Taste receptor type 1 (T1r) proteins are responsible for recognizing nutrient chemicals in foods. In humans, T1r2/T1r3 and T1r1/T1r3 heterodimers serve as the sweet and umami receptors that recognize sugars or amino acids and nucleotides, respectively. T1rs are conserved among vertebrates, and T1r2a/T1r3 from medaka fish is currently the only member for which the structure of the ligand-binding domain (LBD) has been solved. T1r2a/T1r3 is an amino acid receptor that recognizes various l-amino acids in its LBD as observed with other T1rs exhibiting broad substrate specificities. Nevertheless, the range of chemicals that are recognized by T1r2a/T1r3LBD has not been extensively explored. In the present study, the binding of various chemicals to medaka T1r2a/T1r3LBD was analyzed. A binding assay for amino acid derivatives verified the specificity of this protein to l-α-amino acids and the importance of α-amino and carboxy groups for receptor recognition. The results further indicated the significance of the α-hydrogen for recognition as replacing it with a methyl group resulted in a substantially decreased affinity. The binding ability to the protein was not limited to proteinogenic amino acids, but also to non-proteinogenic amino acids, such as metabolic intermediates. Besides l-α-amino acids, no other chemicals showed significant binding to the protein. These results indicate that all of the common structural groups of α-amino acids and their geometry in the l-configuration are recognized by the protein, whereas a wide variety of α-substituents can be accommodated in the ligand binding sites of the LBDs.

We report a case of anti-NMDAR encephalitis and residual mutism in a 23-year-old woman who presented with neuroleptic intolerance. Admission to our department for investigation of her abnormal behavior revealed cerebrospinal fluid (CSF) positivity for anti-NMDAR antibodies, and the patient underwent immunotherapy. However, generalized tonic seizures developed, requiring mechanical ventilation in the intensive care unit. Antipsychotic drugs were also administered for involuntary movements and insomnia. Thereafter, a malignant syndrome of severe hyperCKemia (Max: 191,120 IU/L) and shock developed, requiring resuscitation and three sessions of hemodialysis. Subsequent rituximab therapy led to improvement, except for mutism, which had newly developed during resuscitation. Seven months after initial admission, the patient was discharged with independent gait. However, her mutism still persists. Temporary mutism has been reported to occur in this type of encephalitis, albeit rarely. The fact that remission was not observed in this case may have been due to cerebellar infarction occurring during resuscitation, but the true cause remains unclear. Malignant syndrome or rhabdomyolysis, as seen in this patient, has also sometimes been reported in this form of encephalitis when antipsychotic agents, especially dopamine receptor blockers, have been administered. Therefore, such agents should be administered with caution in patients with anti-NMDAR encephalitis. (Received August 17, 2023; Accepted October 24, 2023; Published March 1, 2024).

Nicotine exposure from smoking constitutes a significant global public health concern. Furthermore, smoking represents a pivotal risk factor for head and neck squamous cell carcinoma (HNSCC). However, the influence of nicotine on HNSCC remains relatively underexplored. Our aim was to unravel the molecular mechanisms that underlie the effect of nicotine on the metastatic cascade of HNSCC. In this study, we discovered a significant association between smoking and HNSCC metastasis and prognosis. Nicotine significantly enhanced HNSCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Analysis of TCGA-HNSCC and FDEENT-HNSCC cohorts revealed reduced miR-375-3p levels in HNSCC tumor tissues, particularly among current smokers. Additionally, miR-375-3p level was strongly correlated with both lymph node metastasis and tumor stage. By downregulating miR-375-3p, nicotine promotes HNSCC cell metastasis in vitro and hematogenous metastatic capacity in vivo. Utilizing transcriptomic sequencing, molecular docking, dual-luciferase reporter assay, and fluorescence in situ hybridization (FISH), we demonstrated that miR-375-3p specifically binds to 3\' untranslated region (3\'UTR) of NTRK2 mRNA. Thus, this study uncovers a novel nicotine-induced mechanism involving miR-375-3p-mediated NTRK2 targeting, which promotes HNSCC metastasis. These findings have implications for improving the prognosis of patients with HNSCC, especially in smokers.

OBJECTIVE: Our study aims to examine the risk factors for comorbid psychosis in pediatric patients hospitalized for anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and its impact on hospital outcomes.
METHODS: We conducted a cross-sectional study using the nationwide inpatient sample (NIS 2018-2019). We included 3,405 pediatric inpatients (age 6-17 years) with a primary discharge diagnosis of anti-NMDAR encephalitis. We used binomial logistic regression model to evaluate the odds ratio (OR) of variables (demographic and comorbidities) associated with comorbid psychosis.
RESULTS: The prevalence of comorbid psychosis in anti-NMDAR encephalitis inpatients was 5.3%, and majorly constituted of adolescents (72.2%) and females (58.3%). In terms of race, Blacks (OR 2.41), and Hispanics (OR 1.80) had a higher risk of comorbid psychosis compared to Whites. Among comorbidities, encephalitis inpatients with depressive disorders (OR 4.60), sleep-wake disorders (OR 3.16), anxiety disorders (OR 2.11), neurodevelopmental disorders (OR 1.95), and disruptive behavior disorders (OR 2.15) had a higher risk of comorbid psychosis. Anti-NMDAR encephalitis inpatients with comorbid psychosis had a longer median length of stay at 24.6 days (vs. 9.8 days) and higher median charges at $262,796 (vs. $135,323) compared to those without psychotic presentation.
CONCLUSIONS: Adolescents, females, and Blacks with encephalitis have a higher risk of psychotic presentation leading to hospitalization for anti-NMDAR encephalitis. Identification of demographic predictors and comorbidities can aid in early recognition and intervention to optimize care and potentially reduce the healthcare burden.

Selective tropomyosin receptor kinase (TRK) inhibitors are approved targeted therapies for patients with solid tumors harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. Country-specific estimates of NTRK gene fusion frequency, and knowledge on the characteristics of affected patients, are limited. We identified patients with histologically-confirmed papillary thyroid cancer (PTC) from Finland\'s Auria Biobank. TRK protein expression was determined by pan-TRK immunohistochemistry. Immuno-stained tumor samples were scored by a certified pathologist. Gene fusions and other co-occurring gene alterations were identified by next generation sequencing. Patient characteristics and vital status were determined from linked hospital electronic health records (EHRs). Patients were followed from 1 year before PTC diagnosis until death. 6/389 (1.5%) PTC patients had an NTRK gene fusion (all NTRK3); mean age 43.8 years (and none had comorbidities) at PTC diagnosis. Gene fusion partners were EML4 (n = 3), ETV6 (n = 2), and RBPMS (n = 1). Of 3/6 patients with complete EHRs, all received radioactive iodine ablation only and were alive at end of follow-up (median observation, 9.12 years). In conclusion, NTRK gene fusion is infrequent in patients with PTC. Linkage of biobank samples to EHRs is feasible in describing the characteristics and outcomes of patients with PTC and potentially other cancer types.

OBJECTIVE: The neurotrophic tyrosine receptor kinase (NTRK) fusion transcript (FT) is a major genetic landmark of infantile fibrosarcoma (IFS) and cellular congenital mesoblastic nephroma (cCMN) but is also described in other tumours. The recent availability of NTRK-targeted drugs enhances the need for better identification. We aimed to describe the anatomic locations and imaging features of tumours with NTRK-FT in children.
METHODS: Imaging characteristics of NTRK-FT tumours of 41 children (median age: 4 months; 63% <1 year old; range: 0-188) managed between 2001 and 2019 were retrospectively analysed. The tumours were located in the soft tissues (n = 24, including 19 IFS), kidneys (n = 9, including 8 cCMN), central nervous system (CNS) (n = 5), lung (n = 2), and bone (n = 1). The tumours were frequently deep-located (93%) and heterogeneous (71%) with necrotic (53%) or haemorrhagic components (29%). Although inconstant, enlarged intratumoural vessels were a recurrent finding (70%) with an irregular distribution (63%) in the most frequent anatomical locations.
CONCLUSIONS: Paediatric NTRK-FT tumours mainly occur in infants with very variable histotypes and locations. Rich and irregular intra-tumoural vascularization are recurrent findings.
CONCLUSIONS: Apart from IFS of soft tissues and cCMN of the kidneys, others NTRK-FT tumours locations have to be known, as CNS tumours. Better knowledge of the imaging characteristics may help guide the pathological and biological identification.

暂无摘要。

OBJECTIVE: Teratoma is a type of germ cell tumor that derived from early embryonic stem cells and germ cell lines, which can lead to a rare complication known as paraneoplastic encephalitis syndrome. Delayed removal of teratoma allows for continuing antigen presentation, inducing affinity maturation of the antibody and the generation of long-lived plasma cells that infiltrate both bone marrow and brain, which makes the patient nonresponsive to later removal of teratoma and refractory to immunotherapy. We present this rare case to remind clinicians to be vigilant for the recognition and removal of teratoma during the treatment of autoimmune encephalitis.
METHODS: We retrospectively reviewed the clinical record of this 12-year 5-month-old female patient diagnosed with anti- N -methyl- d -aspartate receptor (anti-NMDAR) autoimmune encephalitis; her ovarian teratoma was unidentified on admission. She did not respond to immunosuppressive therapy until the mature ovarian teratoma identified 45 days after admission and removed the following day, nearly 2 months after symptom onset. This patient experienced nearly complete resolution of symptoms within the subsequent 2 weeks. In addition, we conducted a literature review of the clinical presentations and treatment of anti-NMDAR autoimmune encephalitis associated with ovarian teratoma in the pediatric population.
RESULTS: Our findings suggest that clinicians should be vigilant for the recognition and removal of teratoma during the treatment of autoimmune encephalitis.
CONCLUSIONS: Female pediatric patients with suspected anti-NMDAR encephalitis should be screened for ovarian tumors immediately and treated in a multidisciplinary setting including neurology and obstetrics and gynecology.

暂无摘要。

OBJECTIVE: To characterize the clinical and radiological features, treatment responses and outcomes of children with co-existing anti-N-methyl-D-aspartate receptor(NMDAR) and myelin oligodendrocyte glycoprotein(MOG) antibody-associated encephalitis.
METHODS: Clinical manifestations, imaging features, effectiveness of treatment and outcomes of patients who were cerebral spinal fluid(CSF)-positive for NMDAR-antibody(NMDAR-ab) and seropositive for MOG-antibody(MOG-ab) were analyzed.
RESULTS: Twelve patients including 8 females and 4 males were enrolled. The median onset age was 9 years, ranging from 2.2 to 12.8 years. Behavioral changes and/or psychiatric symptoms (n = 8/12), seizures (n = 8/12), encephalopathy (n = 7/12) were 3 of the most common symptoms. Brain magnetic resonance imaging(MRI) of all the patients showed T2/fluid attenuation inversion recovery(FLAIR) abnormal signal in the cerebral white matter at least once in the courses of disease, 2 of whom developed new brain lesions which were asymptomatic. All of the patients had supratentorial lesions. Spinal cord MRI was performed in 7 patients. Only 1 patient showed related abnormalities with increased T2 signal in the spinal cord C1-5. Nine patients underwent optic nerve MRI; 5 patients demonstrated abnormal results, among whom 4 exhibited T2 abnormal signal (2 were symptom-free) and 1 showed a little effusion in bilateral optic nerve sheats. Intravenous immunoglobulin (IVIG) and intravenous methylprednisolone (IVMP) were the most common used therapies in those patients. Nine patients were treated with second-line therapy to prevent relapses. For total 29 clinical attacks, the median modified Rankin Scale (mRS) before treatment and after therapy of acute stage was 1 and 0, respectively. Seven of 12 patients(58.3 %) experienced clinical relapses. In terms of outcome, all of the patients\' mRS of last follow-up (≥6 months) was ≤2.
CONCLUSIONS: Behavioral changes and/or psychiatric symptoms, seizures and encephalopathy were common in children with co-existing anti-NMDAR and MOG antibody-associated encephalitis. A minority of subjects may develop asymptomatic lesions on brain and optic nerve MRI. The relapse rate of this disease is relatively high. The majority of patients responded well to the immunotherapies and had a good outcome(mRS of last follow-up≤2).