Molecular serotyping of diarrheagenic Escherichia coli with a MeltArray assay reveals distinct correlation between serotype and pathotype.

Diarrheagenic Escherichia coli serotypes are associated with various clinical syndromes, yet the precise correlation between serotype and pathotype remains unclear. A major barrier to such studies is the reliance on antisera-based serotyping, which is culture-dependent, low-throughput, and cost-ineffective. We have established a highly multiplex PCR-based serotyping assay, termed the MeltArray E. coli serotyping (EST) assay, capable of identifying 163 O-antigen-encoding genes and 53 H-antigen-encoding genes of E. coli. The assay successfully identified serotypes directly from both simulated and real fecal samples, as demonstrated through spike-in validation experiments and a retrospective study. In a multi-province study involving 637 E. coli strains, it revealed that the five major diarrheagenic pathotypes have distinct serotype compositions. Notably, it differentiated 257 Shigella isolates into four major Shigella species, distinguishing them from enteroinvasive E. coli based on their distinct serotype profiles. The assay's universality was further corroborated by in silico analysis of whole-genome sequences from the EnteroBase. We conclude that the MeltArray EST assay represents a paradigm-shifting tool for molecular serotyping of E. coli, with potential routine applications for comprehensive serotype analysis, disease diagnosis, and outbreak detection.

Association of child maltreatment and school bullying among Chinese adolescents: the mediating role of peer relationships.

BACKGROUND: School bullying, a serious problem for the physical and mental health of adolescents, is presently a significant issue in China. It is essential to recognize and comprehend potential risk factors and establish efficient preventive strategies. The purpose of this study was to examine the association between childhood maltreatment and school bullying in adolescents and to assess the mediating role of peer relationships. METHODS: Between March and April 2024, a cross-sectional survey was conducted among 2119 adolescents aged between 12 and 18 years in Guangdong Province, China. Self-report questionnaires were employed to collect data on childhood maltreatment, school bullying, and peer relationships. Subgroup analyses and mediating effects modeling were employed to analyze the data. RESULTS: The results indicated that adolescents who had experienced maltreatment were more at risk of bullying victimization (OR: 2.92, 95% CI: 2.34-3.64, P < 0.001), bullying perpetration (OR: 2.84, 95% CI: 1.99-4.05, P < 0.001), and bully-victimization (OR: 2.93, 95% CI: 1.95-4.41, P < 0.001), compared to adolescents who have not. Sexual abuse showed the most significant connection with all forms of bullying. The mediating effect of peer relationships was found to mediate the association between child maltreatment and bullying behaviour. The results indicated that worse peer relationships may exacerbate the adverse effects of maltreatment experiences and increase the risk of adolescents becoming bullies, either perpetrators or victims of bullying. CONCLUSIONS: Child maltreatment has been identified as one of the most significant influences on bullying behaviour in adolescents. The quality of peer relationships has been demonstrated to play an important role in preventing and reducing the occurrence of bullying. The results underscore the crucial role of early intervention in cases of child maltreatment and the fostering of positive peer relationships in schools.

Arctigenin Modulates Adipogenic-Osteogenic Balance in the Bone Marrow Microenvironment of Ovariectomized Rats via the MEK1/PPARγ/Wnt/ß-Catenin Pathway.

Arctigenin (Ar) is a promising therapeutic candidate for postmenopausal osteoporosis (PMOP). This study explores its mechanism by examining its effects on adipogenesis and osteogenesis in ovariectomized (OVX) rats. In vitro, Ar effectively suppressed the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) from OVX rats, reducing lipid droplet formation and downregulating proteins associated with lipid synthesis. In vivo, Ar treatment significantly reduced bone loss, inhibited adipocyte development, improved lipid metabolism, and promoted bone formation in OVX rats. Mechanistically, Ar inhibited the phosphorylation of Mitogen-Activated Protein Kinase 1 (MEK1), downregulated Peroxisome Proliferator-Activated Receptor gamma (PPARγ), promoted the accumulation of ß-catenin in the nucleus, and prevented the direct binding of PPARγ to ß-catenin in BMSCs. This regulation of the PPARγ/Wnt signaling axis underlies its dual role in inhibiting adipogenesis and promoting osteogenesis. Notably, co-treatment with rosiglitazone (RGZ) reversed the effects of Ar on adipogenesis and osteogenesis without affecting MEK1 inhibition. These findings offer valuable insights into arctigenin's potential as a therapeutic strategy for PMOP by modulating MEK1 signaling and regulating the PPARγ/Wnt axis.

TCF3 as a multidimensional biomarker: oncogenicity, genomic alterations, and immune landscape in pan-cancer analysis.

Transcription factor 3 (TCF3), a pivotal member of the TCF/LEF family, plays a critical role in tumorigenesis. Nonetheless, its impact on the tumor microenvironment (TME) and cancer phenotypes remains elusive. We perform an exhaustive analysis of TCF3 expression, DNA variation profiles, prognostic implications, and associations with the TME and immunological aspects. This study is based on a large-scale pan-cancer cohort, encompassing over 17,000 cancer patients from multiple independent datasets, validated by in vitro assays. Our results show that TCF3/4/7 exhibits differential expression patterns between normal and tumor tissues across pan-cancer analyses. Mutational analysis of TCF3 across diverse cancer types reveals the highest alteration rates in biliary tract cancer. Additionally, mutations and single nucleotide variants in TCF3/4/7 are found to exert varied effects on patient prognosis. Importantly, TCF3 emerges as a robust predictor of survival across all cancer cohorts and among patients receiving immune checkpoint inhibitors. Elevated TCF3 expression is correlated with more aggressive cancer subtypes, as validated by immunohistochemistry and diverse cohort data. Furthermore, TCF3 expression is positively correlated with intratumoral heterogeneity and angiogenesis. In vitro investigations demonstrate that TCF3 is involved in epithelial-mesenchymal transition, migration, invasion, and angiogenesis. These effects are likely mediated through the interaction of TCF3 with the NF-κB/MMP2 pathway, which is modulated by IL-17A in human uveal melanoma MUM2B cells. This study elucidates, for the first time, the significant associations of TCF3 with DNA variation profiles, prognostic outcomes, and the TME in multiple cancer contexts. TCF3 holds promise as a molecular marker for diagnosis and as a potential target for novel therapeutic strategies, particularly in uveal melanoma.

Predicting tremor improvement after MRgFUS thalamotomy in essential tremor from preoperative spontaneous brain activity: A machine learning approach.

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) thalamotomy is an emerging technique for medication-refractory essential tremor (ET), but with variable outcomes. This study used pattern regression analysis to identify brain signatures predictive of tremor improvements. Fifty-four ET patients (mean age = 63.06 years, standard deviation (SD) = 10.55 years, 38 males) underwent unilateral MRgFUS thalamotomy and were scanned for resting-state functional magnetic resonance imaging (rs-fMRI). Seventy-four healthy controls (mean age = 58.09 years, SD = 10.30 years, 38 males) were recruited for comparison. Tremor responses at 12 months posttreatment were evaluated by the Clinical Rating Scale for Tremor. The fractional amplitude of low-frequency fluctuations (fALFF) was calculated from rs-fMRI data. Two-sample t-test was used to generate a disease-specific mask, within which Multivariate Kernel Ridge Regression analyses were conducted. Predicted and actual clinical scores were compared using Pearson's correlation coefficient (r) and normalized mean squared error (Norm. MSE). Permutation test and leave-one-out strategy were applied for results validation. KRR identified fALFF patterns that significantly predicted the hand tremor improvement (r = 0.23, P = 0.025; Norm. MSE = 0.05, P = 0.026) and the postural tremor improvement (r = 0.28, P = 0.025; Norm. MSE = 0.06, P = 0.023), but not action tremor improvement. Lobule VI of right cerebellum (Cerebelum_6_R), right superior occipital gyrus (Occipital_Sup_R) and lobule X of vermis (Vermis_10) contributed most for hand tremor prediction (normalized weights (NW): 2.77%, 2.40%, 2.34%) while Vermis_10, left supplementary motor area (Supp_Motor_Area_L) and right hippocampus (Hippocampus_R) for postural tremor prediction (NW: 2.69%, 2.12%, 2.05%). The low contributing NW of the individual brain regions suggested that the fALFF pattern as a whole is an overall predicting feature. Preoperative fALFF pattern predicts tremor benefits induced by MRgFUS thalamotomy. ClinicalTrials.gov number: NCT04570046.

Redox-Neutral Coupling of Allyl Alcohols with Trifluoromethyl Ketones via Synergistic Ni-Ti Bimetallic Catalysis.

A redox-neutral coupling of allyl alcohols with trifluoromethyl ketones has been developed via Ni-Ti bimetallic catalysis. This innovative method allows for the efficient synthesis of various ß-tertiary trifluoromethyl alcohol-substituted ketones with yields of up to 98%. The reaction is scalable and compatible with a wide range of substrates, including complex bioactive molecules. Mechanistic studies suggest that the rate-determining step involving ß-H elimination and the presence of the Ti-based Lewis acid, as well as a hydroxyl group on the substrates, is crucial for driving the reactivity of this transformation.

Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1α/VEGF-A/VEGFR2 Signaling Pathway and Inhibiting Inflammation.

Purpose: Neovascular age-related macular degeneration (nAMD) is a prevalent cause of blindness in the elderly. Standard treatment includes anti-vascular endothelial growth factor (anti-VEGF) drugs, such as aflibercept. However, anti-VEGF drugs may have limited efficacy and cause drug resistance. This study explores whether Kavain, an anti-inflammatory molecule from Piper methysticum, can treat choroidal neovascularization (CNV). Methods: Various experiments were conducted to assess the Kavain's toxicity. The impact of Kavain on in vitro cultured endothelial cells was examined through 5-ethynyl-20-deoxyuridine (EdU) assays, transwell migration assays, and tube formation assays. The therapeutic effects of Kavain on CNV were investigated using a laser-induced CNV mice model. To elucidate the mechanism of Kavain, network pharmacology analysis, molecular docking, and western blots were performed. Results: Kavain exhibited no apparent toxicity both in vitro and in vivo. Kavain significantly decreased endothelial cell viability, proliferation, migration, and tube formation ability in a dose-dependent manner compared to the hypoxia groups (P<0.05). Kavain alleviated CNV in the laser-induced CNV mouse model compared to the control groups (P<0.05). These effects were statistically significantly enhanced in the Kavain plus aflibercept groups (P<0.05). Following Kavain administration, the expression levels of various inflammatory factors were markedly reduced in retinal pigment epithelium (RPE)/choroid complexes (P<0.05). Mechanistically, Kavain decreased the activity of the hypoxia-inducible factor 1α (HIF-1α)/VEGF-A/ VEGF receptor 2 (VEGFR2) signaling pathway. Conclusion: Our study is the first to demonstrate Kavain's potential as a promising treatment for nAMD, owing to its dual effects of anti-inflammation and anti-angiogenesis.

High Tibial Osteotomy With Medial Meniscal Posterior Root Tear Reconstruction Yields Improved Radiographic and Functional Outcomes and Healing Rates Compared With Osteotomy Alone.

PURPOSE: To compare preoperative and postoperative clinical and radiologic outcomes between patients undergoing high tibial osteotomy (HTO) with medial meniscal posterior root tear (MMPRT) reconstruction using gracilis tendon graft and those undergoing HTO without MMPRT reconstruction. METHODS: Patients with MMPRTs who underwent HTO between January 2018 and December 2021 with minimum 2-year follow-up were included. All patients were divided into 2 groups based on whether they underwent meniscal root reconstruction with tendon graft: HTO alone (33 cases) and HTO with MMPRT reconstruction (21 cases). Clinical evaluation included the Lysholm score, International Knee Documentation Committee (IKDC) score, and visual analog scale (VAS) score. Functional recovery and radiologic outcomes of the knees were evaluated at the latest follow-up. Meniscal root healing rates and medial meniscal extrusion according to a second magnetic resonance imaging reading were compared between the 2 groups at the latest follow-up. RESULTS: The results showed statistically significant improvements in the postoperative Lysholm score, IKDC score, and VAS score in both groups at the latest follow-up (P < .001). Analysis of the minimal clinically important difference for postoperative outcomes revealed that the percentage of patients who reached the minimal clinically important difference threshold was 100% for the Lysholm score, 100% for the IKDC score, and 100% for the VAS score in the HTO-MMPRT reconstruction group. In comparison, the percentages were 87.9% for the Lysholm score, 90.9% for the IKDC score, and 100% for the VAS score in the HTO-alone group. Additionally, compared with the HTO-alone group, the HTO-MMPRT reconstruction group using gracilis tendon graft showed significantly improved meniscal root healing rates (complete healing, 85.7% vs 45.4% [95% confidence interval, 0.003-0.007]; P = .001) and functional recovery (P < .005) at the final follow-up. Additionally, the HTO-MMPRT reconstruction group showed significantly more improvement in the Kellgren-Lawrence grade (10 of 21 knees vs 6 of 33 knees with improved Kellgren-Lawrence grade, P = .033) and medial meniscal extrusion (2.1 ± 1.0 mm vs 3.1 ± 1.6 mm [95% confidence interval, 0.3-1.7 mm]; P = .007) compared with the HTO-alone group. CONCLUSIONS: HTO with reconstruction of the meniscal root using a tendon graft resulted in improved radiographic and patient-reported outcomes, as well as improved healing rates, compared with HTO alone. LEVEL OF EVIDENCE: Level III, retrospective case-series comparison.

Biodiversity, Distribution and Functional Differences of Fungi in Four Species of Corals from the South China Sea, Elucidated by High-Throughput Sequencing Technology.

Recent studies have predominantly spotlighted bacterial diversity within coral microbiomes, leaving coral-associated fungi in the shadows of scientific inquiry. This study endeavors to fill this knowledge gap by delving into the biodiversity, distribution and functional differences of fungi associated with soft corals Cladiella krempfi and Sarcophyton tortuosum, gorgonian coral Dichotella gemmacea and stony coral Favia speciosa from the South China Sea. Leveraging high-throughput sequencing of fungal internal transcribed spacer-1 (ITS1) region of the rRNA gene, a total of 431 fungal amplicon sequence variants (ASVs) were identified in this study, which indicated that a large number of fungal communities were harbored in the South China Sea corals. Noteworthy among our findings is that 10 fungal genera are reported for the first time in corals, with Candolleomyces, Exophiala, Fomitopsis, Inaequalispora, Kneiffiella, Paraphaeosphaeria, and Yamadazyma belonging to the Ascomycota, and Cystobasidium, Psathyrella, and Solicoccozyma to the Basidiomycota. Moreover, significant differences (p < 0.05) of fungal communities were observed among the various coral species. In particular, the gorgonian coral D. gemmacea emerged as a veritable haven for fungal diversity, boasting 307 unique ASVs. Contrastingly, soft corals S. tortuosum and C. krempfi exhibited modest fungal diversity, with 36 and 21 unique ASVs, respectively, while the stony coral F. speciosa hosted a comparatively sparse fungal community, with merely 10 unique ASVs in total. These findings not only provide basic data on fungal diversity and function in the South China Sea corals, but also underscore the imperative of nuanced conservation and management strategies for coral reef ecosystems worldwide.

Mechanistic insights into zinc oxide nanoparticles induced embryotoxicity via H3K9me3 modulation.

The widespread application of nanoparticles (NPs) in various fields has raised health concerns, especially in reproductive health. Our research has shown zinc oxide nanoparticles (ZnONPs) exhibit the most significant toxicity to pre-implantation embryos in mice compared to other common NPs. In patients undergoing assisted reproduction technology (ART), a significant negative correlation was observed between Zn concentration and clinical outcomes. Therefore, this study explores the impact of ZnONPs exposure on pre-implantation embryonic development and its underlying mechanisms. We revealed that both in vivo and in vitro exposure to ZnONPs impairs pre-implantation embryonic development. Moreover, ZnONPs were found to reduce the pluripotency of mouse embryonic stem cells (mESCs), as evidenced by teratoma and diploid chimera assays. Employing multi-omics approaches, including RNA-Seq, CUT&Tag, and ATAC-seq, the embryotoxicity mechanisms of ZnONPs were elucidated. The findings indicate that ZnONPs elevate H3K9me3 levels, leading to increased heterochromatin and consequent inhibition of gene expression related to development and pluripotency. Notably, Chaetocin, a H3K9me3 inhibitor, sucessfully reversed the embryotoxicity effects induced by ZnONPs. Additionally, the direct interaction between ZnONPs and H3K9me3 was verified through pull-down and immunoprecipitation assays. Collectively, these findings offer new insights into the epigenetic mechanisms of ZnONPs toxicity, enhancing our understanding of their impact on human reproductive health.

Interfascial planes as surgical landmarks for laparoscopic upper retroperitoneal surgery: a cadaveric and retrospectively clinical study.

Background: Radiologists currently accept the concept of "interfascial plane (IFP)" to understand retroperitoneal anatomy, replacing Meyers' classic tricompartmental theory. Despite much research on retroperitoneal anatomy, its anatomical structure, embryonic origin and developmental process still require further exploration to guide the optimization of surgical process. This study aims to explore the anatomical basis of IFP related to laparoscopic upper retroperitoneal surgery (LURS) and to compare the clinical outcomes of trans-interfascial plane procedures for LURS (TIFP-LURS) with conventional LURS (Con-LURS). Methods: The study consisted of two parts: cadaveric and clinical study. The cadaveric study involved dissecting and observing the retroperitoneal fasciae and IFP in 32 cadavers using gross anatomical and histological methods. This retrospective clinical study compared the perioperative data and complications of 229 patients who underwent TIFP-LURS and 121 patients who underwent Con-LURS for upper retroperitoneal lesions at our center. Results: The cadaveric study revealed that the retroperitoneal space was composed of multilaminar fasciae that formed potential bloodless spaces among them, that could be used as surgical landmarks and operating planes. The clinical study showed that TIFP-LURS had a significantly less estimated blood loss, lower intraoperative complication rate, lower postoperative complication rate, shorter hospital-stay and lower long-term postoperative complications rate than Con-LURS. Multivariate analysis indicated that the TIFP procedure was an independent protective factor for decreasing the risk of postoperative complications. Conclusions: The IFP are potential avascular spaces that can be used during laparoscopic surgery, and TIFP-LURS is a novel surgical approach that can improve the safety and efficacy of laparoscopic surgery for upper retroperitoneal lesions.

Video-Based Sign Language Recognition via ResNet and LSTM Network.

Sign language recognition technology can help people with hearing impairments to communicate with non-hearing-impaired people. At present, with the rapid development of society, deep learning also provides certain technical support for sign language recognition work. In sign language recognition tasks, traditional convolutional neural networks used to extract spatio-temporal features from sign language videos suffer from insufficient feature extraction, resulting in low recognition rates. Nevertheless, a large number of video-based sign language datasets require a significant amount of computing resources for training while ensuring the generalization of the network, which poses a challenge for recognition. In this paper, we present a video-based sign language recognition method based on Residual Network (ResNet) and Long Short-Term Memory (LSTM). As the number of network layers increases, the ResNet network can effectively solve the granularity explosion problem and obtain better time series features. We use the ResNet convolutional network as the backbone model. LSTM utilizes the concept of gates to control unit states and update the output feature values of sequences. ResNet extracts the sign language features. Then, the learned feature space is used as the input of the LSTM network to obtain long sequence features. It can effectively extract the spatio-temporal features in sign language videos and improve the recognition rate of sign language actions. An extensive experimental evaluation demonstrates the effectiveness and superior performance of the proposed method, with an accuracy of 85.26%, F1-score of 84.98%, and precision of 87.77% on Argentine Sign Language (LSA64).

Fermented Gracilaria lemaneiformis polysaccharides alleviate food allergy by regulating Treg cells and gut microbiota.

Food allergy has a significant impact on the health and well-being of individuals, affecting both their physical and mental states. Research on natural bioactive compounds, such as polysaccharides extracted from seaweeds, holds great promise in the treatment of food allergies. In this study, fermented Gracilaria lemaneiformis polysaccharides (F-GLSP) were prepared using probiotic fermentation. Probiotic fermentation of Gracilaria lemaneiformis reduces the particle size of polysaccharides. To compare the anti-allergic activity of F-GLSP with unfermented Gracilaria lemaneiformis polysaccharides (UF-GLSP), an OVA-induced mouse food allergy model was established. F-GLSP exhibited a significant reduction in OVA-specific IgE and mMCP levels in allergic mice. Moreover, it significantly inhibited Th2 differentiation and IL-4 production and significantly promoted Treg differentiation and IL-10 production in allergic mice. In contrast, UF-GLSP only reduced OVA-specific IgE and mMCP in the serum of allergic mice. Furthermore, F-GLSP demonstrated a more pronounced regulation of intestinal flora abundance compared to UF-GLSP, significantly influencing the populations of Firmicutes, Bacteroidetes, Lactobacillus, and Clostridiales in the intestines of mice with food allergy. These findings suggest that F-GLSP may regulate food allergies in mice through multiple pathways. In summary, this study has promoted further development of functional foods with anti-allergic properties based on red algae polysaccharides.

A non-invasive method to determine core temperature for cats and dogs using surface temperatures based on machine learning.

BACKGROUND: Rectal temperature (RT) is an important index of core temperature, which has guiding significance for the diagnosis and treatment of pet diseases. OBJECTIVES: Development and evaluation of an alternative method based on machine learning to determine the core temperatures of cats and dogs using surface temperatures. ANIMALS: 200 cats and 200 dogs treated between March 2022 and May 2022. METHODS: A group of cats and dogs were included in this study. The core temperatures and surface body temperatures were measured. Multiple machine learning methods were trained using a cross-validation approach and evaluated in one retrospective testing set and one prospective testing set. RESULTS: The machine learning models could achieve promising performance in predicting the core temperatures of cats and dogs using surface temperatures. The root mean square errors (RMSE) were 0.25 and 0.15 for cats and dogs in the retrospective testing set, and 0.15 and 0.14 in the prospective testing set. CONCLUSION: The machine learning model could accurately predict core temperatures for companion animals of cats and dogs using easily obtained body surface temperatures.

Strong Angular Oscillation of Rotationally Resolved Differential Cross Section in the H + HD → H2 + D Reaction at the Collision Energy of 2.07 eV: Evidence of Geometric Phase Effects.

Geometric phase (GP) effects in chemical reactions are subtle quantum phenomena that are challenging to identify. In this work, we report a joint experimental and theoretical study of the H + HD → H2 + D reaction at a collision energy of 2.07 eV, which is far below the energy of the conical intersection of 2.53 eV. The rotationally state-resolved differential cross sections were measured by a crossed-beam experiment with the scheme of D-atom Rydberg tagging time-of-flight detection. Experimental angular distributions of three rotational states of H2 products exhibit notable variation near the backward scattering direction. Time-dependent quantum mechanics calculations (TDQMs) were carried out at the same collision energy, with and without the inclusion of GP. The experimental angular distributions are in good agreement with TDQM results with the inclusion of GP but do not agree with TDQM results without the inclusion of GP. This work demonstrates the existence of GP effects at energy far below the conical intersection.

Allogeneic haematopoietic stem cell transplantation for adult T-lymphoblastic lymphoma: A real-world multicentre analysis in China.

In this multicentre, real-world study, we aimed to identify the clinical outcomes and safety of allogeneic haematopoietic stem cell transplantation (allo-HSCT) in T-lymphoblastic lymphoma (T-LBL). A total of 130 Ann Arbor stage III or IV T-LBL patients (>16 years) treated with allo-HSCT across five transplant centres were enrolled. The 2-year cumulative incidence of disease progression, the probabilities of progression-free survival (PFS), overall survival (OS) and non-relapse mortality (NRM) after allo-HSCT were 21.0%, 69.8%, 79.5% and 9.2% respectively. Patients with central nervous system (CNS) involvement had a higher cumulative incidence of disease progression compared with those without CNS involvement (57.1% vs. 18.9%, HR 3.78, p = 0.014). Patients receiving allo-HSCT in non-remission (NR) had a poorer PFS compared with those receiving allo-HSCT in complete remission (CR) or partial remission (49.2% vs. 72.7%, HR 2.21, p = 0.041). Particularly for patients with bone marrow involvement and achieving CR before allo-HSCT, measurable residual disease (MRD) positivity before allo-HSCT was associated with a poorer PFS compared with MRD negativity (62.7% vs. 86.8%, HR 1.94, p = 0.036). On multivariate analysis, CNS involvement at diagnosis and receiving allo-HSCT in NR were associated with disease progression. Thus, our real-world data suggested that allo-HSCT appeared to be an effective therapy for adult T-LBL patients with Ann Arbor stage III or IV disease.

Genetic alterations and allele frequency of BRAF V600E and TERT mutation in papillary thyroid carcinoma with intermediate-to-high recurrence risk: a retrospective study.

The predictive value of allele frequency (AF) of BRAF V600E and TERT mutations in papillary thyroid carcinoma (PTC) remains controversial. We aimed to investigate the AF of BRAF V600E and TERT mutations in intermediate-to-high risk PTC and their association between tumor invasiveness, prognosis, and other mutations. Probe hybridization capture and high-throughput sequencing were used to quantitatively test 40 gene loci in 94 intermediate-to-high recurrence risk PTC patients, combined with clinical characteristics and follow-up for retrospective analysis. BRAF V600E mutation AF was linked to a increased risk of thyroid capsule penetration, recurrence, and concurrent mutations. Concurrent mutations could lead to a worse prognosis and increased invasiveness. TERT promoter mutation frequently accompanied other mutations and resulted in a poorer prognosis. However, there was no clear association between the TERT mutation AF and tumor invasiveness or recurrence. The sensitivity and specificity of predicting recurrence in intermediate-to-high risk PTC with BRAF V600E mutation AF > 28.2% were 60 and 80%. Although genetic alterations in PTC can differ among different ethnicities, the AF of BRAF V600E and TERT mutations may be similar. The AF of BRAF V600E has the potential to be a novel indicator in predicting PTC invasiveness and prognosis.

The neural representations of valence transformation in indole processing.

Indole is often associated with a sweet and floral odor typical of jasmine flowers at low concentrations and an unpleasant, animal-like odor at high concentrations. However, the mechanism whereby the brain processes this opposite valence of indole is not fully understood yet. In this study, we aimed to investigate the neural mechanisms underlying indole valence encoding in conversion and nonconversion groups using the smelling task to arouse pleasantness. For this purpose, 12 conversion individuals and 15 nonconversion individuals participated in an event-related functional magnetic resonance imaging paradigm with low (low-indole) and high (high-indole) indole concentrations in which valence was manipulated independent of intensity. The results of this experiment showed that neural activity in the right amygdala, orbitofrontal cortex and insula was associated with valence independent of intensity. Furthermore, activation in the right orbitofrontal cortex in response to low-indole was positively associated with subjective pleasantness ratings. Conversely, activation in the right insula and amygdala in response to low-indole was positively correlated with anticipatory hedonic traits. Interestingly, while amygdala activation in response to high-indole also showed a positive correlation with these hedonic traits, such correlation was observed solely with right insula activation in response to high-indole. Additionally, activation in the right amygdala in response to low-indole was positively correlated with consummatory pleasure and hedonic traits. Regarding olfactory function, only activation in the right orbitofrontal cortex in response to high-indole was positively correlated with olfactory identification, whereas activation in the insula in response to low-indole was negatively correlated with the level of self-reported olfactory dysfunction. Based on these findings, valence transformation of indole processing in the right orbitofrontal cortex, insula, and amygdala may be associated with individual hedonic traits and perceptual differences.

Tumor characteristics, brain functional activity, and connectivity of tinnitus in patients with vestibular schwannoma: a pilot study.

Background: The mechanism underlying tinnitus remains unclear, and when it coexists with vestibular schwannoma (VS), it can significantly diminish the quality of life for affected patients. This study aimed to determine the correlation between preoperative clinical characteristics of VS, postoperative changes in brain function, and tinnitus in patients with VS through a cohort study. Methods: We collected data from 80 patients with VS preoperatively and 28 patients with VS preoperatively and postoperatively, and recruited 28 healthy controls. We used Chi-squared tests and unpaired t-tests to identify clinical characteristics with a significant preoperative effect. We used paired t-tests to identify brain regions where patients demonstrated significant changes in amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) postoperatively. Tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI) and Visual Analogue Scale (VAS). Pearson correlation coefficients were applied to assess the relationship between the changes in ALFF and ReHo and the changes in THI and VAS scores postoperatively. We also conducted seed- and region of interest (ROI)-based functional connectivity (FC) analyses. Results: Before surgery, patients with VS with tinnitus (n=49) had smaller tumors (t=3.293; P<0.001), more solid tumor (χ2=4.559; P=0.033), and less extrusion into the cerebellum brain stem (χ2=10.345; P=0.001) than those without tinnitus (n=31). After surgery, the 28 patients with VS showed a significant reduction in ALFF in the left Cerebellum_Crus2 (a lobule in the cerebellum anatomy) (ROI 1) and a significant reduction in ReHo in the left Cerebellum_Crus1 (a lobule in the cerebellum anatomy) (ROI 2) and the right precuneus (ROI 3). Conversely, ReHo was significantly increased in the right precentral gyrus (ROI 4) [cluster-level P value family-wise error (PFWE) <0.05]. The changes in ALFF values were negatively correlated with changes in the VAS score (r=-0.32; P<0.05). The FC strengths of patients between ROI 2 and the left and right posterior cingulate gyrus were significantly decreased postoperatively [false discovery rate (FDR) correction; P<0.05]. Conclusions: Preoperative tinnitus in patients with VS may be influenced by tumor characteristics. The functional activities of brain regions are possibly altered postoperatively, which may be involved in the maintenance of postoperative tinnitus. Notably, the changes in ALFF are correlated with tinnitus.