Development of an artificial intelligent model for pre-endoscopic screening of precancerous lesions in gastric cancer.

BACKGROUND: Given the high cost of endoscopy in gastric cancer (GC) screening, there is an urgent need to explore cost-effective methods for the large-scale prediction of precancerous lesions of gastric cancer (PLGC). We aim to construct a hierarchical artificial intelligence-based multimodal non-invasive method for pre-endoscopic risk screening, to provide tailored recommendations for endoscopy. METHODS: From December 2022 to December 2023, a large-scale screening study was conducted in Fujian, China. Based on traditional Chinese medicine theory, we simultaneously collected tongue images and inquiry information from 1034 participants, considering the potential of these data for PLGC screening. Then, we introduced inquiry information for the first time, forming a multimodality artificial intelligence model to integrate tongue images and inquiry information for pre-endoscopic screening. Moreover, we validated this approach in another independent external validation cohort, comprising 143 participants from the China-Japan Friendship Hospital. RESULTS: A multimodality artificial intelligence-assisted pre-endoscopic screening model based on tongue images and inquiry information (AITonguequiry) was constructed, adopting a hierarchical prediction strategy, achieving tailored endoscopic recommendations. Validation analysis revealed that the area under the curve (AUC) values of AITonguequiry were 0.74 for overall PLGC (95% confidence interval (CI) 0.71-0.76, p < 0.05) and 0.82 for high-risk PLGC (95% CI 0.82-0.83, p < 0.05), which were significantly and robustly better than those of the independent use of either tongue images or inquiry information alone. In addition, AITonguequiry has superior performance compared to existing PLGC screening methodologies, with the AUC value enhancing 45% in terms of PLGC screening (0.74 vs. 0.51, p < 0.05) and 52% in terms of high-risk PLGC screening (0.82 vs. 0.54, p < 0.05). In the independent external verification, the AUC values were 0.69 for PLGC and 0.76 for high-risk PLGC. CONCLUSION: Our AITonguequiry artificial intelligence model, for the first time, incorporates inquiry information and tongue images, leading to a higher precision and finer-grained pre-endoscopic screening of PLGC. This enhances patient screening efficiency and alleviates patient burden.

The Effect of Physical Therapy on Somatosensory Tinnitus.

Objective: The objective of this work was to assess the effect of physical therapy in patients with somatosensory tinnitus (ST) and explore the influence of physical therapy on clinical variables obtained before treatment. Methods: A total of 43 patients with ST were randomized to the immediate-start group (n = 20) and delayed-start group (n = 23). All patients received physical therapy for 1 week (seven sessions). Each session lasted 60 min. The Visual Analogue Scale (VAS), Tinnitus Handicap Inventory (THI), and numerical pain rating scale (NPRS) scores were documented at baseline and after treatment (week 1) for all patients. For subjects in the immediate-start group, the THI, VAS, and NPRS scores were measured after therapy (weeks 6, 9, and 12, respectively). Medical history characteristic functional activity scale (HCFA) scores were measured at baseline to assess the association between somatic symptoms and tinnitus. Results: At week 1, VAS, THI, and NPRS scores of patients in the immediate-start group were improved by 1.25 ± 1.59, 11.10 ± 15.10, and 0.95 ± 1.54 points, respectively, and were significantly higher than those in the delayed-start group (p < 0.05). The change in VAS, THI, and NPRS scores in the treatment group was significantly positively correlated with the scores of the HCFA before treatment (r = 0.786, p < 0.001; r = 0.680, p = 0.001; r = 0.796, p < 0.001). There was no significant difference in THI, VAS, and NPRS scores among patients in the immediate-start group between weeks 1, 6, 9, and 12 after treatment (p > 0.05). Conclusions: Although more participants were necessary in the further study, the study implies that physical therapy can reduce physical pain, improve tinnitus symptoms, and quality of life in ST patients without hearing loss, and the short-term curative effect is stable, especially for tinnitus patients with clear somatic symptoms.

Blockade of the ADAM8-Fra-1 complex attenuates neuroinflammation by suppressing the Map3k4/MAPKs axis after spinal cord injury.

BACKGROUND: Mechanical spinal cord injury (SCI) is a deteriorative neurological disorder, causing secondary neuroinflammation and neuropathy. ADAM8 is thought to be an extracellular metalloproteinase, which regulates proteolysis and cell adherence, but whether its intracellular region is involved in regulating neuroinflammation in microglia after SCI is unclear. METHODS: Using animal tissue RNA-Seq and clinical blood sample examinations, we found that a specific up-regulation of ADAM8 in microglia was associated with inflammation after SCI. In vitro, microglia stimulated by HMGB1, the tail region of ADAM8, promoted microglial inflammation, migration and proliferation by directly interacting with ERKs and Fra-1 to promote activation, then further activated Map3k4/JNKs/p38. Using SCI mice, we used BK-1361, a specific inhibitor of ADAM8, to treat these mice. RESULTS: The results showed that administration of BK-1361 attenuated the level of neuroinflammation and reduced microglial activation and recruitment by inhibiting the ADAM8/Fra-1 axis. Furthermore, treatment with BK-1361 alleviated glial scar formation, and also preserved myelin and axonal structures. The locomotor recovery of SCI mice treated with BK-1361 was therefore better than those without treatment. CONCLUSIONS: Taken together, the results showed that ADAM8 was a critical molecule, which positively regulated neuroinflammatory development and secondary pathogenesis by promoting microglial activation and migration. Mechanically, ADAM8 formed a complex with ERK and Fra-1 to further activate the Map3k4/JNK/p38 axis in microglia. Inhibition of ADAM8 by treatment with BK-1361 decreased the levels of neuroinflammation, glial formation, and neurohistological loss, leading to favorable improvement in locomotor functional recovery in SCI mice.

Switchable Single- to Multiwavelength Conventional Soliton and Bound-State Soliton Generated from a NbTe2 Saturable Absorber-Based Passive Mode-Locked Erbium-Doped Fiber Laser.

As a member of transition metal dichalcogenides (TMDs), NbTe2 has a work function of 5.32 eV and a band gap of 0 eV at the Fermi level, which enables it to possess broadband absorption characteristics and has huge potential in optoelectronic devices. In this work, a combination of liquid phase exfoliation (LPE) and optical deposition methods (ODMs) were used to fabricate a NbTe2 saturable absorber (SA). Based on the NbTe2 SA, a ring passive mode-locked erbium-doped fiber laser (PML-EDFL) was constructed by adding NbTe2 SA into the laser cavity. A switchable single- to multiwavelength (dual/triple/quadruple) conventional soliton (CS) and a bound-state soliton (BS) were observed for the first time. The results reveal that NbTe2 SA has excellent saturable absorption characteristics (modulation depth of 2.6%, saturation intensity of 177.4 MW/cm2, and unsaturated loss of 63.8%) and can suppress mode competition and stabilize multiwavelength oscillation. This study expands the applications of NbTe2 nanosheets in ultrafast optoelectronics. The proposed switchable PML-EDFL has extensive applications in high-capacity all-optical communication, high-sensitivity optical fiber sensing, high-precision spectral measurements, and high-energy-efficiency photon neural networks.

Evaluation of the inhibitory effects of antigout drugs on human carboxylesterases in vitro.

Gout is an immune-metabolic disease that frequently coexists with multiple comorbidities such as chronic kidney disease, cardiovascular disease and metabolic syndrome, therefore, it is often treated in combination with these complications. The present study aimed to evaluate the inhibitory effect of antigout drugs (allopurinol, febuxostat, topiroxostat, benzbromarone, lesinurad and probenecid) on the activity of the crucial phase I drug-metabolizing enzymes, carboxylesterases (CESs). 2-(2-benzoyl-3-methoxyphenyl) benzothiazole (BMBT) and fluorescein diacetate (FD) were utilized as the probe reactions to determine the activity of CES1 and CES2, respectively, through in vitro culturing with human liver microsomes. Benzbromarone and lesinurad exhibited strong inhibition towards CESs with Ki values of 2.16 and 5.15 µM for benzbromarone towards CES1 and CES2, respectively, and 2.94 µM for lesinurad towards CES2. In vitro-in vivo extrapolation (IVIVE) indicated that benzbromarone and lesinurad might disturb the metabolic hydrolysis of clinical drugs in vivo by inhibiting CESs. In silico docking showed that hydrogen bonds and hydrophobic interactions contributed to the intermolecular interactions of antigout drugs on CESs. Therefore, vigilant monitoring of potential drug-drug interactions (DDIs) is imperative when co-administering antigout drugs in clinical practice.

HM_ADET: a hybrid model for automatic detection of eyelid tumors based on photographic images.

BACKGROUND: The accurate detection of eyelid tumors is essential for effective treatment, but it can be challenging due to small and unevenly distributed lesions surrounded by irrelevant noise. Moreover, early symptoms of eyelid tumors are atypical, and some categories of eyelid tumors exhibit similar color and texture features, making it difficult to distinguish between benign and malignant eyelid tumors, particularly for ophthalmologists with limited clinical experience. METHODS: We propose a hybrid model, HM_ADET, for automatic detection of eyelid tumors, including YOLOv7_CNFG to locate eyelid tumors and vision transformer (ViT) to classify benign and malignant eyelid tumors. First, the ConvNeXt module with an inverted bottleneck layer in the backbone of YOLOv7_CNFG is employed to prevent information loss of small eyelid tumors. Then, the flexible rectified linear unit (FReLU) is applied to capture multi-scale features such as texture, edge, and shape, thereby improving the localization accuracy of eyelid tumors. In addition, considering the geometric center and area difference between the predicted box (PB) and the ground truth box (GT), the GIoU_loss was utilized to handle cases of eyelid tumors with varying shapes and irregular boundaries. Finally, the multi-head attention (MHA) module is applied in ViT to extract discriminative features of eyelid tumors for benign and malignant classification. RESULTS: Experimental results demonstrate that the HM_ADET model achieves excellent performance in the detection of eyelid tumors. In specific, YOLOv7_CNFG outperforms YOLOv7, with AP increasing from 0.763 to 0.893 on the internal test set and from 0.647 to 0.765 on the external test set. ViT achieves AUCs of 0.945 (95% CI 0.894-0.981) and 0.915 (95% CI 0.860-0.955) for the classification of benign and malignant tumors on the internal and external test sets, respectively. CONCLUSIONS: Our study provides a promising strategy for the automatic diagnosis of eyelid tumors, which could potentially improve patient outcomes and reduce healthcare costs.

A Novel COCH p.D544Vfs*3 Variant Associated with DFNA9 Sensorineural Hearing Loss Causes Pathological Multimeric Cochlin Formation.

COCH (coagulation factor C homology) is one of the most frequently mutated genes of autosomal dominant non-syndromic hearing loss. Variants in COCH could cause DFNA9, which is characterized by late-onset hearing loss with variable degrees of vestibular dysfunction. In this study, we report a Chinese family with a novel COCH variant (c.1687delA) causing p.D544Vfs*3 in the cochlin. Comprehensive audiometric tests and vestibular function assessments were taken to acquire the phenotypic profile of the subjects. Next-generation sequencing was conducted and segregation analysis was carried out using Sanger sequencing. The proband presented mild vestibular symptoms and normal functional assessment results in almost every test, while the variant co-segregated with hearing impairment in the pedigree. The variant was located beyond the vWFA2 domain, which was predicted to affect the post-translational cleavage of the cochlin via molecular modeling analysis. Notably, in the overexpressing study, by transient transfecting the HEK 293T cells, we found that the p.D544Vfs*3 variant increased the formation of multimeric cochlin. Our result enriched the spectrum of DFNA9-linked pathological COCH variants and suggested that variants, causative of cochlin multimerization, could be related to DFNA9 with sensorineural hearing loss rather than serious vestibular symptoms.