4810Lys variant of the ring finger protein 213 gene (RNF213)-related peripheral pulmonary arterial stenosis (PPAS) who underwent percutaneous transluminal pulmonary angioplasties (PTPAs) for demographics, clinical presentation, indications for BPA, and procedural and clinical outcomes. During median follow-up of 64.4 months since the first confirmed diagnosis, PTPA was performed for 62 segmental pulmonary arteries with 38 sessions of the procedure in seven patients. Vascular stent placement due to resistance to balloon dilatation and immediate elastic recoil was performed in 48/62 procedures (77%). Except for one death, six patients showed an improvement of dyspnea, five patients a decrease of mean pulmonary arterial pressure (mean 55.5 to 42.7mmHg) and increase of 6-minute walk distance (mean 415.5 to 484.3m). Reperfusion edema occurred in 4 out of 7 patients (57%), which is 6 out of 38 sessions (16%).

Flexible Thermoelectric Wearable Architecture for Wireless Continuous Physiological Monitoring.

Continuous monitoring of physiological signals from the human body is critical in health monitoring, disease diagnosis, and therapeutics. Despite the needs, the existing wearable medical devices rely on either bulky wired systems or battery-powered devices needing frequent recharging. Here, we introduce a wearable, self-powered, thermoelectric flexible system architecture for wireless portable monitoring of physiological signals without recharging batteries. This system harvests an exceptionally high open circuit voltage of 175-180 mV from the human body, powering the wireless wearable bioelectronics to detect electrophysiological signals on the skin continuously. The thermoelectric system shows long-term stability in performance for 7 days with stable power management. Integrating screen printing, laser micromachining, and soft packaging technologies enables a multilayered, soft, wearable device to be mounted on any body part. The demonstration of the self-sustainable wearable system for detecting electromyograms and electrocardiograms captures the potential of the platform technology to offer various opportunities for continuous monitoring of biosignals, remote health monitoring, and automated disease diagnosis.

Comparative Analysis of Clinical Characteristics and Prognosis Between Primary Lung Cancers Identified as Screening Detected and Incidentally Detected Pulmonary Nodules.

BACKGROUND/AIM: Although the importance of low-dose computed tomography (LDCT) screening is increasingly emphasized and implemented, many lung cancers continue to be incidentally detected during routine medical practices, and data on incidentally detected lung cancer (IDLC) remain scarce. This study aimed to investigate the clinical characteristics and prognosis of IDLCs by comparing them with screening-detected lung cancers (SDLCs). PATIENTS AND METHODS: In this retrospective study, subjects with cT1 (≤3 cm) pulmonary nodules detected on baseline computed tomography (CT), later pathologically confirmed as primary lung cancer in 2015, were included. Patients were categorized into IDLC and SDLC groups based on the setting of the first pulmonary nodule detection. RESULTS: Out of 457 subjects, 129 (28.2%) were IDLCs and 328 (71.8%) were SDLCs. The IDLC group, consisted of older individuals with a higher prevalence of smokers and underlying pulmonary disease, compared to the SDLC group. Adenocarcinomas were more frequently detected in SDLCs (87.5%) than in IDLCs (76.7%, p<0.001). The time to treatment initiation (TTI) and 5-year overall survival (OS) rates were similar. Multivariate analyses revealed underlying interstitial lung disease, DLCO, solidity of nodules and TNM stage as independent risk factors associated with mortality. Less than 30% of study participants would have been eligible for the current lung cancer screening program. CONCLUSION: The IDLC group was associated with older age, higher rate of smokers, underlying pulmonary disease, and non-adenocarcinoma histology. However, prognosis was similar to that of the SDLC group, attributable to the similarity in TNM stage, strict adherence to guidelines, and short TTI. Furthermore, less than 30% of the participants would have been suitable for the existing lung cancer screening program, indicating a potential need to reconsider the scope for screening candidates.

Tracheobronchopathia osteochondroplastica concurrent with peripheral lung cancer: a case report and perioperative considerations.

Background: Tracheobronchopathia osteochondroplastica (TPO) is a rare, benign, chronic disorder of unknown etiology. It is characterized by submucosal nodules, often calcified, which predominantly affect the anterolateral aspects of the trachea and main bronchi, while sparing the posterior bronchial wall. The co-occurrence of TPO and lung cancer is exceedingly rare. This report presents a case of TPO association with early-stage lung cancer, which was managed through surgical intervention. No active treatment was undertaken for the TPO. Case Description: A patient presented with a nodule in the right upper lobe, which was identified during a computed tomography (CT) scan of the chest, suggestive of early-stage lung cancer. Concurrently, multiple calcifications in the cartilaginous rings of the trachea were noted. Bronchoscopy revealed distinctive "pebblestone" nodules along the anterior and lateral tracheal walls, indicative of extensive TPO. The patient underwent bronchofiberscopy, which showed patency in the bronchial lumen of the right lung's upper lobe. A biopsy was not undertaken during this procedure. Comprehensive preoperative tests, including a blood biochemical examination, tumor-marker tests, lung-function tests, head-enhanced magnetic resonance imaging, abdominal ultrasound, and whole-body bone emission CT revealed no significant abnormalities. Despite this, the patient declined a whole-body positron emission tomography (PET)-CT scan. Given the potential malignancy of nodules in the right lung's upper lobe, the lobectomy for lung cancer was carried out, a procedure that would have proceeded irrespective of the presence or absence of TPO. Preoperative planning for potential tracheal intubation difficulties involved consultation with the anesthesiologist, resulting in a smooth intraoperative process. The pathology confirmed invasive adenocarcinoma. Post-surgery, the patient developed an infection in the right lung's lower lobe, identified as pseudomonas aeruginosa and Klebsiella pneumoniae through sputum culture and bronchoscopic lavage. Treatment with meropenem for 2 weeks, as guided by drug sensitivity results and respiratory advice, led to an improvement, allowing for discharge. A follow-up lung CT four months post-operation showed inflammation absorption in the right lower lobe. Conclusions: Surgical resection in cases of TPO association with lung cancer may have an increased risk of postoperative pulmonary infection. Proactive intraoperative sputum aspiration by anesthesiologists and the postoperative reinforcement of anti-infection measures, guided by drug sensitivity results, are recommended.

Surgeon Preference Regarding Wound Dressing Management in Lumbar Fusion Surgery: An AO Spine Global Cross-Sectional Study.

OBJECTIVE: To evaluate the global practice pattern of wound dressing use after lumbar fusion for degenerative conditions. METHODS: A survey issued by AO Spine Knowledge Forums Deformity and Degenerative was sent out to AO Spine members. The type of postoperative dressing employed, timing of initial dressing removal, and type of subsequent dressing applied were investigated. Differences in the type of surgery and regional distribution of surgeons' preferences were analyzed. RESULTS: Right following surgery, 60.6% utilized a dry dressing, 23.2% a plastic occlusive dressing, 5.7% glue, 6% a combination of glue and polyester mesh, 2.6% a wound vacuum, and 1.2% other dressings. The initial dressing was removed on postoperative day 1 (11.6%), 2 (39.2%), 3 (20.3%), 4 (1.7%), 5 (4.3%), 6 (0.4%), 7 or later (12.5%), or depending on drain removal (9.9%). Following initial dressing removal, 75.9% applied a dry dressing, 17.7% a plastic occlusive dressing, and 1.3% glue, while 12.1% used no dressing. The use of no additional coverage after initial dressing removal was significantly associated with a later dressing change (p < 0.001). Significant differences emerged after comparing dressing management among different AO Spine regions (p < 0.001). CONCLUSION: Most spine surgeons utilized a dry or plastic occlusive dressing initially applied after surgery. The first dressing was more frequently changed during the first 3 postoperative days and replaced with the same type of dressing. While dressing policies tended not to vary according to the type of surgery, regional differences suggest that actual practice may be based on personal experience rather than available evidence.

Endobronchial valves for emphysema and persistent air-leak: 10-year experience in an Asian country.

BACKGROUND: Endobronchial valve (EBV) therapy, a validated method for bronchoscopic lung volume reduction (BLVR) in severe emphysema, has been explored for persistent air-leak (PAL) management. However, its effectiveness and safety in the Asian population require further real-world evaluation. In this study, we assessed the outcomes of treatment with EBV within this demographic. METHODS: We conducted a retrospective analysis of medical records from 11 Korean centers. For the emphysema cohort, inclusion criteria were patients diagnosed with emphysema who underwent bronchoscopy intended for BLVR. We assessed these patients for clinical outcomes of chronic obstructive pulmonary disease. All patients with PAL who underwent treatment with EBV were included. We identified the underlying causes of PAL and evaluated clinical outcomes after the procedure. RESULTS: The severe emphysema cohort comprised 192 patients with an average age of 70.3 years, and 95.8% of them were men. Ultimately, 137 underwent treatment with EBV. Three months after the procedure, the BLVR group demonstrated a significant improvement in forced expiratory volume in 1 s (+160 mL vs. +30 mL; P = 0.009). Radiographic evidence of lung volume reduction 6 months after BLVR was significantly associated with improved survival (adjusted hazard ratio 0.020; 95% confidence interval 0.038-0.650; P = 0.010). Although pneumothorax was more common in the BLVR group (18.9% vs. 3.8%; P = 0.018), death was higher in the no-BLVR group (38.5% vs. 54.5%, P = 0.001), whereas other adverse events were comparable between the groups. Within the subset of 18 patients with PAL, the predominant causes of air-leak included spontaneous secondary pneumothorax (44.0%), parapneumonic effusion/empyema (22.2%), and post-lung resection surgery (16.7%). Following the treatment, the majority (77.8%) successfully had their chest tubes removed. Post-procedural complications were minimal, with two incidences of hemoptysis and one of empyema, all of which were effectively managed. CONCLUSIONS: Treatment with EBV provides substantial clinical benefits in the management of emphysema and PAL in the Asian population, suggesting a favorable outcome for this therapeutic approach.

Triphenylphosphonium-functionalized dimeric BODIPY-based nanoparticles for mitochondria-targeting photodynamic therapy.

The dimerization of boron dipyrromethene (BODIPY) moieties is an appealing molecular design approach for developing heavy-atom-free triplet photosensitizers (PSs). However, BODIPY dimer-based PSs generally lack target specificity, which limits their clinical use for photodynamic therapy. This study reports the synthesis of two mitochondria-targeting triphenylphosphonium (TPP)-functionalized meso-ß directly linked BODIPY dimers (BTPP and BeTPP). Both BODIPY dimers exhibited solvent-polarity-dependent singlet oxygen (1O2) quantum yields, with maximum values of 0.84 and 0.55 for BTPP and BeTPP, respectively, in tetrahydrofuran. The compact orthogonal geometry of the BODIPY dimers facilitated the generation of triplet excited states via photoinduced charge separation (CS) and subsequent spin-orbit charge-transfer intersystem crossing (SOCT-ISC) processes and their rates were dependent on the energetic configuration between the frontier molecular orbitals of the two BODIPY subunits. The as-synthesized compounds were amphiphilic and hence formed stable nanoparticles (∼36 nm in diameter) in aqueous solutions, with a zeta potential of ∼33 mV beneficial for mitochondrial targeting. In vitro experiments with MCF-7 and HeLa cancer cells indicated the effective localization of BTPP and BeTPP within cancer-cell mitochondria. Under light irradiation, BTPP and BeTPP exhibited robust photo-induced therapeutic effects in both cell lines, with half-maximal inhibitory concentration (IC50) values of ∼30 and ∼55 nM, respectively.

Ensuring spatial scalability with temporal-wise spatial attentive pooling for temporal action detection.

Recent temporal action detection models have focused on end-to-end trainable approaches to utilize the representational power of backbone networks. Despite the advantages of end-to-end trainable methods, these models still employ a small spatial resolution (e.g., 96 × 96) due to the inefficient trade-off between computational cost and spatial resolution. In this study, we argue that a simple pooling method (e.g., adaptive average pooling) acts as a bottleneck at the spatial aggregation part, restricting representational power. To address this issue, we propose a temporal-wise spatial attentive pooling (TSAP), which alleviates the bottleneck between the backbone and the detection head using a temporal-wise attention mechanism. Our approach mitigates the inefficient trade-off between spatial resolution and computational cost, thereby enhancing spatial scalability in temporal action detection. Moreover, TSAP is adaptable to previous end-to-end approaches by simply replacing the spatial pooling part. Our experiments demonstrated the essential role of spatial aggregation, and consistent improvements are observed by incorporating TSAP into previous end-to-end methods.

Comparative Study on the Efficacy of Pregabalin Versus Limaprost in Patients With Lumbar Spinal Stenosis: A Prospective, Randomized Controlled Trial.

BACKGROUND: Patients with Lumbar Spinal Stenosis (LSS) typically complain of back pain and leg pain. These symptoms reduce the quality of life (QoL) and also cause sleep disturbances. This study compares pregabalin and limaprost's efficacy in LSS for pain, disability, QoL, and sleep, aiming to offer insights for medication selection. METHODS: This study was designed as a prospective, randomized, single-center, single-blinded, clinical superiority trial targeting patients with LSS. For 6 weeks, 111 patients per group were administered medication following a standard regimen, after which patient-reported outcomes were measured. The primary outcome was the Visual Analogue Scale (VAS) for back and leg pain, and the secondary outcomes included the Oswestry Disability Index (ODI), European Quality of Life 5 Dimensions (EQ-5D), and sleep quality. RESULTS: After 6 weeks of medication, there were significant improvements over time in the primary outcome, VAS for back pain and leg pain, in both groups, but no significant difference between the 2 groups. Similarly, for the secondary outcomes, ODI and EQ-5D, both groups showed significant improvements, yet there was no significant difference between them. In the subgroup analysis targeting poor sleepers (Pittsburgh sleep quality index, PSQI >5), both groups also exhibited significant improvements in sleep quality, but again, there was no significant difference between the groups. CONCLUSIONS: Efficacy of pregabalin, limaprost in back and leg pain, ODI, EQ-5D, and sleep quality, but there was no significant difference between the 2 groups. Thus, it is advisable to prescribe based on individual drug responses and potential complications.

Transpedicular injection of rhBMP-2 with ß-tricalcium phosphate to reduce the proximal junctional kyphosis after adult spinal deformity correction: preliminary study.

The aim of this preliminary study was to assess the impact of injecting recombinant human bone morphogenetic protein-2 (rhBMP-2) with ß-tricalcium phosphate (ß-TCP) carrier into the uppermost instrumented vertebra (UIV) during surgery to prevent the development of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). The 25 patients from study group had received 0.5 mg rhBMP-2 mixed with 1.5 g ß-TCP paste injection into the UIV during surgery. The control group consisted of 75 patients who underwent surgery immediately before the start of the study. The incidences of PJK and PJF were analyzed as primary outcomes. Spinopelvic parameters and patient-reported outcomes were analyzed as secondary outcomes. Hounsfield unit (HU) measurements were performed to confirm the effect of rhBMP-2 with ß-TCP on bone formation at preoperative and postoperative at computed tomography. PJK and PJF was more occurred in control group than study group (p = 0.02, 0.29, respectively). The HU of the UIV significantly increased 6 months after surgery. And the increment at the UIV was also significantly greater than that at the UIV-1 6 months after surgery. Injection of rhBMP-2 with ß-TCP into the UIV reduced PJK and PJF rates 6 months after surgery with new bone formation.

Red fluorescent BODIPY-based nanoparticles for targeted cancer imaging-guided photodynamic therapy.

Imaging-guided diagnosis and treatment of cancer hold potential to significantly improve therapeutic accuracies and efficacies. Central to this theragnostic approach has been the use of multicomponent-based multimodal nanoparticles (NPs). Apart from this conventional approach, here we propose a design strategy for the simple and straightforward formulation of NPs based on boron dipyrromethene (BODIPY) derivatives, LaB-X (X = H, Et, and Br). Specifically, the conjugation of lactose to the inherently hydrophobic BODIPY promoted the formation of LaB-X NPs in water. Furthermore, the BODIPY backbone was subjected to distyrylation, dibromination, and diethylation to tailor the optical window and the balance between fluorescence and singlet oxygen generation capabilities. We demonstrate that while the photoinduced anticancer activities of LaB-H and LaB-Et NPs were trivial, LaB-Br NPs effectively induced the apoptotic death of hepatocellular carcinoma cells under red light irradiation while allowing fluorescence cell imaging in the phototherapeutic window. This dual fluorescence photosensitizing activity of LaB-Br NPs could be switched off and on, so that both fluorescence and singlet oxygen generation were paused during NP formation in an aqueous solution, while both processes resumed after cellular uptake, likely due to NP disassembly.

Substitution Effect of a Single Nitrogen Atom on π-Electronic Systems of Linear Polycyclic Aromatic Hydrocarbons (PAHs): Theoretically Visualized Coexistence of Mono- and Polycyclic π-Electron Delocalization.

We theoretically investigated the nitrogen substitution effect on the molecular structure and π-electron delocalization in linear nitrogen-substituted polycyclic aromatic hydrocarbons (N-PAHs). Based on the optimized molecular structures and magnetic field-induced parameters of fused bi- and tricyclic linear N-PAHs, we found that the local π-electron delocalization of subcycles (e.g., mono- and bicyclic constituent moieties) in linear N-PAHs is preserved, despite deviation from ideal structures of parent monocycles. The introduction of a fused five-membered ring with a pyrrolic N atom (N-5MR) in linear N-PAHs significantly perturbs the π-electronic condition of the neighboring fused six-membered ring (6MR). Monocyclic pyrrole exhibits substantial bond length alternations, strongly influencing the π-electronic systems of both the fused N-5MR and 6MR in linear N-PAHs, depending on the location of shared covalent bonds. A fused six-membered ring with a graphitic N atom in an indolizine moiety cannot generate monocyclic π-electron delocalization but instead contributes to the formation of polycyclic π-electron delocalization. This is evidenced by bifurcated diatropic ring currents induced by an external magnetic field. In conclusion, the satisfaction of Hückel's 4n + 2 rule for both mono- and polycycles is crucial for understanding the overall π-electron delocalization. It is crucial to consider the unique characteristics of the three types of substituted N atoms and the spatial arrangement of 5MR and 6MR in N-PAHs.

Machine learning model for circulating tumor DNA detection in chronic obstructive pulmonary disease patients with lung cancer.

Background: Patients with chronic obstructive pulmonary disease (COPD) have a high risk of developing lung cancer. Due to the high rates of complications from invasive diagnostic procedures in this population, detecting circulating tumor DNA (ctDNA) as a non-invasive method might be useful. However, clinical characteristics that are predictive of ctDNA mutation detection remain incompletely understood. This study aimed to investigate factors associated with ctDNA detection in COPD patients with lung cancer. Methods: Herein, 177 patients with COPD and lung cancer were prospectively recruited. Plasma ctDNA was genotyped using targeted deep sequencing. Comprehensive clinical variables were collected, including the emphysema index (EI), using chest computed tomography. Machine learning models were constructed to predict ctDNA detection. Results: At least one ctDNA mutation was detected in 54 (30.5%) patients. After adjustment for potential confounders, tumor stage, C-reactive protein (CRP) level, and milder emphysema were independently associated with ctDNA detection. An increase of 1% in the EI was associated with a 7% decrease in the odds of ctDNA detection (adjusted odds ratio =0.933; 95% confidence interval: 0.857-0.999; P=0.047). Machine learning models composed of multiple clinical factors predicted individuals with ctDNA mutations at high performance (AUC =0.774). Conclusions: ctDNA mutations were likely to be observed in COPD patients with lung cancer who had an advanced clinical stage, high CRP level, or milder emphysema. This was validated in machine learning models with high accuracy. Further prospective studies are required to validate the clinical utility of our findings.

Comparison of Fusion Rates among Various Demineralized Bone Matrices in Posterior Lumbar Interbody Fusion.

Background and Objectives: Posterior lumbar interbody fusion (PLIF) plays a crucial role in addressing various spinal disorders. The success of PLIF is contingent upon achieving bone fusion, as failure can lead to adverse clinical outcomes. Demineralized bone matrix (DBM) has emerged as a promising solution for promoting fusion due to its unique combination of osteoinductive and osteoconductive properties. This study aims to compare the effectiveness of three distinct DBMs (Exfuse®, Bongener®, and Bonfuse®) in achieving fusion rates in PLIF surgery. Materials and Methods: A retrospective review was conducted on 236 consecutive patients undergoing PLIF between September 2016 and February 2019. Patients over 50 years old with degenerative lumbar disease, receiving DBM, and following up for more than 12 months after surgery were included. Fusion was evaluated using the Bridwell grading system. Bridwell grades 1 and 2 were defined as 'fusion', while grades 3 and 4 were considered 'non-fusion.' Clinical outcomes were assessed using visual analog scale (VAS) scores for pain, the Oswestry disability index (ODI), and the European quality of life-5 (EQ-5D). Results: Fusion rates were 88.3% for Exfuse, 94.3% for Bongener, and 87.7% for Bonfuse, with no significant differences. All groups exhibited significant improvement in clinical outcomes at 12 months after surgery, but no significant differences were observed among the three groups. Conclusions: There were no significant differences in fusion rates and clinical outcomes among Exfuse, Bongener, and Bonfuse in PLIF surgery.

Role of invasive mediastinal nodal staging in survival outcomes of patients with non-small cell lung cancer and without radiologic lymph node metastasis: a retrospective cohort study.

Background: Lung cancer diagnostic guidelines advocate for invasive mediastinal nodal staging (IMNS), but the survival benefits of this approach in patients with non-small cell lung cancer (NSCLC) without radiologic evidence of lymph node metastasis (rN0) remain uncertain. We aimed to investigate the impact of IMNS in patients with rN0 NSCLC by comparing the long-term survival between patients who underwent IMNS and those who did not (non-IMNS). Methods: In this retrospective cohort study, we included patients with NSCLC but without radiologic evidence of lymph node metastasis from the Registry for Thoracic Cancer Surgery and the clinical data warehouse at the Samsung Medical Centre, Republic of Korea between January 2, 2008 and December 31, 2016. We compared the 5-year overall survival (OS) rate as the primary outcome after propensity score matching between the IMNS and non-IMNS groups. The age, sex, performance statue, tumor size, centrality, solidity, lung function, FDG uptake in PET-CT, and histological examination of the tumor before surgery were matched. Findings: A total of 4545 patients (887 in the IMNS group and 3658 in the non-IMNS group) who received curative treatment for NSCLC were included in this study. By the mediastinal node dissection, the overall incidence of unforeseen mediastinal node metastasis (N2) was 7.2% (317/4378 patients). Despite the IMNS, 67% of pathological N2 was missed (61/91 patients with unforeseen N2). Based on propensity score matching, 866 patients each for the IMNS and non-IMNS groups were assigned. There was no significant difference in 5-year OS and recurrence-free survival (RFS) between two groups: 5-year OS was 73.9% (95% confidence interval, CI: 71%-77%) for IMNS and 71.7% (95% CI: 68.6%-74.9%; p = 0.23), for non-IMNS (hazard ratio, HR 0.90, 95% CI: 0.77-1.07), while 5-year RFS was 64.7% (95% CI: 61.5%-68.2%) and 67.5% (95% CI: 64.3%-70.9%; p = 0.35 (HR 1.08, 95% CI: 0.92-1.27), respectively. Moreover, the timing and locations of recurrence were similar in both groups. Interpretation: IMNS might not be required before surgery for patients with NSCLC without LN suspicious of metastasis. Further randomised trials are required to validate the findings of the present study. Funding: None.