Hypoglossal-nerve stimulation (HGNS) is an established second-line therapy for patients with obstructive sleep apnea (OSA). Existing studies investigating the effect of preoperative drug-induced sleep endoscopic (DISE) findings on HGNS outcomes have mainly focused on the apnea/hypopnea index (AHI) among polysomnography (PSG) parameters, and have less frequently tested other PSG parameters such as the apnea index (AI), hypopnea index (HI), oxygen desaturation index (ODI), snoring index, and arousal index, or patient-reported excessive daytime sleepiness. The aim of this study was to investigate the correlation between DISE findings and the above-mentioned metrics after HGNS therapy. We only included patients with DISE findings providing detailed information about the degree of the anteroposterior velar (APV), oropharyngeal lateral wall (OPLW), or tongue-base (BT) obstruction based on the velum, oropharynx, base of tongue, and epiglottis (VOTE) classification. The data of 25 patients (9 female (36%)) were retrospectively evaluated. The mean age at the date of implantation was 54.52 ± 9.61 years, and the mean BMI was 29.99 ± 3.97 kg/m². Spearman’s rho correlation coefficients were calculated. Significant correlations were found between the degree of APV obstruction and postoperative HI (r = −0.5, p < 0.05), and between the degree of OPLW obstruction and postoperative snoring index (r = 0.42, p < 0.05). BT obstruction was strongly correlated with postoperative metrics such as AHI (r = −0.57, p < 0.01), AI (r = −0.5, p < 0.05), ODI (r = −0.57, p < 0.01), ∆ AHI (r = 0.58, p < 0.01), ∆ AI (r = 0.54, p < 0.01) and ∆ ODI (r = 0.54, p < 0.01). No significant correlation was found between DISE findings and postoperative Epworth Sleepiness Scale values. These findings suggest that preoperative DISE findings, especially the degree of BT obstruction, are important for predicting an HGNS therapy outcome. Full article

Background: The characteristic magnetic resonance imaging (MRI) and the positron emission tomography (PET) findings of PCNSL often overlap with other intracranial tumors, making definitive diagnosis challenging. PCNSL typically shows iso-hypointense to grey matter on T2-weighted imaging. However, a particular part of PCNSL can demonstrate T2-weighted hyperintensity as other intracranial tumors. Moreover, normal high uptake of FDG in the basal ganglia, thalamus, and grey matter can mask underlying PCNSL in ¹⁸F-FDG PET. In order to promote the efficiency of diagnosis, the MRI-based or PET/CT-based radiomics models combining histograms with texture features in diagnosing glioma and brain metastases have been widely established. However, the diagnosing model for PCNSL has not been widely reported. The study was designed to investigate a machine-learning (ML) model based on multiple parameters of 2-deoxy-2-[18F]-floor-D-glucose (¹⁸F-FDG) PET for differential diagnosis of PCNSL and metastases in the brain. Methods: Patients who underwent an ¹⁸F-FDG PET scan with untreated PCNSL or metastases in the brain were included between May 2016 and May 2022. A total of 126 lesions from 51 patients (43 patients with untreated brain metastases and eight patients with untreated PCNSL), including 14 lesions of PCNSL, and 112 metastatic lesions in the brain, met the inclusion criteria. PCNSL or brain metastasis was confirmed after pathology or clinical history. Principal component analysis (PCA) was used to decompose the datasets. Logistic regression (LR), support vector machine (SVM), and random forest classification (RFC) models were trained by two different groups of datasets, the group of multi-class features and the group of density features, respectively. The model with the highest mean precision score was selected. The testing sets and original data were used to examine the efficacy of models separately by using the weighted average F1 score and area under the curve (AUC) of the receiver operating characteristic curve (ROC). Results: The multi-class features-based RFC and SVM models reached identical weighted-average F1 scores in the testing set, and the score was 0.98. The AUCs of RFC and SVM models calculated from the testing set were 1.00 equally. Evaluated by the original dataset, the RFC model based on multi-class features performs better than the SVM model, whose weighted-average F1 scores of the RFC model calculated from the original data were 0.85 with an AUC of 0.93. Conclusions: The ML based on multi-class features of ¹⁸F-FDG PET exhibited the potential to distinguish PCNSL from brain metastases. The RFC models based on multi-class features provided comparatively high efficiency in our study. Full article

Angiogenesis is crucial in the development and progression of tumors. This study examined the relationship between angiogenesis-related lncRNAs (AR-lncRNAs) and breast cancer (BC) immunity and prognosis. We used univariate Cox regression analysis to obtain AR-lncRNAs closely related to BC prognosis. Cluster analysis of BC patients was performed using non-negative matrix factorization (NMF) analysis according to the expression of AR-lncRNAs that were prognostically relevant. An AR-lncRNA risk model (AR-lncM) was created using LASSO regression analysis to predict the prognosis and survival of BC patients. Subsequently, the effect of LINC01614 on cell migration and invasion was verified by Transwell and Western blot assays, and the CCK-8 assay detected its impact on cell sensitivity to tamoxifen. Finally, we obtained 17 AR-lncRNAs from the TCGA database that were closely associated with the prognosis of BC patients. Based on the expression of these AR-lncRNAs, BC patients were divided into five clusters using NMF analysis. Cluster 1 was found to have a better prognosis, higher expression of immune checkpoints, and higher levels of immune cell infiltration. Furthermore, an AR-LncM model was created using ten prognostic-related AR-lncRNAs. The model’s risk predictive performance was validated using survival analysis, timeROC curves, and univariate and multivariate Cox analysis. The most interesting gene in the model, LINC01614, was found to regulate epithelial-mesenchymal transition (EMT) and tamoxifen sensitivity in BC cells, implying that LINC01614 could be a potential therapeutic target for BC patients. Full article

Heart failure (HF) is classified according to the degree of reduction in left ventricular ejection fraction (EF) in HF with reduced, mildly reduced, and preserved EF. Biomarkers could behave differently depending on EF type. Here, we analyze the soluble form of the AXL receptor tyrosine kinase (sAXL) in HF patients with reduced and preserved EF. Two groups of HF patients with reduced (HFrEF; n = 134) and preserved ejection fraction (HFpEF; n = 134) were included in this prospective observational study, with measurements of candidate biomarkers and functional, clinical, and echocardiographic variables. A Cox regression model was used to determine predictors for clinical events: cardiovascular mortality and all-cause mortality. sAXL circulating values predicted outcome in HF: for a 1.0 ng/mL increase in serum sAXL, the mortality hazard ratio (HR) was 1.019 for HFrEF (95% CI 1.000 to 1.038) and 1.032 for HFpEF (95% CI 1.013 to 1.052). In a multivariable Cox regression analysis, sAXL and NT-proBNP were independent markers for all-cause and cardiovascular mortality in HFpEF. In contrast, only NT-proBNP remained significant in the HFrEF group. When analyzing the event-free survival at a mean follow-up of 3.6 years, HFrEF and HFpEF patients in the higher quartile of sAXL had a reduced survival time. Interestingly, sAXL is a reliable predictor for all-cause and cardiovascular mortality only in the HFpEF cohort. The results suggest an important role for AXL in HFpEF, supporting sAXL evaluation in larger clinical studies and pointing to AXL as a potential target for HF therapy. Full article

Deep learning models are usually utilized to learn from spatial data, only a few studies are proposed to predict glaucoma time progression utilizing deep learning models. In this article, we present a bidirectional recurrent deep learning model (Bi-RM) to detect prospective progressive visual field diagnoses. A dataset of 5413 different eyes from 3321 samples is utilized as the learning phase dataset and 1272 eyes are used for testing. Five consecutive diagnoses are recorded from the dataset as input and the sixth progressive visual field diagnosis is matched with the prediction of the Bi-RM. The precision metrics of the Bi-RM are validated in association with the linear regression algorithm (LR) and term memory (TM) technique. The total prediction error of the Bi-RM is significantly less than those of LR and TM. In the class prediction, Bi-RM depicts the least prediction error in all three methods in most of the testing cases. In addition, Bi-RM is not impacted by the reliability keys and the glaucoma degree. Full article

The aim of this 4-year observational study is to analyze the outcomes of stroke patients treated with direct mechanical thrombectomy (dMT) compared to bridging therapy (BT) (intravenous thrombolysis [IVT] + BT) based on 3-month outcomes, in real clinical practice in the "Stroke Belt" of Southern Europe. In total, 300 patients were included (41.3% dMT and 58.6% BT). The frequency of direct referral to the stroke center was similar in the dMT and BT group, whereas the time from onset to groin was longer in the BT group (median 210 [IQR 160–303] vs. 399 [IQR 225–675], p = 0.001). Successful recanalization (TICI 2b-3) and hemorrhagic transformation were similar in both groups. The BT group more frequently showed excellent outcomes at 3 months (32.4% vs. 15.4%, p = 0.004). Multivariate analysis showed that BT was independently associated with excellent outcomes (OR 2.7. 95% CI,1.2–5.9, p = 0.02) and lower mortality (OR 0.36. 95% CI 0.16–0.82, p = 015). Conclusions: Compared with dMT, BT was associated with excellent functional outcomes and lower 3-month mortality in this real-world clinical practice study conducted in a region belonging to the “Stroke Belt” of Southern Europe. Given the disparity of results on the benefit of BT in the current evidence, it is of vital importance to analyze the convenience of its use in each health area. Full article

Objective: Neuroinflammation is a major etiology of cognitive dysfunction due to sepsis. Maresin1 (MaR1), identified as a docosahexaenoic acid (DHA)-derived metabolite from macrophages, has been demonstrated to exhibit potent neuroprotective and anti-inflammatory effects. Nevertheless, detailed functions and molecular mechanism of MaR1 in sepsis-induced cognitive dysfunction has not been fully elucidated. Here, we aimed to investigate potential neuroprotective effects of MaR1 on microglia-induced neuroinflammation in sepsis-induced cognitive impairment and to explore its anti-inflammatory mechanism. Methods: Different doses of MaR1 were administered to septic rats by via tail vein injection. The optimal dose was determined based on the 7-day survival rate of rats from each group. derived from macrophages with both anti-inflammatory to observe the ameliorative effects of MaR1 at optimal doses on cognitive dysfunction in septic rats. The effects of MaR1 on neuroinflammation-mediated microglial activation, neuronal apoptosis, and pro-inflammatory cytokine productions were in vivo and in vitro assayed, using Western blot, ELISA, TUNEL staining, Nissl staining, and the immunofluorescence method. To further elucidate anti-inflammatory machinery of MaR1, protein expressions of NLRP3 inflammatory vesicles and TLR4-NF-κB pathway-related proteins were subjected to Western blot assay. Results: After tail vein injection of MaR1 with different doses (2 ng/g, 4 ng/g, 8 ng/g), the results showed that 4 ng/g MaR1 treatment significantly increased the rats’ 7-day survival rate compared to the CLP controls. Therefore, subsequent experiments set 4 ng/g MaR1 as the optimal dose. Morris water maze experiments confirmed that MaR1 significantly reduced space memory dysfunction in rats. In addition, in CLP rats and LPS-stimulated BV2 microglia, MaR1 significantly reduced activated microglia and pro-inflammatory cytokines levels and neuronal apoptosis. Mechanically, MaR1 inhibits microglia-induced neuroinflammation through suppressing activations of NLRP3 inflammatory vesicles and TLR4-NF-κB signal pathway. Conclusion: Collectively, our findings suggested that MaR1 might be a prospective neuroprotective compound for prevention and treatment in the sepsis process. Full article

Background. Improving intraoperative accuracy with a validated surgical biomarker is important because identifying high-grade areas within a glioma will aid neurosurgical decision-making and sampling. Methods. We designed a multicentre, prospective surgical cohort study (GALA-BIDD) to validate the presence of visible fluorescence as a pragmatic intraoperative surgical biomarker of suspected high-grade disease within a tumour mass in patients undergoing 5-aminolevulinic acid (5-ALA) fluorescence-guided cytoreductive surgery. Results. A total of 106 patients with a suspected high-grade glioma or malignant transformation of a low-grade glioma were enrolled. Among the 99 patients who received 5-ALA, 89 patients were eligible to assess the correlation of fluorescence with diagnosis as per protocol. Of these 89, 81 patients had visible fluorescence at surgery, and 8 patients had no fluorescence. A total of 80 out of 81 fluorescent patients were diagnosed as high-grade gliomas on postoperative central review with 1 low-grade glioma case. Among the eight patients given 5-ALA who did not show any visible fluorescence, none were high-grade gliomas, and all were low-grade gliomas. Of the seven patients suspected radiologically of malignant transformation of low-grade gliomas and with visible fluorescence at surgery, six were diagnosed with high-grade gliomas, and one had no tissue collected. Conclusion. In patients where there is clinical suspicion, visible 5-ALA fluorescence has clinical utility as an intraoperative surgical biomarker of high-grade gliomas and can aid surgical decision-making and sampling. Further studies assessing the use of 5-ALA to assess malignant transformation in all diffuse gliomas may be valuable. Full article

Objective: This study aims to analyze the biomechanical characteristics of tile B2 pelvic fractures using finite element analysis when the superior ramus of the pubis was fixed by a plate or hollow screws in standing and sitting positions, respectively. Methods: A three-dimensional digital model of the tile B2 pelvic fracture was obtained by CT scanning the patient. The main ligament structure was then reconstructed based on the anatomical characteristics to create a finite element model of the tile B2 pelvic fracture. The posterior pelvic ring was fixed by sacroiliac joint screws, while the anterior ring injury of the superior ramus of the pubis was fixed by plates and hollow compression screws, respectively. The degrees of freedom of the bilateral acetabulum or two sides of the ischial tuberosity were constrained in the two models. A vertical load of 600 N was applied to the upper surface of the sacrum to measure the displacement and stress distribution of the pelvis in the standing and sitting positions. Results: The displacement distribution of both the healthy and the affected side of the pelvis was relatively uniform in both the plate group and the hollow screw group according to the finite element simulation results. The maximum displacement value in the sitting position was greater than the standing position, and the maximum displacement value of the hollow screw fixation was greater than that of the plate fixation. In the four groups of fixation models, the maximum displacement value of the pelvis in the hollow screw sitting position group was 1616.80 × 10⁻³ mm, which was greater than that of the other three groups, and in this group the total displacement value of the hollow screw in the anterior ring was 556.31 × 10⁻³ mm. The stress distribution of the pelvis in the various models was similar in the four groups of models, in which the maximum stress of the pelvis in the hollow screw sitting position group was the largest, which was 201.33 MPa, while the maximum stress in the standing position was 149.85 MPa greater than that in the sitting position of the hollow screw fixation. Conclusion: The anterior ring of patients with Tile B2 pelvic fractures fixed with hollow screws or plates in both standing and sitting positions can achieve satisfactory biomechanical results with significant safety margins for plates and screws. Full article

Background: Perineal pain is a painful neuropathic condition, which does not have a standard diagnostic or treatment approach. As such, we sought to evaluate the global scientific output of research into perineal pain and explore trends from 1981 to 2021 using bibliometric methods. Methods: Articles on perineal pain were retrieved from the Web of Science (WoS) database. We analyzed the content and quality of publications from within the specified timeframe. We also utilized VOSviewer to mine and cluster data from retrieved articles. Results: A total of 1917 articles were collected. The number of related papers published increased year by year. Articles were most frequently published by authors in the United States and France. Although the US remains at the center of this field, publications from China have become more frequent in recent years. We also found that French academic institutions dominate the field of perineal pain, and Jean-Jacques Labat from Nantes Universite is the most published author in the field. “Episiotomy”, “pain”, “management”, “prostatectomy”, “pelvic pain”, and “complication” were frequently cited as keywords. Conclusion: The increasing number of publications each year indicates that perineal pain has gained more attention as an important research topic. Full article

Background: Giant cell arteritis (GCA) and Takayasu arteritis (TA) are distinct types of large-vessel vasculitis; however, the clinical features of the diseases have some similarities. Limited data are available regarding Japanese patients with GCA and TA. The present study aimed to compare the clinical features and outcomes of Japanese patients with GCA and TA and the effects of large vessel involvement (LVI). Methods: We performed a retrospective cohort study of the patients with GCA (n = 15) and TA (n = 30) who visited our department from April 2012 to June 2022. Signs and symptoms attributed to the disease, treatment, clinical outcomes, and mortality were recorded using a standardized database. Results: The median age of onset was significantly higher in the GCA group at 24 years (range, 16–72 years) in the TA group and 77 years (range, 57–89 years) in the GCA group (p < 0.001). There were no significant differences in survival rates or the cumulative rates of cardiovascular events between the GCA and TA groups. However, relapse-free survival rates were significantly higher in patients with GCA than in patients with TA. Seven of the 15 patients with GCA had large vessel involvement, which did not affect the survival rates. Prednisolone (PSL) doses were significantly decreased after induction therapy in both groups, and the rates of achieving steroid tapering (PSL < 5.0 mg/day) were significantly higher in patients with GCA compared with those in patients with TA. Conclusions: Our study demonstrated no significant difference in the survival rates of Japanese patients with GCA and TA. The relapse-free survival rates were significantly higher in the GCA group than in the TA group. LVI may not be associated with disease relapse or survival rate in Japanese patients with GCA. Full article

Immunoglobulin G4-related disease (IgG4-RD) is a fibrous inflammatory process related to immunomodulation. The involvement of the pancreato-biliary tract, retroperitoneum/aorta, head and neck, and salivary glands are the most frequently observed disease phenotypes, differing in their epidemiological features, serological findings, and prognostic outcomes. IgG4-RD was combined with oesophageal ulcers, and the patients were infected with cytomegalovirus at the time of the examination. This constituted a huge challenge in the diagnosis and treatment of oesophageal ulcers. We report the case of a 53-year-old male who experienced nausea, vomiting, and anaemia recurrently for many years. According to his medical records, an upper gastrointestinal endoscopy revealed an oesophageal ulcer, and he had had numerous hospital visits for anaemia but with no definitive diagnosis, and he had responded poorly to therapy. However, with persistent symptoms, he came to our hospital and, according to the results of the upper gastrointestinal endoscopy, a serum IgG4 test, and histopathological and immunohistochemical staining, he was finally diagnosed with IgG4-related oesophageal disease combined with a cytomegalovirus infection. We hope that through this case, we can learn more about IgG4-RD and, at the same time, give clinicians a better understanding of IgG4-RD combined with oesophageal ulceration, a new understanding of cytomegalovirus infections, and improved clinical knowledge. Full article

We evaluated the reading characteristics of normal-sighted young adults using C-Read to provide baseline healthy population values. We also investigated the relationship between the National Eye Institute’s Visual Functioning Questionnaire (VFQ-25) score and reading ability, myopia, and hours of screen use, focusing on the extent to which these factors affect participants’ visual function and, ultimately, their vision-related quality of life (QoL). Overall, 207 young, healthy participants (414 eyes) aged 18–35 years were tested for reading speed using C-Read connected to a smartphone-based application between December 2022 and January 2023. Each participant received a VFQ-25 questionnaire to evaluate vision-related QoL. Data on daily e-screen usage hours were collected. Among the participants, 91 (44.0%) were women; their mean (SD) age was 22.45 (4.01) years. The mean (SD) reading acuity (RA) was 0.242 (0.124), 0.249 (0.120), and 0.193 (0.104) logarithmic minimum angle of resolution (logMAR) for the right, left, and both eyes, respectively. The mean (SD) maximum reading speed (MRS) was 171.65 (46.27), 168.59 (45.68), and 185.16 (44.93) words per minute (wpm) with the right, left, and both eyes, respectively. The mean (SD) critical print size (CPS) was 0.412 (0.647), 0.371 (0.229), and 0.419 (1.05) logMAR per the right, left, and both eyes, respectively. The RA and CPS were significantly different between sexes (p = 0.002 and p = 0.001). MRS was significantly different between the education level (p = 0.005) and myopia level groups (p = 0.010); however, it was not clear whether this difference was confounded by age. The myopic power in diopters significantly affected RA (coefficient, −0.012; 95% CI, −0.018 to −0.006; p = 0.001); screen time significantly affected MRS (coefficient, 0.019; 95% CI, 0.57 to 6.33; p = 0.019). RA (coefficient, −21.41; 95% CI, −33.74 to −9.08; p = 0.001) and duration of screen use (coefficient, -0.86; 95% CI, −1.29 to −0.43; p < 0.001) independently had a significantly negative correlation with VFQ-25 scores. Our findings provide a baseline value for C-Read in normal-sighted young adults. Refractive status significantly affected RA, while screen time significantly affected MRS. Interventions aimed at enhancing RA may have the potential to maximize vision-related QoL and enable older adults with impaired vision to achieve greater outcomes. Future, larger-scale, C-Read experiments will help provide newer, more optimal methods for the early diagnosis of visual impairment. Full article

Trastuzumab plus chemotherapy is the standard of care for the first-line treatment of patients with HER2+ advanced esophagogastric (EG) cancer. Nevertheless, patients frequently develop resistance. In preclinical models, we identified the overexpression of Fibroblast Growth Factor Receptor (FGFR) 3 as a mechanism potentially involved in trastuzumab-acquired resistance. FGFR inhibition could be a potential mechanism as a second-line treatment. In this Simon’s two-stage phase 2, single arm study, patients with advanced EG cancer refractory to trastuzumab-containing therapies received pemigatinib, an inhibitor of FGFR. The primary end point was the 12-week progression-free survival rate. Translational analyses were performed on tissue and plasma samples. Eight patients were enrolled in the first stage. Although the 6-week disease control rate was 25%, only one patient achieved a stable disease after 12 weeks of treatment. The trial was discontinued before the second stage. Two out of six evaluable tumor samples expressed FGFR3. No FGFRs amplification was detected. HER2 amplification was lost in three out of eight patients. Three patients had an high Tumor Mutational Burden, and two of them are significantly long-term survivors. These results do not support the therapeutic efficacy of targeting FGFR in unselected patients with advanced EG cancer, who are refractory to trastuzumab-containing therapies. Full article

For sinus grafting, different methods and materials are available. One possible shortcoming of particulate bone grafts is either overfilling or augmenting the planned implant area insufficiently. To overcome this risk and to determine the implant position prior augmentation, we present an approach using three-dimensional printed scaffolds. A patient with a remaining anterior dentition and bilateral severely atrophied posterior maxilla was seeking oral rehabilitation. The cone beam computed tomography (CBCT) showed residual bone heights between one and two millimeters. Following the three-dimensional reconstruction of the CBCT data, the positions of the implants were determined in areas 16 and 26. Three-dimensional scaffolds adapted to the topography of the sinus were virtually designed and printed using a calcium phosphate cement paste. Bilateral sinus floor augmentation applying the printed scaffolds with an interconnecting porosity followed. After nine months, a satisfying integration of the scaffolds was obvious. At the re-entry, vital bone with sufficient blood supply was found. One implant could be placed in positions 16 and 26, respectively. After five months, the implants could be uncovered and were provided with a temporary denture. The application of three-dimensionally printed scaffolds from calcium phosphate cement paste seems to be a promising technique to graft the severely atrophied posterior maxilla for the placement of dental implants. Full article