O-GlcNAc Transferase Suppresses Inflammation and Necroptosis by Targeting Receptor-Interacting Serine/Threonine-Protein Kinase 3.

Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis. However, the role of individual glucose metabolic pathways during immune cell activation and inflammation remains incompletely understood. Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked ß-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP). Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation. Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation. Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling. Thus, our study identifies an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation and highlights the importance of glucose metabolism in septic inflammation.

Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation.

TET proteins oxidize 5-methylcytosine (5mC) on DNA and play important roles in various biological processes. Mutations of TET2 are frequently observed in myeloid malignance. Here, we present the crystal structure of human TET2 bound to methylated DNA at 2.02 Å resolution. The structure shows that two zinc fingers bring the Cys-rich and DSBH domains together to form a compact catalytic domain. The Cys-rich domain stabilizes the DNA above the DSBH core. TET2 specifically recognizes CpG dinucleotide and shows substrate preference for 5mC in a CpG context. 5mC is inserted into the catalytic cavity with the methyl group orientated to catalytic Fe(II) for reaction. The methyl group is not involved in TET2-DNA contacts so that the catalytic cavity allows TET2 to accommodate 5mC derivatives for further oxidation. Mutations of Fe(II)/NOG-chelating, DNA-interacting, and zinc-chelating residues are frequently observed in human cancers. Our studies provide a structural basis for understanding the mechanisms of TET-mediated 5mC oxidation.

Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction: A Multicenter, Randomized, Double-Blind Trial.

BACKGROUND: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice. METHODS: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours. Before trial initiation, each center selected 1 of 3 PPA regimens (40 mg of enoxaparin once daily subcutaneously; 10 U·kg·h of unfractionated heparin intravenously, adjusted to maintain activated clotting time between 150 and 220 seconds; or 0.2 mg·kg·h of bivalirudin intravenously). The primary efficacy objective was to demonstrate superiority of PPA to reduce the primary efficacy end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, stent thrombosis (definite), or urgent revascularization (any vessel) within 30 days. The key secondary objective was to evaluate the effect of each specific anticoagulation regimen (enoxaparin, unfractionated heparin, or bivalirudin) on the primary efficacy end point. The primary safety end point was Bleeding Academic Research Consortium 3 to 5 bleeding at 30 days. RESULTS: Between January 10, 2019, and September 18, 2021, a total of 2989 patients were randomized. The primary efficacy end point occurred in 37 patients (2.5%) in both the PPA and placebo groups (hazard ratio, 1.00 [95% CI, 0.63 to 1.57]). The incidence of Bleeding Academic Research Consortium 3 to 5 bleeding did not differ between the PPA and placebo groups (8 [0.5%] vs 11 [0.7%] patients; hazard ratio, 0.74 [95% CI, 0.30 to 1.83]). CONCLUSIONS: Routine PPA after primary percutaneous coronary intervention was safe but did not reduce 30-day ischemic events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03664180.

Leveraging Isoreticular Principle to Elucidate the Key Role of Inherent Hydrogen-Bonding Anchoring Sites in Enhancing Water Sorption Cyclability of Zr(IV) Metal-Organic Frameworks.

Water adsorption/desorption cyclability of porous materials is a prerequisite for diverse applications, including atmospheric water harvesting (AWH), humidity autocontrol (HAC), heat pumps and chillers, and hydrolytic catalysis. However, unambiguous molecular insights into the correlation between underlying building blocks and the cyclability are still highly elusive. In this work, by taking advantage of the well-established isoreticular synthetic principle in Zr(IV) metal-organic frameworks (Zr-MOFs), we show that the inherent density of hydrogen atoms in the organic skeleton can play a key role in regulating the water sorption cyclability of MOFs. The ease of isoreticular practice of Zr-MOFs enables the successful syntheses of two pairs of isostructural Zr-MOFs (NU-901 and NU-903, NU-950 and SJTU-9) from pyrene- or benzene-cored carboxylate linkers, which feature scu and sqc topological nets, respectively. NU-901 and NU-950 comprised of pyrene skeletons carrying more hydrogen-bonding anchoring sites show distinctly inferior cyclability as compared with NU-903 and SJTU-9 built of benzene units. Single-crystal X-ray crystallography analysis of the hydrated structure clearly unveils the water molecule-involved interactions with the hydrogen-bonding donors of benzene moieties. Remarkably, NU-903 and SJTU-9 isomers exhibit outstanding water vapor sorption capacities as well as working capacities at the desired humidity range with potential implementations covering indoor humidity control and water harvesting. Our findings uncover the importance of hydrogen-bonding anchoring site engineering of organic scaffold in manipulating the framework durability toward water sorption cycle and will also likely facilitate the rational design and development of highly robust porous materials.

Chiral Reticular Chemistry: A Tailored Approach Crafting Highly Porous and Hydrolytically Robust Metal-Organic Frameworks for Intelligent Humidity Control.

Control of humidity within confined spaces is critical for maintaining air quality and human well-being, with implications for environments ranging from international space stations and pharmacies to granaries and cultural relic preservation sites. However, existing techniques rely on energy-intensive electrically driven equipment or complex temperature and humidity control (THC) systems, resulting in imprecision and inconvenience. The development of innovative techniques and materials capable of simultaneously meeting the stringent requirements of practical applications holds the key to creating intelligent and energy-efficient humidity control devices. In this study, we introduce chiral reticular chemistry as a tailored synthetic approach, targeting a highly porous hea topological framework characterized by intrinsic interpenetrating pore architecture. This groundbreaking design successfully circumvents the traditional compromise between the pore volume and hydrolytic stability. Our metal-organic framework (MOF) exhibits an extraordinary working capacity, setting a new record at 1.35 g g-1 within the relative humidity (RH) range of 40-60%, without exhibiting hysteresis. Consequently, it emerges as a state-of-the-art candidate for intelligent humidity regulation within confined spaces. Utilizing single-crystal X-ray measurements and molecular simulations, we unequivocally elucidate the mechanism of water clustering and pore filling, underscoring the pivotal role of the linker functionality in governing the water seeding process. Our findings represent a significant advancement in the field, paving the way for the development of highly efficient humidity control technologies and offering promising solutions for diverse real-world scenarios.

An engineered Escherichia coli Nissle strain prevents lethal liver injury in a mouse model of tyrosinemia type 1.

BACKGROUND & AIMS: Hereditary tyrosinemia type 1 (HT1) results from the loss of fumarylacetoacetate hydrolase (FAH) activity and can lead to lethal liver injury. Therapeutic options for HT1 remain limited. In this study, we aimed to construct an engineered bacterium capable of reprogramming host metabolism and thereby provide a potential alternative approach for the treatment of HT1. METHODS: Escherichia coli Nissle 1917 (EcN) was engineered to express genes involved in tyrosine metabolism in the anoxic conditions that are characteristic of the intestine (EcN-HT). Bodyweight, survival rate, plasma (tyrosine/liver function), H&E staining and RNA sequencing were used to assess its ability to degrade tyrosine and protect against lethal liver injury in Fah-knockout (KO) mice, a well-accepted model of HT1. RESULTS: EcN-HT consumed tyrosine and produced L-DOPA (levodopa) in an in vitro system. Importantly, in Fah-KO mice, the oral administration of EcN-HT enhanced tyrosine degradation, reduced the accumulation of toxic metabolites, and protected against lethal liver injury. RNA sequencing analysis revealed that EcN-HT rescued the global gene expression pattern in the livers of Fah-KO mice, particularly of genes involved in metabolic signaling and liver homeostasis. Moreover, EcN-HT treatment was found to be safe and well-tolerated in the mouse intestine. CONCLUSIONS: This is the first report of an engineered live bacterium that can degrade tyrosine and alleviate lethal liver injury in mice with HT1. EcN-HT represents a novel engineered probiotic with the potential to treat this condition. IMPACT AND IMPLICATIONS: Patients with hereditary tyrosinemia type 1 (HT1) are characterized by an inability to metabolize tyrosine normally and suffer from liver failure, renal dysfunction, neurological impairments, and cancer. Given the overlap and complementarity between the host and microbial metabolic pathways, the gut microbiome provides a potential chance to regulate host metabolism through degradation of tyrosine and reduction of byproducts that might be toxic. Herein, we demonstrated that an engineered live bacterium, EcN-HT, could enhance tyrosine breakdown, reduce the accumulation of toxic tyrosine byproducts, and protect against lethal liver injury in Fah-knockout mice. These findings suggested that engineered live biotherapeutics that can degrade tyrosine in the gut may represent a viable and safe strategy for the prevention of lethal liver injury in HT1 as well as the mitigation of its associated pathologies.

Efficacy and safety of tislelizumab plus lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma: a multicenter, single-arm, phase 2 trial.

BACKGROUND: Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. METHODS: In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; < 60 kg: 8 mg; once daily). Dose-limiting toxicities (DLTs) were evaluated in safety run-in phase to determine whether to enter the expansion phase. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Based on Simon's two-stage design, > 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy. RESULTS: Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6-51.9) and 90.3% (56/62, 95% CI, 80.1-96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8-not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7-94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients. CONCLUSIONS: Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04401800).

Prototype development and evaluation of a hyperspectral lidar optical receiving system.

As a new type of active Earth observation technology, airborne hyperspectral lidar combines the advantages of traditional lidar 3D information acquisition and passive hyperspectral imaging technology, and it can achieve integrated imaging detection with a high spatial and hyperspectral resolution. Thus, it has become an important future direction of Earth surface remote sensing technology. This article introduces the design and development of an airborne hyperspectral imaging lidar system. The hyperspectral lidar adopts a focal plane splitting method, combined with an array of 168 optical fibers, to couple wide-spectral-range laser echo signals one by one to the corresponding single tube detector, achieving efficient splitting and precise coupling of supercontinuum laser pulse echo signals. This article proposes a fast synchronous calibration method that is suitable for hyperspectral imaging lidar systems. Results show that the spectral range of the hyperspectral lidar system is 400-900 nm, and the spectral resolution of single-fiber detection is greater than 3 nm. Notably, this article focuses on analyzing the abnormal detection channels based on the calibration results. With the test results of adjacent channels combined, the reason for the abnormal spectral bandwidth of channel 17 is analyzed as an example. This research points out the direction for verifying the design parameters of the hyperspectral lidar prototype and lays an important foundation for airborne flight test of the hyperspectral lidar.

Magnetic-free polarization rotation in an atomic vapor cell.

Magnetic-free nonreciprocal optical devices have attracted great attention in recent years. Here, we investigated the magnetic-free polarization rotation of light in an atom vapor cell. Two mechanisms of magnetic-free nonreciprocity have been realized in ensembles of hot atoms, including electromagnetically induced transparency and optically-induced magnetization. For a linearly polarized input probe light, a rotation angle up to 86.4° has been realized with external control and pump laser powers of 10 mW and is mainly attributed to the optically-induced magnetization effect. Our demonstration offers a new approach to realize nonreciprocal devices, which can be applied to solid-state atom ensembles and may be useful in photonic integrated circuits.

Speed-enhanced scattering compensation method with sub-Nyquist sampling.

A rapid feedback-based scattering compensation method is particularly important for guiding light precisely within turbid tissues, especially the dynamic tissues. However, the huge number of measurements that come from the underutilization of the signal frequency channel greatly limits the modulation speed. This paper introduces a rapid compensation method with the sub-Nyquist sampling which improves the channel utilization and the speed of wavefront shaping. The number of measurements is reduced to ∼1500 with 32 × 32 freedom, and the PBR of the focus reaches ∼200. The system performances are demonstrated by focusing the light through brain slices of different thicknesses.

DY131 activates ERRγ/TFAM axis to protect against metabolic disorders and acute kidney injury.

Renal tubular injury is considered as the main pathological feature of acute kidney injury (AKI), and mitochondrial dysfunction in renal tubular cells is implicated in the pathogenesis of AKI. The estrogen-related receptor γ (ERRγ) is a member of orphan nuclear receptors which plays a regulatory role in mitochondrial biosynthesis, energy metabolism and many metabolic pathways. Online datasets showed a dominant expression of ERRγ in renal tubules, but the role of ERRγ in AKI is still unknown. In the present study, we investigated the role of ERRγ in the pathogenesis of AKI and the therapeutic efficacy of ERRγ agonist DY131 in several murine models of AKI. ERRγ expression was reduced in kidneys of AKI patients and AKI murine models along with a negative correlation to the severity of AKI. Consistently, silencing ERRγ in vitro enhanced cisplatin-induced tubular cells apoptosis, while ERRγ overexpression in vivo utilizing hydrodynamic-based tail vein plasmid delivery approach alleviated cisplatin-induced AKI. ERRγ agonist DY131 could enhance the transcriptional activity of ERRγ and ameliorate AKI in various murine models. Moreover, DY131 attenuated the mitochondrial dysfunction of renal tubular cells and metabolic disorders of kidneys in AKI, and promoted the expression of the mitochondrial transcriptional factor A (TFAM). Further investigation showed that TFAM could be a target gene of ERRγ and DY131 might ameliorate AKI by enhancing ERRγ-mediated TFAM expression protecting mitochondria. These findings highlighted the protective effect of DY131 on AKI, thus providing a promising therapeutic strategy for AKI.

Glycemic Status and Myocardial Strain by Cardiac MRI in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: It is uncertain how various degree of glycemic status affect left ventricular (LV) myocardial strain in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). PURPOSE: To investigate the relationship of glycemic status and myocardial strain in STEMI patients. STUDY TYPE: Prospective cohort study. POPULATION: 282 STEMI patients with cardiac magnetic resonance imaging 5 ± 2 days post-PPCI. Patients were divided into three groups based on the level of glycated hemoglobin A1c (HbA1c) (group 1: HbA1c < 5.7%; group 2: 5.7% ≤ HbA1c < 6.5%; group 3: HbA1c ≥ 6.5%). FIELD STRENGTH/SEQUENCE: 3.0-T; late gadolinium enhancement, balanced steady-state free precession cine sequence, black blood fat-suppressed T2-weighted. ASSESSMENT: LV function, myocardial strain, and infarct characteristics (infarct size, microvascular obstruction, and intramyocardial hemorrhage) were compared among the three groups by one-way analysis of variance (ANOVA) or Wilcoxon rank sum test. Intraobserver and interobserver reproducibility of LV myocardial strain was evaluated. STATISTICAL TESTS: ANOVA or Wilcoxon rank sum test, Pearson chi-square or Fisher's exact test, Spearman's correlation analyses and multivariable linear regression analysis. A two-tailed P value <0.05 was considered statistically significant. RESULTS: Infarct characteristics were similar among the three groups (P = 0.934, P = 0.097, P = 0.533, respectively). Patients with HbA1c ≥ 6.5% had decreased LV myocardial strain compared with HbA1c 5.7%-6.4%, as evidenced by global radial (GRS), global circumferential (GCS), and global longitudinal (GLS) strain. However, no significant differences in myocardial strain were observed between patients with HbA1c 5.7%-6.4% and HbA1c < 5.7% (P = 0.716; P = 0.294; P = 0.883, respectively). After adjustment for confounders, HbA1c as a continuous variable (beta coefficient [ß] = -0.676; ß = 0.172; ß = 0.205, respectively) and HbA1c ≥ 6.5% (ß = -3.682; ß = 0.552; ß = 0.681, respectively) were both independently associated with decreased GRS, GCS, and GLS. DATA CONCLUSION: Patients with uncontrolled blood glucose (categorized in group HbA1c ≥ 6.5%) had worse myocardial strain. The level of HbA1c appeared to be independently associated with decreased myocardial strain in STEMI patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Prognostic Impact of Neoadjuvant Chemotherapy in Localized or Locoregionally Advanced Gallbladder Cancer: A Population-Based and Propensity Score Matched SEER Analysis.

BACKGROUND: The effect of neoadjuvant chemotherapy (NACT) in gallbladder cancer (GBC) patients remains controversial. The aim of this study was to assess the impact of NACT on overall survival (OS) and cancer specific survival (CSS) in patients with localized or locoregionally advanced GBC, and to explore possible protective predictors for prognosis. METHODS: Data for patients with localized or locoregionally advanced GBC (i.e., categories cTx-cT4, cN0-2, and cM0) from 2004 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the NACT and non-NACT groups were propensity score matched (PSM) 1:3, and the Kaplan-Meier method and log-rank test were performed to analyze the impact of NACT on OS and CSS. Univariable and multivariable Cox regression models were applied to identify the possible prognostic factors. Subgroup analysis was conducted to identify patients who would benefit from NACT. RESULTS: Of the 2676 cases included, 78 NACT and 234 non-NACT patients remained after PSM. In localized or locoregionally advanced GBC patients, the median OS of the NACT and non-NACT was 31 and 16 months (log-rank P < 0.01), and the median CSS of NACT and non-NACT was 32 and 17 months (log-rank P < 0.01), respectively. Longer median OS (31 vs 17 months, log-rank P < 0.01) and CSS (32 vs 20 months, log-rank P < 0.01) was associated with NACT compared with surgery alone. Multivariable Cox regression analysis showed that NACT, stage, and surgery type were prognostic factors for OS and CSS in GBC patients. Subgroup analysis revealed that the survival hazard ratios (HRs) of NACT vs non-NACT for localized or locoregionally advanced GBC patients were significant in most subgroups. CONCLUSIONS: NACT may provide therapeutic benefits for localized or locoregionally advanced GBC patients, especially for those with advanced stage, node-positive, poorly differentiated or undifferentiated disease. NACT combined with radical surgery was associated with a survival advantage. Therefore, NACT combined with surgery may provide a better treatment option for resectable GBC patients.

Chiral Metal-Organic Frameworks.

In the past two decades, metal-organic frameworks (MOFs) or porous coordination polymers (PCPs) assembled from metal ions or clusters and organic linkers via metal-ligand coordination bonds have captivated significant scientific interest on account of their high crystallinity, exceptional porosity, and tunable pore size, high modularity, and diverse functionality. The opportunity to achieve functional porous materials by design with promising properties, unattainable for solid-state materials in general, distinguishes MOFs from other classes of materials, in particular, traditional porous materials such as activated carbon, silica, and zeolites, thereby leading to complementary properties. Scientists have conducted intense research in the production of chiral MOF (CMOF) materials for specific applications including but not limited to chiral recognition, separation, and catalysis since the discovery of the first functional CMOF (i.e., d- or l-POST-1). At present, CMOFs have become interdisciplinary between chirality chemistry, coordination chemistry, and material chemistry, which involve in many subjects including chemistry, physics, optics, medicine, pharmacology, biology, crystal engineering, environmental science, etc. In this review, we will systematically summarize the recent progress of CMOFs regarding design strategies, synthetic approaches, and cutting-edge applications. In particular, we will highlight the successful implementation of CMOFs in asymmetric catalysis, enantioselective separation, enantioselective recognition, and sensing. We envision that this review will provide readers a good understanding of CMOF chemistry and, more importantly, facilitate research endeavors for the rational design of multifunctional CMOFs and their industrial implementation.

Incidence and risk of remnant gastric cancer after gastrectomy for gastric cancer: a population-based study from the SEER database.

BACKGROUND: Gastric cancer (GC) constitutes a major global health problem, of which remnant gastric cancer (RGC) occurs less frequently. The rate of RGCs after gastrectomy for GC is increasing recently due to improved survival and screening, however, their incidence and risk have not been reported in the U.S. POPULATION: The objective of this study was to evaluate the incidence and elevated risk of RGC after GC gastrectomy in this population, and to identify the risk factors. METHODS: Patients underwent gastrectomy for first primary GC in 2000-2015 and those who developed RGC were identified from Surveillance, Epidemiology and End Results (SEER) database. Fine-Gray regression was used to estimate the cumulative incidence and to identify risk factors. Standardized incidence ratios (SIRs) were calculated by Poisson regression to compare the risk with the general population. RESULTS: Among 21,566 patients included in the cohort, 227 developed RGC. The 20-year cumulative incidence of RGC was 1.88%. Multivariate analysis revealed that older age, invasion depth, male sex, marital status, and lower income are independent risk factors for RGC development. SIR was 7.70 overall and > 4.5 in each stratum. CONCLUSIONS: Cumulative incidence and risk for RGCs increased continuously in patients underwent GC gastrectomy. Close and lifelong endoscopy surveillance should be recommended for patients who received GC gastrectomy, especially those with high-risk factors.

Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: Multicenter, real-world study.

AIM: The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents. METHODS: Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed. RESULTS: The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5 months (95% confidence interval [CI], 8.1-12.9) and 6.0 months (95% CI, 5.1-6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin-bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05-2.34; p = 0.028), tumor number (>3 vs. 1-3, HR 2.18; 95% CI, 1.10-4.34; p = 0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06-2.45; p = 0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37-0.83; p = 0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17-0.53; p < 0.001). Grade 3-4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed. CONCLUSIONS: Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment.

Artificial intelligence-aided diagnostic imaging: A state-of-the-art technique in precancerous screening.

BACKGROUND AND AIM: Chromoendoscopy with the use of indigo carmine (IC) dye is a crucial endoscopic technique to identify gastrointestinal neoplasms. However, its performance is limited by the endoscopist's skill, and no standards are available for lesion identification. Thus, we developed an artificial intelligence (AI) model to replace chromoendoscopy. METHODS: This pilot study assessed the feasibility of our novel AI model in the conversion of white-light images (WLI) into virtual IC-dyed images based on a generative adversarial network. The predictions of our AI model were evaluated against the assessments of five endoscopic experts who were blinded to the purpose of this study with a staining quality rating from 1 (unacceptable) to 4 (excellent). RESULTS: The AI model successfully transformed the WLI of polyps with different morphologies and different types of lesions in the gastrointestinal tract into virtual IC-dyed images. The quality ratings of the real IC-dyed and AI images did not significantly differ concerning surface structure (AI vs IC: 3.08 vs 3.00), lesion border (3.04 vs 2.98), and overall contrast (3.14 vs 3.02) from 10 sets of images (10 AI images and 10 real IC-dyed images). Although the score depended significantly on the evaluator, the staining methods (AI or real IC) and evaluators had no significant interaction (P > 0.05) with each other. CONCLUSION: Our results demonstrated the feasibility of employing AI model's virtual IC staining, increasing the possibility of being employed in daily practice. This novel technology may facilitate gastrointestinal lesion identification in the future.

Hearing protection field attenuation estimation systems and associated training for reducing workers' exposure to noise.

BACKGROUND: Global Burden of Disease studies identify hearing loss as the third leading cause of years lived with a disability. Their estimates point to large societal and individual costs from unaddressed hearing difficulties. Workplace noise is an important modifiable risk factor; if addressed, it could significantly reduce the global burden of disease. In practice, providing hearing protection devices (HPDs) is the most common intervention to reduce noise exposure at work. However, lack of fit of HPDs, especially earplugs, can greatly limit their effectiveness. This may be the case for 40% of users. Testing the fit and providing instructions to improve noise attenuation might be effective. In the past two decades, hearing protection fit-test systems have been developed and evaluated in the field. They are called field attenuation estimation systems. They measure the noise attenuation obtained by individual workers using HPDs. If there is a lack of fit, instruction for better fit is provided, and may lead to better noise attenuation obtained by HPDs. OBJECTIVES: To assess: (1) the effects of field attenuation estimation systems and associated training on the noise attenuation obtained by HPDs compared to no instruction or to less instruction in workers exposed to noise; and (2) whether these interventions promote adherence to HPD use. SEARCH METHODS: We used CENTRAL, MEDLINE, five other databases, and two trial registers, together with reference checking, citation searching, and contact with study authors to identify studies. We imposed no language or date restrictions. The latest search date was February 2024. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-RCTs, controlled before-after studies (CBAs), and interrupted time-series studies (ITSs) exploring HPD fit testing in workers exposed to noise levels of more than 80 A-weighted decibels (or dBA) who use hearing protection devices. The unit 'dBA' reports on the use of a frequency-weighting filter to adjust sound measurement results to better reflect how human ears process sound. The outcome noise attenuation had to be measured either as a personal attenuation rating (PAR), PAR pass rate, or both. PAR pass rate is the percentage of workers who passed a pre-established level of sufficient attenuation from their HPDs, identified on the basis of their individual noise exposure. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, risk of bias, and extracted data. We categorised interventions as fit testing of HPDs with instructions at different levels (no instructions, simple instructions, and extensive instructions). MAIN RESULTS: We included three RCTs (756 participants). We did not find any studies that examined whether fit testing and training contributed to hearing protector use, nor any studies that examined whether age, gender, or HPD experience influenced attenuation. We would have included any adverse effects if mentioned by the trial authors, but none reported them. None of the included studies blinded participants; two studies blinded those who delivered the intervention. Effects of fit testing of HPDs with instructions (simple or extensive) versus fit testing of HPDs without instructions Testing the fit of foam and premoulded earplugs accompanied by simple instructions probably does not improve their noise attenuation in the short term after the test (1-month follow-up: mean difference (MD) 1.62 decibels (dB), 95% confidence interval (CI) -0.93 to 4.17; 1 study, 209 participants; 4-month follow-up: MD 0.40 dB, 95% CI -2.28 to 3.08; 1 study, 197 participants; both moderate-certainty evidence). The intervention probably does not improve noise attenuation in the long term (MD 0.15 dB, 95% CI -3.44 to 3.74; 1 study, 103 participants; moderate-certainty evidence). Fit testing of premoulded earplugs with extensive instructions on the fit of the earplugs may improve their noise attenuation at the immediate retest when compared to fit testing without instructions (MD 8.34 dB, 95% CI 7.32 to 9.36; 1 study, 100 participants; low-certainty evidence). Effects of fit testing of HPDs with extensive instructions versus fit testing of HPDs with simple instructions Fit testing of foam earplugs with extensive instructions probably improves their attenuation (MD 8.62 dB, 95% CI 6.31 to 10.93; 1 study, 321 participants; moderate-certainty evidence) and also the pass rate of sufficient attenuation (risk ratio (RR) 1.75, 95% CI 1.44 to 2.11; 1 study, 321 participants; moderate-certainty evidence) when compared to fit testing with simple instructions immediately after the test. This is significant because every 3 dB decrease in noise exposure level halves the sound energy entering the ear. No RCTs reported on the long-term effectiveness of the HPD fit testing with extensive instructions. AUTHORS' CONCLUSIONS: HPD fit testing accompanied by simple instructions probably does not improve noise attenuation from foam and premoulded earplugs. Testing the fit of foam and premoulded earplugs with extensive instructions probably improves attenuation and PAR pass rate immediately after the test. The effects of fit testing associated with training to improve attenuation may vary with types of HPDs and training methods. Better-designed trials with larger sample sizes are required to increase the certainty of the evidence.

Cylinder power progression associated with axial length in young children: a two-year follow-up study.

PURPOSE: To describe the association of refraction development and axial length (AL) in young children and provide new insights into the progression of cylinder power. METHODS: Children (2-3 grades) were enrolled from primary schools in Shanghai and followed up for two years. Cycloplegic refraction, AL, and corneal curvature radius were measured. Refraction parameters were compared among groups with different AL, AL1 (AL < 23.5 mm), AL2 (23.5 mm ≤ AL < 24.5 mm), and AL3 (AL ≥ 24.5 mm). Multiple regression analysis was used to explore risk factors of diopter of cylinder (DC) progression. RESULTS: In total, out of 6891 enrolled children, 5961 participants (7-11 yrs) were included in the final analysis. Over the two-year period, the cylinder power significantly changed, and those with longer AL had more rapid DC progression over the two years (AL1, -0.09 ± 0.35 D; AL2, -0.15 ± 0.39 D; AL3, -0.29 ± 0.44 D) (P < 0.001). The change in DC was independently associated with AL at baseline (P < 0.001). The proportion of with-the-rule astigmatism increased from 91.3% to 92.1% in AL1 group, from 89.1% to 91.8% in AL2 group and from 87.1% to 92.0% in AL3 group. CONCLUSIONS: Young children with long AL experienced rapid progression of cylinder power. Both the control of myopia progression and attention to the correction of astigmatism are necessary in the health management of children with long AL. The significantly increased AL in participants might contribute to both the extent and direction of astigmatism.

Evaluation of deep learning-based reconstruction late gadolinium enhancement images for identifying patients with clinically unrecognized myocardial infarction.

BACKGROUND: The presence of infarction in patients with unrecognized myocardial infarction (UMI) is a critical feature in predicting adverse cardiac events. This study aimed to compare the detection rate of UMI using conventional and deep learning reconstruction (DLR)-based late gadolinium enhancement (LGEO and LGEDL, respectively) and evaluate optimal quantification parameters to enhance diagnosis and management of suspected patients with UMI. METHODS: This prospective study included 98 patients (68 men; mean age: 55.8 ± 8.1 years) with suspected UMI treated at our hospital from April 2022 to August 2023. LGEO and LGEDL images were obtained using conventional and commercially available inline DLR algorithms. The myocardial signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and percentage of enhanced area (Parea) employing the signal threshold versus reference mean (STRM) approach, which correlates the signal intensity (SI) within areas of interest with the average SI of normal regions, were analyzed. Analysis was performed using the standard deviation (SD) threshold approach (2SD-5SD) and full width at half maximum (FWHM) method. The diagnostic efficacies based on LGEDL and LGEO images were calculated. RESULTS: The SNRDL and CNRDL were two times better than the SNRO and CNRO, respectively (P < 0.05). Parea-DL was elevated compared to Parea-O using the threshold methods (P < 0.05); however, no intergroup difference was found based on the FWHM method (P > 0.05). The Parea-DL and Parea-O also differed except between the 2SD and 3SD and the 4SD/5SD and FWHM methods (P < 0.05). The receiver operating characteristic curve analysis revealed that each SD method exhibited good diagnostic efficacy for detecting UMI, with the Parea-DL having the best diagnostic efficacy based on the 5SD method (P < 0.05). Overall, the LGEDL images had better image quality. Strong diagnostic efficacy for UMI identification was achieved when the STRM was ≥ 4SD and ≥ 3SD for the LGEDL and LGEO, respectively. CONCLUSIONS: STRM selection for LGEDL magnetic resonance images helps improve clinical decision-making in patients with UMI. This study underscored the importance of STRM selection for analyzing LGEDL images to enhance diagnostic accuracy and clinical decision-making for patients with UMI, further providing better cardiovascular care.