Seasonal influences on the efficacy of anti-programmed cell death (ligand) 1 inhibitors in lung cancer.

BACKGROUND: Seasonal variations in systemic immunity have been reported. This study aimed to evaluate whether seasonality affects the efficacy of anticancer immunotherapy. METHODS: A total of 604 patients with lung cancer receiving single anti-programmed cell death (ligand) 1 (anti-PD-[L]1) inhibitors from two prospective observational cohorts were screened. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Patients were classified into two groups according to the season when the treatment started: winter (November-February) and other seasons (March-October). Kaplan-Meier analysis and Cox proportional hazards models were fitted to evaluate the impact of seasonality on survival. For validation, propensity score matching was performed. RESULTS: A total of 484 patients with advanced non-small cell lung cancer were included. In an unmatched population, multivariable analysis demonstrated that the winter group (n = 173) had a significantly lower risk of progression or death from immunotherapy than the other group (n = 311) (PFS: hazard ratio [HR], 0.77 [95% confidence interval (CI), 0.62-0.96]; p = .018; OS: HR, 0.77 [95% CI, 0.1-0.98]; p = .032). In a propensity score-matched population, the winter group (n = 162) showed significantly longer median PFS (2.8 months [95% CI, 1.9-4.1 months] vs. 2.0 months [95% CI, 1.4-2.7 months]; p = .009) than the other group (n = 162). The winter group's median OS was also significantly longer than that of the other group (13.4 months [95% CI, 10.2-18.0 months] vs. 8.0 months [95% CI, 3.6-8.7 months]; p = .012). The trend toward longer survival in the winter group continued in subgroup analyses. CONCLUSIONS: Starting an anti-PD-(L)1 inhibitor in winter was associated with better treatment outcomes in patients with lung cancer compared to other seasons.

PWWP2B promotes DNA end resection and homologous recombination.

Genome instability is one of the leading causes of gastric cancers. However, the mutational landscape of driver genes in gastric cancer is poorly understood. Here, we investigate somatic mutations in 25 Korean gastric adenocarcinoma patients using whole-exome sequencing and show that PWWP2B is one of the most frequently mutated genes. PWWP2B mutation correlates with lower cancer patient survival. We find that PWWP2B has a role in DNA double-strand break repair. As a nuclear protein, PWWP2B moves to sites of DNA damage through its interaction with UHRF1. Depletion of PWWP2B enhances cellular sensitivity to ionizing radiation (IR) and impairs IR-induced foci formation of RAD51. PWWP2B interacts with MRE11 and participates in homologous recombination via promoting DNA end-resection. Taken together, our data show that PWWP2B facilitates the recruitment of DNA repair machinery to sites of DNA damage and promotes HR-mediated DNA double-strand break repair. Impaired PWWP2B function might thus cause genome instability and promote gastric cancer development.

Augmentation of keratinized tissue using autogenous soft-tissue grafts and collagen-based soft-tissue substitutes at teeth and dental implants: Histological findings in a pilot pre-clinical study.

AIM: To histomorphometrically assess three treatment modalities for gaining keratinized tissue (KT) at teeth and at dental implants. MATERIALS AND METHODS: In five dogs, the distal roots of the mandibular second, third and fourth premolars were extracted. Dental implants were placed at the distal root areas 2 months later. After another 2 months, KT augmentation was performed at both distal (implants) and at mesial root (teeth) areas in the presence (wKT groups) or absence (w/oKT groups) of a KT band at the mucosal/gingival level. Three treatment modalities were applied randomly: apically positioned flap only (APF), free gingival grafts (FGGs) and xenogeneic collagen matrices (XCMs). A combination of the above produced six groups. Two months later, tissue sections were harvested and analysed histomorphometrically. RESULTS: The median KT height and length were greatest at implants with FGG in both wKT (3.7 and 5.1 mm, respectively) and w/oKT groups (3.7 and 4.6 mm), and at teeth with FGG in wKT groups (3.7 and 6.1 mm) and with APF in the w/oKT groups (3.9 and 4.4 mm). The XCM and APF produced more favourable results at teeth than at implants. CONCLUSIONS: FGG was advantageous in gaining KT, especially at implants.

Effects of implant placement timing and type of soft-tissue grafting on histological and histomorphometric outcomes in a preclinical canine model.

AIM: To determine the effects of implant timing and type of soft-tissue grafting on histological and histomorphometric outcomes in a preclinical model. MATERIALS AND METHODS: Four implant placement protocols were randomly applied at the mesial root sites of the third and fourth mandibular premolars in 10 mongrel dogs: immediate placement (group IP), early placement (group EP), delayed placement with/without alveolar ridge preservation (groups ARP and DP, respectively). A connective-tissue graft (CTG) or porcine-derived volume-stable collagen matrix (VCMX) was applied to enhance the ridge profile (simultaneously with implant placement in group IP and staged for others), resulting in five sites for each combination. All dogs were sacrificed 3 months after soft-tissue grafting. Histological and histomorphometric analyses were performed, and the data were analysed descriptively. RESULTS: CTG and VCMX were difficult to differentiate from the augmented area. The median total tissue thickness on the buccal aspect of the implant was largest in group IP/CTG (between 2.78 and 3.87 mm). The soft-tissue thickness was generally favourable with CTG at all implant placement timings. Within the DP groups, CTG yielded statistically significantly larger total and soft-tissue thickness than VCMX (p < .05). Among the groups with VCMX, group EP/VCMX showed the largest soft-tissue thickness at apical levels to the implant shoulder. CONCLUSIONS: CTG generally led to greater tissue thickness than VCMX.

Diesel exhaust particle exposure exacerbates ciliary and epithelial barrier dysfunction in the multiciliated bronchial epithelium models.

Airway epithelium, the first defense barrier of the respiratory system, facilitates mucociliary clearance against inflammatory stimuli, such as pathogens and particulates inhaled into the airway and lung. Inhaled particulate matter 2.5 (PM2.5) can penetrate the alveolar region of the lung, and it can develop and exacerbate respiratory diseases. Although the pathophysiological effects of PM2.5 in the respiratory system are well known, its impact on mucociliary clearance of airway epithelium has yet to be clearly defined. In this study, we used two different 3D in vitro airway models, namely the EpiAirway-full-thickness (FT) model and a normal human bronchial epithelial cell (NHBE)-based air-liquid interface (ALI) system, to investigate the effect of diesel exhaust particles (DEPs) belonging to PM2.5 on mucociliary clearance. RNA-sequencing (RNA-Seq) analyses of EpiAirway-FT exposed to DEPs indicated that DEP-induced differentially expressed genes (DEGs) are related to ciliary and microtubule function and inflammatory-related pathways. The exposure to DEPs significantly decreased the number of ciliated cells and shortened ciliary length. It reduced the expression of cilium-related genes such as acetylated α-tubulin, ARL13B, DNAH5, and DNAL1 in the NHBEs cultured in the ALI system. Furthermore, DEPs significantly increased the expression of MUC5AC, whereas they decreased the expression of epithelial junction proteins, namely, ZO1, Occludin, and E-cadherin. Impairment of mucociliary clearance by DEPs significantly improved the release of epithelial-derived inflammatory and fibrotic mediators such as IL-1ß, IL-6, IL-8, GM-CSF, MMP-1, VEGF, and S100A9. Taken together, it can be speculated that DEPs can cause ciliary dysfunction, hyperplasia of goblet cells, and the disruption of the epithelial barrier, resulting in the hyperproduction of lung injury mediators. Our data strongly suggest that PM2.5 exposure is directly associated with ciliary and epithelial barrier dysfunction and may exacerbate lung injury.

Evaluating Linkage Quality of Population-Based Administrative Data for Health Service Research.

BACKGROUND: To overcome the limitations of relying on data from a single institution, many researchers have studied data linkage methodologies. Data linkage includes errors owing to legal issues surrounding personal information and technical issues related to data processing. Linkage errors affect selection bias, and external and internal validity. Therefore, quality verification for each connection method with adherence to personal information protection is an important issue. This study evaluated the linkage quality of linked data and analyzed the potential bias resulting from linkage errors. METHODS: This study analyzed claims data submitted to the Health Insurance Review and Assessment Service (HIRA DATA). The linkage errors of the two deterministic linkage methods were evaluated based on the use of the match key. The first deterministic linkage uses a unique identification number, and the second deterministic linkage uses the name, gender, and date of birth as a set of partial identifiers. The linkage error included in this deterministic linkage method was compared with the absolute standardized difference (ASD) of Cohen's according to the baseline characteristics, and the linkage quality was evaluated through the following indicators: linked rate, false match rate, missed match rate, positive predictive value, sensitivity, specificity, and F1-score. RESULTS: For the deterministic linkage method that used the name, gender, and date of birth as a set of partial identifiers, the true match rate was 83.5 and the missed match rate was 16.5. Although there was bias in some characteristics of the data, most of the ASD values were less than 0.1, with no case greater than 0.5. Therefore, it is difficult to determine whether linked data constructed with deterministic linkages have substantial differences. CONCLUSION: This study confirms the possibility of building health and medical data at the national level as the first data linkage quality verification study using big data from the HIRA. Analyzing the quality of linkages is crucial for comprehending linkage errors and generating reliable analytical outcomes. Linkers should increase the reliability of linked data by providing linkage error-related information to researchers. The results of this study will serve as reference data to increase the reliability of multicenter data linkage studies.

Endoscopic ultrasound-rendezvous versus percutaneous-endoscopic rendezvous endoscopic retrograde cholangiopancreatography for bile duct access: Systematic review and meta-analysis.

OBJECTIVES: Endoscopic ultrasound (EUS) or percutaneous-assisted antegrade guidewire insertion can be used to achieve biliary access when standard endoscopic retrograde cholangiopancreatography (ERCP) fails. We conducted a systematic review and meta-analysis to evaluate and compare the effectiveness and safety of EUS-assisted rendezvous (EUS-RV) and percutaneous rendezvous (PERC-RV) ERCP. METHODS: We searched multiple databases from inception to September 2022 to identify studies reporting on EUS-RV and PERC-RV in failed ERCP. A random-effects model was used to summarize the pooled rates of technical success and adverse events with 95% confidence interval (CI). RESULTS: In total, 524 patients (19 studies) and 591 patients (12 studies) were managed by EUS-RV and PERC-RV, respectively. The pooled technical successes were 88.7% (95% CI 84.6-92.8%, I2 = 70.5%) for EUS-RV and 94.1% (95% CI 91.1-97.1%, I2 = 59.2%) for PERC-RV (P = 0.088). The technical success rates of EUS-RV and PERC-RV were comparable in subgroups of benign diseases (89.2% vs. 95.8%, P = 0.068), malignant diseases (90.3% vs. 95.5%, P = 0.193), and normal anatomy (90.7% vs. 95.9%, P = 0.240). However, patients with surgically altered anatomy had poorer technical success after EUS-RV than after PERC-RV (58.7% vs. 93.1%, P = 0.036). The pooled rates of overall adverse events were 9.8% for EUS-RV and 13.4% for PERC-RV (P = 0.686). CONCLUSIONS: Both EUS-RV and PERC-RV have exhibited high technical success rates. When standard ERCP fails, EUS-RV and PERC-RV are comparably effective rescue techniques if adequate expertise and facilities are feasible. However, in patients with surgically altered anatomy, PERC-RV might be the preferred choice over EUS-RV because of its higher technical success rate.

Development of a prediction model for cognitive impairment of sarcopenia using multimodal neuroimaging in non-demented older adults.

INTRODUCTION: Despite prior research on the association between sarcopenia and cognitive impairment in the elderly, a comprehensive model that integrates various brain pathologies is still lacking. METHODS: We used data from 528 non-demented older adults with or without sarcopenia in the Catholic Aging Brain Imaging (CABI) database, containing magnetic resonance imaging scans, positron emission tomography scans, and clinical data. We also measured three key components of sarcopenia: skeletal muscle index (SMI), hand grip strength (HGS), and the five times sit-to-stand test (5STS). RESULTS: All components of sarcopenia were significantly correlated with global cognitive function, but cortical thickness and amyloid-beta (Aß) retention had distinctive relationships with each measure. In the path model, brain atrophy resulting in cognitive impairment was mediated by Aß retention for SMI and periventricular white matter hyperintensity for HGS, but directly affected by the 5STS. DISCUSSION: Treatments targeting each sub-domain of sarcopenia should be considered to prevent cognitive decline. HIGHLIGHTS: We identified distinct impacts of three sarcopenia measures on brain structure and Aß. Muscle mass is mainly associated with Aß and has an influence on the brain atrophy. Muscle strength linked with periventricular WMH and brain atrophy. Muscle function associated with cortical thinning in specific brain regions. Interventions on sarcopenia may be important to ease cognitive decline in the elderly.

Effects of TiO2 Nanotubes and Reduced Graphene Oxide on Streptococcus mutans and Preosteoblastic Cells at an Early Stage.

The effects of TiO2 nanotube (TNT) and reduced graphene oxide (rGO) deposition onto titanium, which is widely used in dental implants, on Streptococcus mutans (S. mutans) and preosteoblastic cells were evaluated. TNTs were formed through anodic oxidation on pure titanium, and rGO was deposited using an atmospheric plasma generator. The specimens used were divided into a control group of titanium specimens and three experimental groups: Group N (specimens with TNT formation), Group G (rGO-deposited specimens), and Group NG (specimens under rGO deposition after TNT formation). Adhesion of S. mutans to the surface was assessed after 24 h of culture using a crystal violet assay, while adhesion and proliferation of MC3T3-E1 cells, a mouse preosteoblastic cell line, were evaluated after 24 and 72 h through a water-soluble tetrazolium salt assay. TNT formation and rGO deposition on titanium decreased S. mutans adhesion (p < 0.05) and increased MC3T3-E1 cell adhesion and proliferation (p < 0.0083). In Group NG, S. mutans adhesion was the lowest (p < 0.05), while MC3T3-E1 cell proliferation was the highest (p < 0.0083). In this study, TNT formation and rGO deposition on a pure titanium surface inhibited the adhesion of S. mutans at an early stage and increased the initial adhesion and proliferation of preosteoblastic cells.

Potential Molecular Markers Related to Lymph Node Metastasis and Stalk Resection Margins in Pedunculated T1 Colorectal Cancers Using Digital Spatial Profiling: A Pilot Study with a Small Case Series.

There is a debate regarding the prediction of lymph node metastasis (LNM) in pedunculated T1 colorectal cancer (CRC). In this study with four cases of pedunculated T1 CRCs, we aimed to investigate gene expression variations based on the distance from the Haggitt line (HL) and identify potential molecular risk factors for LNM. By leveraging the Cancer Transcriptome Atlas and digital spatial profiling technology, we meticulously analyzed discrete regions, including the head, HL, proximal stalk region (300-1000 µm from HL), and distal stalk region (1500-2000 µm from HL) to identify spatially sequential molecular changes. Our findings showed significant overall gene expression variations among the head, proximal stalk, and distal stalk regions of pedunculated T1 CRCs compared to the control adenoma. Compared to LNM-negative T1 CRCs, LNM-positive T1 CRC showed that the expression of genes involved in immune-related pathways such as B2M, HLA-B, and HLA-E were significantly downregulated in the distal stalk region compared to the proximal stalk region. In summary, our results may tentatively suggest considering endoscopic resection of the stalk with a minimum 2000 µm margin from the HL, taking into account the gene expression alterations related to immune-related pathways. However, we acknowledge the limitations of this pilot study, notably the small case series, which may restrict the depth of interpretation. Further validation is imperative to substantiate these findings.

A Novel Approach for the Treatment of Recurrent Oroantral Fistula Occurring at an Infected Sinus Augmentation Site.

Closing a recurrent oroantral fistula (OAF) that occurs at an infected sinus augmentation site is a challenge for clinicians. The recurrent OAF has a detrimental impact on bone regeneration and subsequent implant placement. This case report includes three cases in which sinus graft infection and OAF occurred after maxillary sinus augmentation (MSA). In these cases, treatments to control sinus infection were performed using an otolaryngologist; then, intraoral interventions comprising mucosal flap procedures, bone grafts, and barrier membrane applications were performed 2-5 times by oral surgeons. Nevertheless, OAF recurred persistently. The failure to stop OAF recurrence may be due to the inability to effectively block air pressure at the OAF site. Following a comprehensive debridement of the infected tissue at the previous sinus augmentation site, a pouch was created through sinus mucosal elevation. The perforated sinus mucosa at the OAF site was covered with a non-resorbable membrane in one case and with resorbable collagen membranes in the other two cases, followed by bone grafting within the pouch. Lastly, this procedure was completed by blocking the entrance of the pouch with a cortical bone shell graft and a resorbable collagen membrane. The cortical bone shell graft, obstructing the air pressure from the nasal cavity, facilitated bone formation, and, ultimately, allowed for implant placement. Within the limitations of the present case report, the application of a guided bone regeneration technique involving a cortical bone shell graft and a barrier membrane enabled the closure of the recurrent OAF and subsequent implant placement.

Revealing oxidative pentose metabolism in new Pseudomonas putida isolates.

The Pseudomonas putida group in the Gammaproteobacteria has been intensively studied for bioremediation and plant growth promotion. Members of this group have recently emerged as promising hosts to convert intermediates derived from plant biomass to biofuels and biochemicals. However, most strains of P. putida cannot metabolize pentose sugars derived from hemicellulose. Here, we describe three isolates that provide a broader view of the pentose sugar catabolism in the P. putida group. One of these isolates clusters with the well-characterized P. alloputida KT2440 (Strain BP6); the second isolate clustered with plant growth-promoting strain P. putida W619 (Strain M2), while the third isolate represents a new species in the group (Strain BP8). Each of these isolates possessed homologous genes for oxidative xylose catabolism (xylDXA) and a potential xylonate transporter. Strain M2 grew on arabinose and had genes for oxidative arabinose catabolism (araDXA). A CRISPR interference (CRISPRi) system was developed for strain M2 and identified conditionally essential genes for xylose growth. A glucose dehydrogenase was found to be responsible for initial oxidation of xylose and arabinose in strain M2. These isolates have illuminated inherent diversity in pentose catabolism in the P. putida group and may provide alternative hosts for biomass conversion.

Laboratory evolution reveals general and specific tolerance mechanisms for commodity chemicals.

Although strain tolerance to high product concentrations is a barrier to the economically viable biomanufacturing of industrial chemicals, chemical tolerance mechanisms are often unknown. To reveal tolerance mechanisms, an automated platform was utilized to evolve Escherichia coli to grow optimally in the presence of 11 industrial chemicals (1,2-propanediol, 2,3-butanediol, glutarate, adipate, putrescine, hexamethylenediamine, butanol, isobutyrate, coumarate, octanoate, hexanoate), reaching tolerance at concentrations 60%-400% higher than initial toxic levels. Sequencing genomes of 223 isolates from 89 populations, reverse engineering, and cross-compound tolerance profiling were employed to uncover tolerance mechanisms. We show that: 1) cells are tolerized via frequent mutation of membrane transporters or cell wall-associated proteins (e.g., ProV, KgtP, SapB, NagA, NagC, MreB), transcription and translation machineries (e.g., RpoA, RpoB, RpoC, RpsA, RpsG, NusA, Rho), stress signaling proteins (e.g., RelA, SspA, SpoT, YobF), and for certain chemicals, regulators and enzymes in metabolism (e.g., MetJ, NadR, GudD, PurT); 2) osmotic stress plays a significant role in tolerance when chemical concentrations exceed a general threshold and mutated genes frequently overlap with those enabling chemical tolerance in membrane transporters and cell wall-associated proteins; 3) tolerization to a specific chemical generally improves tolerance to structurally similar compounds whereas a tradeoff can occur on dissimilar chemicals, and 4) using pre-tolerized starting isolates can hugely enhance the subsequent production of chemicals when a production pathway is inserted in many, but not all, evolved tolerized host strains, underpinning the need for evolving multiple parallel populations. Taken as a whole, this study provides a comprehensive genotype-phenotype map based on identified mutations and growth phenotypes for 223 chemical tolerant isolates.

Expanding SPG7 dominant optic atrophy phenotype: Infantile nystagmus and optic atrophy without spastic paraplegia.

Spastic paraplegia is a neurodegenerative disorder characterized by progressive leg weakness and spasticity due to degeneration of corticospinal axons. SPG7 encodes paraplegin, and pathogenic variants in the gene cause hereditary spastic paraplegia as an autosomal recessive trait. Various ophthalmological findings including optic atrophy, ophthalmoplegia, or nystagmus have been reported in patients with spastic paraplegia type 7. We report a 15-year-old male patient with a novel heterozygous variant, c.1224T>G:p.(Asp408Glu) in SPG7 (NM_003119.3) causing early onset isolated optic atrophy and infantile nystagmus prior to the onset of neurological symptoms. Therefore, SPG7 should be considered a cause of infantile nystagmus with optic atrophy.

Deep learning-based clinical decision support system for gastric neoplasms in real-time endoscopy: development and validation study.

BACKGROUND : Deep learning models have previously been established to predict the histopathology and invasion depth of gastric lesions using endoscopic images. This study aimed to establish and validate a deep learning-based clinical decision support system (CDSS) for the automated detection and classification (diagnosis and invasion depth prediction) of gastric neoplasms in real-time endoscopy. METHODS : The same 5017 endoscopic images that were employed to establish previous models were used for the training data. The primary outcomes were: (i) the lesion detection rate for the detection model, and (ii) the lesion classification accuracy for the classification model. For performance validation of the lesion detection model, 2524 real-time procedures were tested in a randomized pilot study. Consecutive patients were allocated either to CDSS-assisted or conventional screening endoscopy. The lesion detection rate was compared between the groups. For performance validation of the lesion classification model, a prospective multicenter external test was conducted using 3976 novel images from five institutions. RESULTS : The lesion detection rate was 95.6 % (internal test). On performance validation, CDSS-assisted endoscopy showed a higher lesion detection rate than conventional screening endoscopy, although statistically not significant (2.0 % vs. 1.3 %; P = 0.21) (randomized study). The lesion classification rate was 89.7 % in the four-class classification (advanced gastric cancer, early gastric cancer, dysplasia, and non-neoplastic) and 89.2 % in the invasion depth prediction (mucosa confined or submucosa invaded; internal test). On performance validation, the CDSS reached 81.5 % accuracy in the four-class classification and 86.4 % accuracy in the binary classification (prospective multicenter external test). CONCLUSIONS : The CDSS demonstrated its potential for real-life clinical application and high performance in terms of lesion detection and classification of detected lesions in the stomach.

Evidence for the circulation of genotype 4 Eurasian avian-like lineage swine H1N1 influenza A viruses on Korean swine farms, obtained using a newly developed one-step multiplex RT-qPCR assay.

Genotype 4 (G4) Eurasian avian-like lineage swine H1N1 influenza A viruses, which are reassortants containing sequences from the pandemic 2009 H1N1 virus lineage, triple-reassortant-lineage internal genes, and EA-lineage external genes, have been reported in China since 2013. These have been predominant in pig populations since 2016 and have exhibited pandemic potential. In this study, we developed a one-step multiplex RT-qPCR assay targeting the M, HA1, and PB2 genes to detect G4 and related EA H1N1 viruses, with detection limits of 1.5 × 101 copies/µL and 1.15 × 10-2 ng/µL for the purified PCR products and RNA templates, respectively. The specificity of the detection method was confirmed using various influenza virus subtypes. When the one-step multiplex RT-qPCR assay was applied to swine respiratory samples collected between 2020 and 2022 in Korea, a virus related to G4 EA H1N1 strains was detected. Phylogenetic analysis based on portions of all eight genome segments showed that the positive sample contained HA, NA, PB2, NS, and NP genes closely related to those of G4 EA H1N1 viruses, confirming the ability of our assay to accurately detect G4 EA H1N1 viruses in the field.

Efficacy comparison of 7- and 14-day P-CAB based bismuth-containing quadruple regimen with PPI based bismuth-containing quadruple regimen for Helicobacter pylori infection: rationale and design of an open-label, multicenter, randomized controlled trial.

BACKGROUND: Owing to its strong acid inhibition, potassium-competitive acid blocker (P-CAB) based regimens for Helicobacter pylori (H. pylori) eradication are expected to offer clinical advantages over proton pump inhibitor (PPI) based regimens. This study aims to compare the efficacy and adverse effects of a 7-day and a 14-day P-CAB-based bismuth-containing quadruple regimen (PC-BMT) with those of a 14-day PPI-based bismuth-containing quadruple regimen (P-BMT) in patients with high clarithromycin resistance. METHODS: This randomized multicenter controlled clinical trial will be performed at five teaching hospitals in Korea. Patients with H. pylori infection who are naive to treatment will be randomized into one of three regimens: 7-day or 14-day PC-BMT (tegoprazan 50 mg BID, bismuth subcitrate 300 mg QID, metronidazole 500 mg TID, and tetracycline 500 mg QID) or 14-day P-BMT. The eradication rate, treatment-related adverse events, and drug compliance will be evaluated and compared among the three groups. Antibiotic resistance testing by culture will be conducted during the trial, and these data will be used to interpret the results. A total of 366 patients will be randomized to receive 7-day PC-BMT (n = 122), 14-day PC-BMT (n = 122), or 14-day P-BMT (n = 122). The H. pylori eradication rates in the PC-BMT and P-BMT groups will be compared using intention-to-treat and per-protocol analyses. DISCUSSION: This study will demonstrate that the 7-day or 14-day PC-BMT is well tolerated and achieve similar eradication rates to those of 14-day P-BMT. Additionally, the 7-day PC-BMT will show fewer treatment-related adverse effects and higher drug compliance, owing to its reduced treatment duration. TRIAL REGISTRATION: Korean Clinical Research Information Service registry, KCT0007444. Registered on 28 June 2022, https://cris.nih.go.kr/cris/index/index.do .

Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.

BACKGROUND: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION: NCT04080726 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.

Peroxymonosulfate-Based Electrochemical Advanced Oxidation: Complication by Oxygen Reduction Reaction.

Peroxymonosulfate (PMS)-based electrochemical advanced oxidation processes (EAOPs) have received widespread attention in recent years, but the precise nature of PMS activation and its impact on the overall process performance remain poorly understood. This study presents the first demonstration of the critical role played by the oxygen reduction reaction in the effective utilization of PMS and the subsequent enhancement of overall pollutant remediation. We observed the concurrent generation of H2O2 via oxygen reduction during the cathodic PMS activation by a model nitrogen-doped carbon nanotube catalyst. A complex interplay between H2O2 generation and PMS activation, as well as a locally increased pH near the electrode due to the oxygen reduction reaction, resulted in a SO4•-/•OH-mixed oxidation environment that facilitated pollutant degradation. The findings of this study highlight a unique dependency between PMS-driven and H2O2-driven EAOPs and a new perspective on a previously unexplored route for further enhancing PMS-based treatment processes.

Palladium Single-Atom (In)Stability Under Aqueous Reductive Conditions.

Here, we investigate the stability and performance of single-atom Pd on TiO2 for the selective dechlorination of 4-chlorophenol. A challenge inherent to single atoms is their high surface free energy, which results in a tendency for the surface migration and aggregation of metal atoms. This work evaluates various factors affecting the stability of Pd single-atoms, including atomic dispersion, coordination environment, and substrate properties, under reductive aqueous conditions. The transition from single atoms to clusters vastly enhanced dechlorination kinetics without diminishing carbon-chlorine bond selectivity. X-ray absorption spectroscopy analysis using both in situ and ex situ conditions followed the dynamic transformation of single atoms into amorphous clusters, which consist of a unique unsaturated coordination environment and few nanometer diameter. The intricate relationship between stability and performance underscores the vital role of detailed characterization to properly determine the true active species for dehalogenation reactions.