Graph Convolutional Network with Self-supervised Learning for Brain Disease Classification.

Brain functional network (BFN) analysis has become a popular method for identifying neurological diseases at their early stages and revealing sensitive biomarkers related to these diseases. Due to the fact that BFN is a graph with complex structure, graph convolutional networks (GCNs) can be naturally used in the identification of BFN, and can generally achieve an encouraging performance if given large amounts of training data. In practice, however, it is very difficult to obtain sufficient brain functional data, especially from subjects with brain disorders. As a result, GCNs usually fail to learn a reliable feature representation from limited BFNs, leading to overfitting issues. In this paper, we propose an improved GCN method to classify brain diseases by introducing a self-supervised learning (SSL) module for assisting the graph feature representation. We conduct experiments to classify subjects with mild cognitive impairment (MCI) and autism spectrum disorder (ASD) respectively from normal controls (NCs). Experimental results on two benchmark databases demonstrate that our proposed scheme tends to obtain higher classification accuracy than the baseline methods.

Preliminary study of indocyanine green-guided laparoscopic lateral lymph node dissection for rectal cancer.

BACKGROUND: LLNM can occur in mid-low rectal cancer, but LLND in patients with rectal cancer presents certain challenges. Recent years have seen the progressive application of ICG fluorescence imaging technology in colorectal surgery. This study aimed to explore the effectiveness of ICG-guided laparoscopic LLND for rectal cancer. METHODS: We applied ICG-guided laparoscopic lateral lymph node dissection in 11 patients diagnosed as rectal cancer with lateral lymph node metastasis. RESULTS: All 11 patients in this group successfully completed ICG-guided laparoscopic LLND for rectal cancer with good lateral lymph node imaging. CONCLUSIONS: ICG-guided laparoscopic LLND for rectal cancer is safe and represents a feasible solution, thereby providing valuable guidance for intraoperative lymph node dissection.

MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression. / MiR-4465修饰的间质干细胞来源的小细胞外囊泡通过靶向LOXL2表达抑制肝纤维化的进展.

Liver fibrosis is a significant health burden, marked by the consistent deposition of collagen. Unfortunately, the currently available treatment approaches for this condition are far from optimal. Lysyl oxidase-like protein 2 (LOXL2) secreted by hepatic stellate cells (HSCs) is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been proposed as a potential treatment option for chronic liver disorders. Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues. It is currently unclear whether microRNA-4465 (miR-4465) can target LOXL2 and inhibit HSC activation. Additionally, it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis. This study explored the effect of miR-4465-modified MSC-sEV (MSC-sEVmiR-4465) on LOXL2 expression and liver fibrosis development. The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC. Moreover, MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro. MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model. MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells. In conclusion, we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2, which might provide a promising therapeutic strategy for liver diseases.

Nonvolatile Modulation of Bi2O2Se/Pb(Zr,Ti)O3 Heteroepitaxy.

The pursuit of high-performance electronic devices has driven the research focus toward 2D semiconductors with high electron mobility and suitable band gaps. Previous studies have demonstrated that quasi-2D Bi2O2Se (BOSe) has remarkable physical properties and is a promising candidate for further exploration. Building upon this foundation, the present work introduces a novel concept for achieving nonvolatile and reversible control of BOSe's electronic properties. The approach involves the epitaxial integration of a ferroelectric PbZr0.2Ti0.8O3 (PZT) layer to modify BOSe's band alignment. Within the BOSe/PZT heteroepitaxy, through two opposite ferroelectric polarization states of the PZT layer, we can tune the Fermi level in the BOSe layer. Consequently, this controlled modulation of the electronic structure provides a pathway to manipulate the electrical properties of the BOSe layer and the corresponding devices.

Assessment of cardiac adverse events following COVID-19 vaccination by speckle tracking echocardiography.

Cardiac discomfort has been reported periodically in COVID-19-vaccinated individuals. Thus, this study aimed to evaluate the role of myocardial strains in the early assessment of the clinical presentations after COVID-19 vaccination. Totally, 121 subjects who received at least one dose of vaccine within 6 weeks underwent laboratory tests, electrocardiogram (ECG), and echocardiogram. Two-dimensional speckle tracking echocardiography (2D-STE) was implemented to analyze changes in the left ventricular myocardium. After vaccination, 66 individuals (55.4 ± 17.4 years) developed cardiac discomforts, such as chest tightness, palpitations, dyspnea, and chest pain. The ECG readings exhibited both premature ventricular contractions and premature atrial contractions (n = 24, 36.4%), while none of the individuals in the control group manifested signs of cardiac arrhythmia. All had normal serum levels of creatine phosphokinase, creatine kinase myocardial band, troponin, N-terminal pro b-type natriuretic peptide, platelets, and D-dimer. Left ventricular ejection fraction in the symptomatic group (71.41% ± 7.12%) and the control group (72.18% ± 5.11%) (p = 0.492) were normal. Use of 2D-STE presented global longitudinal strain (GLS) and global circumferential strain (GCS) was reduced in the symptomatic group (17.86% ± 3.22% and 18.37% ± 5.22%) compared to the control group (19.54% ± 2.18% and 20.73% ± 4.09%) (p = 0.001 and p = 0.028). COVID-19 vaccine-related cardiac adverse effects can be assessed early by 2D-STE. The prognostic implications of GLS and GCS enable the evaluation of subtle changes in myocardial function after vaccination.

MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression. / MiR-4465修饰的间质干细胞来源的小细胞外囊泡通过靶向LOXL2表达抑制肝纤维化的进展.

Liver fibrosis is a significant health burden, marked by the consistent deposition of collagen. Unfortunately, the currently available treatment approaches for this condition are far from optimal. Lysyl oxidase-like protein 2 (LOXL2) secreted by hepatic stellate cells (HSCs) is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been proposed as a potential treatment option for chronic liver disorders. Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues. It is currently unclear whether microRNA-4465 (miR-4465) can target LOXL2 and inhibit HSC activation. Additionally, it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis. This study explored the effect of miR-4465-modified MSC-sEV (MSC-sEVmiR-4465) on LOXL2 expression and liver fibrosis development. The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC. Moreover, MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro. MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model. MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells. In conclusion, we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2, which might provide a promising therapeutic strategy for liver diseases.

An improved attention module based on nnU-Net for segmenting primary central nervous system lymphoma (PCNSL) in MRI images1.

BACKGROUND: Accurate volumetric segmentation of primary central nervous system lymphoma (PCNSL) is essential for assessing and monitoring the tumor before radiotherapy and the treatment planning. The tedious manual segmentation leads to interindividual and intraindividual differences, while existing automatic segmentation methods cause under-segmentation of PCNSL due to the complex and multifaceted nature of the tumor. OBJECTIVE: To address the challenges of small size, diffused distribution, poor inter-layer continuity on the same axis, and tendency for over-segmentation in brain MRI PCNSL segmentation, we propose an improved attention module based on nnUNet for automated segmentation. METHODS: We collected 114 T1 MRI images of patients in the Huashan Hospital, Shanghai. Then randomly split the total of 114 cases into 5 distinct training and test sets for a 5-fold cross-validation. To efficiently and accurately delineate the PCNSL, we proposed an improved attention module based on nnU-Net with 3D convolutions, batch normalization, and residual attention (res-attention) to learn the tumor region information. Additionally, multi-scale dilated convolution kernels with different dilation rates were integrated to broaden the receptive field. We further used attentional feature fusion with 3D convolutions (AFF3D) to fuse the feature maps generated by multi-scale dilated convolution kernels to reduce under-segmentation. RESULTS: Compared to existing methods, our attention module improves the ability to distinguish diffuse and edge enhanced types of tumors; and the broadened receptive field captures tumor features of various scales and shapes more effectively, achieving a 0.9349 Dice Similarity Coefficient (DSC). CONCLUSIONS: Quantitative results demonstrate the effectiveness of the proposed method in segmenting the PCNSL. To our knowledge, this is the first study to introduce attention modules into deep learning for segmenting PCNSL based on brain magnetic resonance imaging (MRI), promoting the localization of PCNSL before radiotherapy.

Comparison of the efficacy, safety and postoperative quality of life between modified side overlap anastomosis and double-tract anastomosis after laparoscopic proximal gastrectomy.

PURPOSE: To compare the surgical safety and postoperative quality of life (QOL) between side overlap anastomosis (SOA) and double-tract anastomosis (DTA) after laparoscopic proximal gastrectomy (LPG). METHODS: This retrospective cohort study included 43 patients with proximal gastric cancer (PGC) who underwent LPG and were admitted to the Second Affiliated Hospital of Fujian Medical University between August 2020 and December 2022 were in. Their clinical and follow-up data were collected. The patients were divided into the modified SOA (mSOA) (n = 20) and DTA (n = 23) groups based on the anastomosis methods used. The main outcome measures included the QOL of patients 1 year after surgery, and the evaluation criteria were based on the postgastrectomy syndrome assessment scale. Secondary outcome measures included intraoperative and postoperative conditions, postoperative long-term complications and nutritional status 3, 6 and 12 months after surgery. RESULTS: No significant differences were observed in intraoperative and postoperative conditions (P > 0.05) between the mSOA and DTA groups. The mSOA group showed a decreased incidence of reflux esophagitis 1 year after surgery compared with the DTA group (P < 0.05), and no statistically significant differences were noticed between the two groups in terms of other postoperative complications (P > 0.05). The mSOA group showed better QOL when compared with the DTA group (P < 0.05). No significant differences were recorded in postoperative nutritional status between the two groups (P > 0.05). CONCLUSION: The efficacy and safety of LPG with mSOA for PGC were comparable. When compared with the DTA group, the mSOA group seems to show reduced incidence of gastroesophageal reflux and improved QOL, which makes mSOA one of the ideal surgical methods for PGC.

Circ_0044235 regulates the development of osteoarthritis by the modulation of miR-375/PIK3R3 axis.

BACKGROUND: Circular RNAs (circRNAs) play an important role in osteoarthritis (OA). However, the role of circRNA in OA is still unclear. Here, we explored the role and mechanism of circ_0044235 in OA. METHODS: CHON-001 cells were treated with IL-1ß to establish OA model in vitro. The levels of circ_0044235, miR-375 and phosphoinositide 3-kinase (PI3K) regulatory subunit 3 (PIK3R3) were detected by quantitative real-time PCR. Cell count kit-8 assay and flow cytometry assay were used to detect cell viability and apoptosis. The concentrations of inflammation factors were determined by enzyme-linked immunosorbent assay. Western blot was used to detect protein levels. The interaction between miR-375 and circ_0044235 or PIK3R3 was analyzed by dual-luciferase reporter assay and RNA immunoprecipitation assay. RESULTS: Circ_0044235 was significantly decreased in OA cartilage tissue and IL-1ß-treated CHON-001 cells. Overexpression of circ_0044235 promoted IL-1ß-stimulated CHON-001 cell viability and inhibited apoptosis, inflammation, and extracellular matrix (ECM) degradation. In mechanism analysis, circ_0044235 could act as a sponge for miR-375 and positively regulate PIK3R3 expression. In addition, miR-375 ameliorated the effect of circ_0044235 overexpression on IL-1ß-mediated CHON-001 cells injury. In addition, miR-375 inhibition mitigated IL-1ß-induced CHON-001 cell injury, while PIK3R3 silencing restored the effect. CONCLUSION: Circ_0044235 knockdown alleviated IL-1ß-induced chondrocytes injury by regulating miR-375/PIK3R3 axis, confirming that circ_0044235 might be a potential target for OA treatment.

Clinical efficacy of modified Kamikawa anastomosis in patients with laparoscopic proximal gastrectomy.

BACKGROUND: With the increasing incidence of proximal gastric cancer, laparoscopic proximal gastrectomy has been applied. However, reflux esophagitis often occurs after traditional esophagogastric anastomosis. In order to solve this problem, several methods of digestive tract reconstruction have emerged, but the most satisfying method remains to be discussed. Therefore, we modified traditional Kamikawa anastomosis to investigate the appropriate digestive tract reconstruction in laparoscopic proximal gastrectomy. AIM: To discuss the clinical efficacy of modified Kamikawa anastomosis in laparoscopic proximal gastrectomy. METHODS: A retrospective case series was adopted. Clinicopathological data were collected from 26 patients who underwent laparoscopic proximal gastrectomy and modified Kamikawa anastomosis at our hospital from January 2020 to September 2022. The operation conditions, postoperative recovery, postoperative complications, and follow-up data were collected and analyzed. RESULTS: All the patients were successfully operated on without conversion to laparotomy. The duration of operation and digestive tract reconstruction were 203.500 (150-224) min and 87.500 (73-111) min, respectively. The intraoperative amount of bleeding was 20.500 mL ± 0.696 mL. The time of postoperative first flatus, the first postoperative fluid intake, and the postoperative length of stay were 2 (1-3) d, 4 (3-5) d, and 9 (8-10) d, respectively. All the patients were followed up for 12-23 months. The body mass index at 6 and 12 months after surgery were 22.577 kg/m2 ± 3.098 kg/m2 and 22.594 kg/m2 ± 3.207 kg/m2, respectively. The nutrition risk screening 2002 score, the patient-generated subjective global assessment score, and the gastroesophageal reflux disease scale score were good at 6 and 12 months after surgery. Reflux esophagitis and anastomotic stenosis were not observed in any of the patients during their 12-month postoperative gastroscopy or upper gastrointestinal tract visits. All the patients exhibited no tumor recurrence or metastasis. CONCLUSION: The modified Kamikawa anastomosis is safe and feasible for laparoscopic proximal gastrectomy and has good antireflux effects and nutritional status.

Critical review on the research of chemical structure, bioactivities, and mechanism of actions of Dendrobium officinale polysaccharide.

Dendrobium officinale (Tie-Pi-Shi-Hu) is a precious traditional Chinese medicine (TCM). The principal active components are polysaccharides (DOP), which have a high potency in therapeutic applications. However, limitations in structure analysis and underlying mechanism investigation impede its further research. This review systemically and critically summarises current understanding in both areas, and points out the influence of starch impurities and the role of gut microbiota in DOP research. As challenges faced in studying natural polysaccharide investigations are common, this review contributes to a broader understanding of polysaccharides beyond DOP.

Efficacy and safety of camrelizumab combined with oxaliplatin and S-1 as neoadjuvant treatment in locally advanced gastric or gastroesophageal junction cancer: A phase II, single-arm study.

PURPOSE: In the present study, we aimed to evaluate the efficacy and safety of camrelizumab combined with oxaliplatin plus S-1 in patients with resectable gastric or gastroesophageal junction cancer. METHODS: In this single-arm, phase II clinical trial, patients with locally advanced gastric or gastroesophageal junction adenocarcinoma were enrolled to receive three cycles of neoadjuvant camrelizumab and oxaliplatin plus S-1 every 3 weeks, followed by surgical resection and adjuvant therapy with the same regimen. The primary endpoint was pathological complete response (pCR) (ypT0) rate and secondary endpoints were R0 resection rate, total pCR (tpCR, ypT0N0) rate, major pathological response (MPR) rate, downstaging, objective response rate (ORR), disease control rate (DCR), event-free survival (EFS), overall survival (OS), and safety. RESULTS: Between September, 2020 and January, 2022, a total of 29 patients were enrolled in the present study, all of whom completed neoadjuvant therapy and underwent surgery. Three (10.3%) (95% CI: 2.2-27.4) patients achieved pCR as well as tpCR, 20 (69.0%) patients had MPR and 28 (96.6%) patients achieved R0 resection. Treatment-emergent adverse events (AEs) of any grade were observed in 24 (82.8%) patients. Immune-related adverse events of any grade were reported in 13 (44.8%) patients, whereas no grade 3 or higher adverse events occurred. CONCLUSION: The neoadjuvant therapy with camrelizumab in combination with oxaliplatin and S-1 showed a modest pCR rate, and favorable MPR rate and safety profile in patients with gastric or gastroesophageal junction cancer.

Long-term outcomes of inferomedial orbital wall decompression in Graves' ophthalmopathy in an Asian population: A 30-year retrospective study.

PURPOSE: This study aims to evaluate the long-term outcomes of inferomedial orbital wall decompression (IMOD) in Graves' ophthalmopathy (GO). METHODS: A retrospective review of 422 eyes of 226 patients with GO-related cosmetically disfiguring proptosis (COS), dysthyroid optic neuropathy (DON), or exposure keratopathy (EXP) who received IMOD from 1989 to 2020 was conducted. Hertel value (HE) and corrected visual acuity (CVA) were evaluated at baseline and regularly thereafter. Proptosis recurrence, diplopia, and adjuvant surgeries were assessed. Complete success was defined as proptosis reduction over 2 mm without recurrence and improved diplopia. Partial success was defined as proptosis reduction without recurrence but with persistent or new-onset diplopia, and failure as proptosis recurrence. RESULTS: After follow-up for 40.1 ± 39.6 months (range, 6-239 months), 236 eyes (55.9%) achieved complete success, 175 eyes (41.5%) achieved partial success, and 11 eyes (2.6%) had failure. Significant CVA improvement was observed in both DON and COS groups (P < 0.001 and P = 0.045, respectively). Average proptosis reduction was 5.2 ± 2.2 mm, with a significant increase of 0.5 mm after long-term follow-up (P < 0.001). Incidence of proptosis recurrence was 2.6%. Surgical success rate of COS group was positively correlated with preoperative HE. CONCLUSION: IMOD demonstrated excellent success rate in all three subgroups with a low proptosis recurrence rate and improved visual outcome in both DON and COS groups. Delayed proptosis reduction effect of IMOD may result in delayed-onset asymmetry, especially in the unilateral group.

pH Mapping of Gliomas Using Quantitative Chemical Exchange Saturation Transfer MRI: Quasi-Steady-State, Spillover-, and MT-Corrected Omega Plot Analysis.

BACKGROUND: Quantitative in-situ pH mapping of gliomas is important for therapeutic interventions, given its significant association with tumor progression, invasion, and metastasis. Although chemical exchange saturation transfer (CEST) offers a noninvasive way for pH imaging based on the pH-dependent exchange rate (ksw ), the reliable quantification of ksw in glioma remains constrained due to technical challenges. PURPOSE: To quantify the pH of gliomas by measuring the proton exchange rate through optimized omega plot analysis. STUDY TYPE: Prospective. PHANTOMS/ANIMAL MODEL/SUBJECTS: Creatine and murine brain lysates phantoms, six rats with glioma xenograft model, and three patients with World Health Organization grade 2-4 gliomas. FIELD STRENGTH/SEQUENCE: 11.7 T, 7.0 T, CEST imaging, T2 -weighted (T2 W) imaging, and T1 -mapping. ASSESSMENT: Omega plot analysis, quasi-steady-state (QUASS) analysis, multi-pool Lorentzian fitting, amine and amide concentration-independent detection, pH enhanced method with the combination of amide and guanidyl (pHenh ), and magnetization transfer ratio (MTR) were utilized for pH metric quantification. The clinical outcomes were determined through radiologic follow-up and histopathological analysis. STATISTICAL TESTS: Mann-Whitney U test was performed to compare glioma with normal tissue, and Pearson's correlation analysis was used to assess the relationship between ksw and other parameters. RESULTS: In vitro experiments reveal that the determined ksw at 2 ppm increases exponentially with pH (creatine phantoms: ksw = 106 + 0.147 × 10(pH-4.198) ; lysates: ksw = 185.1 + 0.101 × 10(pH-3.914) ). Omega plot analysis exhibits a linear correlation between 1/MTRRex and 1/ω1 2 in the glioma xenografts (R2 > 0.98) and glioma patients (R2 > 0.99). The exchange rate in the rat glioma decreases compared to the contralateral normal tissue (349.46 ± 30.40 s-1 vs. 403.54 ± 51.01 s-1 , P = 0.025), while keeping independence from changes in concentration (r = 0.5037, P = 0.095). Similar pattern was observed in human data. DATA CONCLUSION: Utilizing QUASS-based, spillover-, and MT-corrected omega plot analysis for the measurement of exchange rates, offers a feasible method for quantifying pH within glioma. LEVEL OF EVIDENCE: NA TECHNICAL EFFICACY: Stage 1.

Better survival was found in patients treated with breast-conserving surgery compared with mastectomy in malignant phyllodes tumor of the breast.

Malignant phyllodes tumor of the breast (MPTB) is a rare type of breast cancer. The prognosis between breast-conserving surgery (BCS) and mastectomy remains unclear in MPTB. Therefore, long-term survival was investigated between BCS and mastectomy in MPTB via the Surveillance, Epidemiology, and End Results (SEER) database. MPTB patients with T1-2/N0 stage between 2000 and 2015 from SEER database were retrospectively reviewed. Prognosis between different surgical approaches was assessed by Kaplan-Meier curves and Cox proportional hazards analysis. A total of 795 patients were enrolled with a median follow-up of 126 months. BCS was associated with significantly increased 10-year overall survival (OS) (89.2% vs. 81.1%, p = 0.002) and breast cancer-specific survival (BCSS) (95.2% vs. 90%, p = 0.004) compared with mastectomy. Multivariate analysis showed better OS (HR = 0.587, 95% CI 0.406-0.850, p = 0.005) and BCSS (HR = 0.463, 95%CI 0.267-0.804, p = 0.006) in the BCS group than the mastectomy group. After 1:1 propensity score matching (PSM), improved 10-year OS (89.2% vs.81%, p = 0.023) and BCSS (95.8% vs. 90.1%, p = 0.033) were observed in BCS compared with mastectomy. This study found the survival benefit of BCS over mastectomy in patients with early-stage MPTB. BCS should be recommended as a priority in MPTB patients when both surgical approaches are feasible.

Selectively Probing the Magnetic Resonance Signals of γ-Aminobutyric Acid in Human Brains In Vivo.

BACKGROUND: Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in human brains, playing a role in the pathogenesis of various psychiatric disorders. Current methods have some non-neglectable shortcomings and noninvasive and accurate detection of GABA in human brains is long-term challenge. PURPOSE: To develop a pulse sequence capable of selectively detecting and quantifying the 1 H signal of GABA in human brains based on optimal controlled spin singlet order. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: A phantom of GABA (pH = 7.3 ± 0.1) and 11 healthy subjects (5 females and 6 males, body mass index: 21 ± 3 kg/m2 , age: 25 ± 4 years). FIELD STRENGTH/SEQUENCE: 7 Tesla, 3 Tesla, GABA-targeted magnetic resonance spectroscopy (GABA-MRS-7 T, GABA-MRS-3 T), magnetization prepared two rapid acquisition gradient echoes sequence. ASSESSMENT: By using the developed pulse sequences applied on the phantom and healthy subjects, the signals of GABA were successfully selectively probed. Quantification of the signals yields the concentration of GABA in the dorsal anterior cingulate cortex (dACC) in human brains. STATISTICAL TESTS: Frequency. RESULTS: The 1 H signals of GABA in the phantom and in the human brains of healthy subjects were successfully detected. The concentration of GABA in the dACC of human brains was 3.3 ± 1.5 mM. DATA CONCLUSION: The developed pulse sequences can be used to selectively probe the 1 H MR signals of GABA in human brains in vivo. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 1.

FGFR1/2/3-rearranged carcinoma of the head and neck: expanded histological spectrum crossing path with high-risk HPV in the sinonasal tract.

AIMS: Oncogenic FGFR1/2/3 rearrangements are found in various cancers. Reported cases in head and neck (HN) are mainly squamous cell carcinomas (SCCs) with FGFR3::TACC3 fusions, a subset of which also harbour high-risk human papillomavirus (HPV). However, the knowledge of the clinicopathological spectrum of FGFR-rearranged head and neck carcinomas (FHNC) is limited. METHODS AND RESULTS: A retrospective MSK-fusion clinical sequencing cohort 2016-23 was searched to identify malignant tumours in the HN region harbouring FGFR1/2/3 fusion. FHNC were characterised by histological examination, immunohistochemistry and molecular analysis. Electronic medical records were reviewed. Three FHNC were identified. Two cases (cases 1 and 2) involved sinonasal tract and were high-grade carcinomas with squamous, basaloid, glandular and/or ductal-myoepithelial features. Case 1 arose in a 79-year-old man and harboured FGFR2::KIF1A fusion. Case 2 arose in a 58-year-old man, appeared as HPV-related multiphenotypic sinonasal carcinoma (HMSC), and was positive for FGFR2::TACC2 fusion and concurrent high-risk HPV, non-type 16/18. Case 3 was FGFR3::TACC3 fusion-positive keratinising SCCs arising in the parotid of a 60-year-old man. All three cases presented at stage T4. Clinical follow-up was available in two cases; case 1 remained disease-free for 41 months post-treatment and case 3 died of disease 2 months after the diagnosis. CONCLUSIONS: FHNC include a morphological spectrum of carcinomas with squamous features and may occur in different HN locations, such as parotid gland and the sinonasal tract. Sinonasal cases can harbour FGFR2 rearrangement with or without associated high-risk HPV. Timely recognition of FHNC could help select patients potentially amenable to targeted therapy with FGFR inhibitors. Further studies are needed (1) to determine if FGFR2 rearranged/HPV-positive sinonasal carcinomas are biologically distinct from HMSC, and (2) to elucidate the biological and clinical significance of FGFR2 rearrangement in the context of high-risk HPV.