Long-term outcomes of neuroendoscopic cyst partial resection combined with stereotactic radiotherapy for craniopharyngioma.

PURPOSE: The aim of this study was to evaluate the treatment outcomes of neuroendoscopic cyst partial resection (ECPR) combined with stereotactic radiotherapy (SRT) for cystic craniopharyngiomas. METHODS: In this retrospective study, 22 craniopharyngioma patients undergoing ECPR combined with SRT were included. This combination therapy was indicated for suprasellar cystic craniopharyngiomas in patients whose pituitary function was preserved but would be difficult to preserve in direct surgery. The outcomes of combination therapy, including tumor control and postoperative visual and pituitary functions, were investigated. RESULTS: ECPR was safely performed, and cyst shrinkage was accomplished in all cases. After ECPR, visual function improved in 12 of 13 patients (92%) with visual field disturbance and did not deteriorate in any patients. Pituitary function was preserved in 14 patients (64%) and deteriorated in eight patients (36%) after ECPR. As a complication of ECPR, meningitis occurred because of a wound infection in one patient. In 18 of 22 patients (82%), the tumor was controlled without further treatment 19 - 87 months (median, 33 months) after SRT. Hypopituitarism was an adverse event after SRT in two of the 18 patients who achieved tumor control. Four patients (18%) had enlarged cysts after SRT. Postoperative pituitary function was significantly more likely to deteriorate in cases of extensive detachment from the ventricular wall, and retreatment was significantly more common in cases with hypothalamic extension. CONCLUSION: Although limited to some cases, ECPR combined with SRT is a less invasive and useful therapeutic option for suprasellar cystic craniopharyngiomas. However, its long-term prognosis requires further evaluation.

Vanillin production by Corynebacterium glutamicum using heterologous aromatic carboxylic acid reductases.

BACKGROUND: Vanillin is a flavoring substance derived from vanilla. We are currently developing a biotransformation method for vanillin production using glucose. This report describes the last step in vanillin production: the conversion of vanillic acid to vanillin. First, we selected Corynebacterium glutamicum as the host owing to its high vanillin resistance. The aromatic aldehyde reductase gene (NCgl0324) and vanillic acid demethylase protein subunits A and B gene (vanAB, NCgl2300-NCgl2301) were deleted in C. glutamicum genome to avoid vanillin degradation. Next, we searched for an aromatic carboxylic acid reductase (ACAR), which converts vanillic acid to vanillin. Seventeen ACAR homologs from various organisms were introduced into C. glutamicum. RESULTS: In vivo conversion experiments showed that eight ACARs were successfully expressed and produced vanillin. In terms of conversion activity and substrate specificity, the ACARs from Gordonia effusa, Coccomyxa subellipsoidea, and Novosphingobium malaysiense are promising candidates for commercial production. CONCLUSIONS: Corynebacterium glutamicum harboring Gordonia effusa ACAR produced 22 g/L vanillin, which is, to the best of our knowledge, the highest accumulation reported in the literature. At the same time, we discovered ACAR from Novosphingobium malaysiense and Coccomyxa subellipsoidea C-169 with high substrate specificity. These findings are useful for reducing the byproducts.

Lifelong cardiovascular care in Turner syndrome: two cases with review of literature.

Cardiovascular disease is one of the most important complications in girls and women with Turner syndrome (TS). Although the latest international guideline provides useful suggestions for the management of cardiovascular diseases in TS, some unknown cardiac conditions warrant physicians' attention and awareness. Here, we have reported two adult cases wherein significant cardiovascular diseases were detected during the transition period. The first case patient was diagnosed with aortic crank deformity and left subclavian artery aneurysm at 14 years based on the report of cardiac catheterization, computed tomography angiography, and cardiac magnetic resonance imaging, which had remained undetected by annual evaluations using transthoracic echocardiography (TTE). This case emphasizes the importance of cardiac reevaluation during the transition period. The second case patient was diagnosed with moderate mitral valve regurgitation (MR) due to mitral valve prolapse at 18 years through TTE, although the first evaluation at 7 years by TTE detected slight MR without any clinical concerns. The condition however progressed to severe MR at 28 years, requiring mitral valvuloplasty. MR is the most common valve disease worldwide, which makes it challenging to comprehend whether the condition is a complication. However, the condition requiring surgery at this age is extremely rare, which implies the possibility of early progression. Because almost all literature on cardiovascular complications in TS is cross-sectional, further information about longitudinal cardiovascular conditions is vital for optimal care for girls and women with TS. The two cases reported in this article provide significant information for improving lifelong cardiovascular health issues in TS.

Phosphorylation of α-synuclein at T64 results in distinct oligomers and exerts toxicity in models of Parkinson's disease.

α-Synuclein accumulates in Lewy bodies, and this accumulation is a pathological hallmark of Parkinson's disease (PD). Previous studies have indicated a causal role of α-synuclein in the pathogenesis of PD. However, the molecular and cellular mechanisms of α-synuclein toxicity remain elusive. Here, we describe a novel phosphorylation site of α-synuclein at T64 and the detailed characteristics of this post-translational modification. T64 phosphorylation was enhanced in both PD models and human PD brains. T64D phosphomimetic mutation led to distinct oligomer formation, and the structure of the oligomer was similar to that of α-synuclein oligomer with A53T mutation. Such phosphomimetic mutation induced mitochondrial dysfunction, lysosomal disorder, and cell death in cells and neurodegeneration in vivo, indicating a pathogenic role of α-synuclein phosphorylation at T64 in PD.

Investigation of appropriate needle length considering skin thickness with the real injection posture for insulin injections in diabetic patients.

BACKGROUND: Insulin treatment is widely used not only for type 1 but also for type 2 diabetes patients. Insulin must be injected into the subcutaneous tissue to be effective. The needle length has been shortened for safety and efficiency. However, whether patients use an appropriate needle length is unclear. METHODS: Skin thickness was measured by ultrasound with patients in their usual posture during injection. Furthermore, the effect of the intervention in which the needle length was changed was investigated. RESULTS: Thirty-eight percent of the patients had fluid leakage and injected the needle intradermally. The average skin thickness was 3.3 mm while sitting, which was greater than that in a previous report including measurements taken while lying down. Consequently, the skin thickness was > 4 mm in 9.5% of the patients who used 4-mm needles. Cases of leakage and intradermal injection decreased when the needle length was changed. CONCLUSIONS: This study identified that the needle length should be considered in patients with thick skin or a lower body mass index due to possibility of intradermal injection.

Transverse and longitudinal right ventricular fractional parameters derived from four-chamber cine MRI are associated with right ventricular dysfunction etiology.

Studies of the usefulness of transverse right ventricular (RV) shortening are limited. We retrospectively analyzed the CMR images of 67 patients (age: 50.8 ± 19.0 years; men: 53.7%; Control: n = 20, Overloaded RV (atrial septal defect): n = 15, Constricted RV (pericarditis): n = 17, Degenerated RV (arrhythmogenic right ventricular cardiomyopathy): n = 15) (all enrolled consecutively for each disease) in a single center. We defined RV longitudinal (fractional longitudinal change: FLC) and transverse (fractional transverse change: FTC) contraction parameters. We assessed the FTC/FLC (T/L) ratio on four-chamber cine CMR views and compared the four groups regarding the fractional parameters. FTC had a stronger correlation (R2 = 0.650; p < 0.001) with RV ejection fraction than that with FLC (R2 = 0.211; p < 0.001) in the linear regression analysis. Both FLC and FTC were significantly lower in the Degenerated RV and Constricted RV groups compared with those in the Control and Overloaded RV groups. The T/L ratio was significantly lower in the Degenerated RV group (p = 0.008), while the Overloaded RV (p = 0.986) and Constricted RV (p = 0.582) groups had preserved T/L ratios, compared with the Control group. Transverse shortening contributes to RV function more significantly compared with longitudinal contraction. Impaired T/L ratios may reflect RV myocardial degeneration. RV fractional parameters may help precisely understand RV dysfunction.

Giant Cell Tumor of Bone Without Giant Cells with a Long Clinical Course: A Case Report.

Giant cell tumor of bone (GCTB) consists of a mixture of neoplastic mononuclear cells and non-neoplastic cells, including polynuclear giant cells. Recently, with the spread of the immunohistochemical staining marker H3.3 G34W corresponding to specific genetic abnormalities, the histological diversity of GCTB has been recognized. GCTB without giant cells is uncommon, although it has also been reported previously. Herein, we describe a 45-year-old man with GCTB without giant cells who was successfully diagnosed using H3.3 G34W immunohistochemistry. Other unusual findings in GCTB that were identified in this patient include bone and osteoid formation with a long clinical course of 13 years. We also compared the histological findings of the current patient to those who received denosumab therapy.

Rhabdomyosarcoma With FUS::TFCP2 Fusion in the Scalp: A Rare Case Report Depicting Round and Spindle cell Morphology.

Rhabdomyosarcoma (RMS) is a nonepithelial malignant tumor that differentiates into immature skeletal muscle. It is currently classified into 4 main subtypes according to the WHO classification. However, based on clinicopathological and molecular findings, there has been an increasing number of cases that do not fit into any of these subtypes. TFCP2-rearranged RMS is a rare tumor with characteristic clinicopathological findings including a preference for the craniofacial bones, a spindle and epithelioid histomorphology, and positive immunohistochemistry for epithelial markers, ALK, and myogenic markers. In this report, we describe a rare case of RMS with FUS::TFCP2 fusion in the scalp of a 58-year-old man. Histologically, the tumor showed a biphasic pattern, with solid proliferation of round cells in the superficial areas and of spindle cells in the deep areas. Immunohistochemically, tumor cells were positive for pan keratin, myogenic markers (desmin, MYOD1, and myogenin), and ALK. Additionally, fluorescence in situ hybridization using a break-apart FUS probe revealed FUS rearrangement. RMS with FUS::TFCP2 fusion was suspected, and the fusion gene was finally confirmed by target fusion sequencing. We believe that detailed histological, immunohistochemical, and genetic findings were important for the diagnosis. The unique traits of this tumor were the biphasic histological appearance consisting of round and spindle cells and development in the skin and soft tissue.

Post-Marketing Surveillance Study of the Safety and Efficacy of Nalfurafine (Capsules 2.5 µg, Oral Dispersing Tablets 2.5 µg) in 1186 Patients with Chronic Liver Disease and Intractable Pruritus.

Background: Nalfurafine (Remitch®, Toray Industries, Inc.) is a selective κ-receptor agonist approved in Japan for the improvement of pruritus in patients with chronic liver diseases (only when existing treatments bring insufficient efficacy) in May 2015. Methods: A post-marketing Specific Drug Use Survey was conducted in Japan (March 1, 2016 to June 30, 2020) of the safety and efficacy of nalfurafine for the improvement of pruritus in patients with chronic liver disease. Results: Among 1186 cases analyzed for safety, the incidence of adverse drug reactions was 9.4% (112/1186 cases), lower than 61.4% reported in pre-marketing surveillance (297/484 cases). No specific safety issues were found and no cases of concern for drug dependence identified. Efficacy (itch improvement) was demonstrated in 73.16% (815/1114 cases; 12-week analysis set) and in 85.67% (520/607; general assessment of itch improvement at 1-year analysis set). A significant difference was found in 4 items of itch improvement at 12 weeks and 8 items of itch improvement at 1 year. No noteworthy issues were identified. Mean Visual Analog Scale (VAS) values after 12 weeks and 1 year after the first dose were significantly lower than the baseline (p < 0.0001 for both treatment durations). Mean severity scores (Kawashima's classification scheme) were significantly lower than the pretreatment score at 12 weeks and 1 year after the first dose (both p < 0.0001). No concerns were identified in the efficacy and safety of nalfurafine in patients with specific background, ie, the elderly (aged ≥ 65 years), those with renal impairment, and those on long-term treatment (≥ 365 days) compared with patients without corresponding background. Conclusion: No new safety issues of concern or cases of insufficient efficacy were identified in this Specific Drug Use Survey of the safety and efficacy of nalfurafine for the improvement of pruritus in patients with chronic liver diseases.

Surgery for Thyroid Cancer Invading the Trachea.

Thyroid cancer invading the trachea can be asymptomatic, but when tumour invasion reaches the mucosal surface, it causes bloody sputum and dyspnoea. The treatment plan for thyroid cancer is determined based on the site, depth, and extent of the invasion. Different from tumours arising from the tracheal mucosa, in thyroid cancer, invasion begins outside the airway and progresses toward the lumen, making it difficult to accurately diagnose the extent of the invasion even with bronchoscopy. Therefore, surgeons must determine the range of resection during surgery. Invasion reaching the tracheal mucosa requires full-thickness resection and is performed using tracheal window resection combined with tracheocutaneous fistula or tracheal sleeve resection followed by end-to-end anastomosis. The airway is safely secured with window resection, but closing the tracheal stoma often requires multi-stage reconstruction. Sleeve resection is an oncologically appropriate surgical method that can be completed in one stage, although there is a risk of serious complications associated with anastomotic dehiscence. Since well-differentiated thyroid cancer progresses slowly, some degree of survival can be expected even with incomplete resection. However, when shaving is performed for tumours with deep invasion that reaches the tracheal mucosa, the residual tumour tissue continues to grow steadily and eventually leads to airway stenosis. Since reoperation for tracheal resection is difficult, radical full-thickness resection should be performed in the initial surgery. Although this surgical intervention is far more demanding for both patients and surgeons than shaving, the procedure eventually improves patient's prognosis and quality of life.

Inter-Brain Synchronization During Sandplay Therapy: Individual Analyses.

Interactions between the client (Cl) and therapist (Th) evolve therapeutic relationships in psychotherapy. An interpersonal link or therapeutic space is implicitly developed, wherein certain important elements are expressed and shared. However, neural basis of psychotherapy, especially of non-verbal modalities, have scarcely been explored. Therefore, we examined the neural backgrounds of such therapeutic alliances during sandplay, a powerful art/play therapy technique. Real-time and simultaneous measurement of hemodynamics was conducted in the prefrontal cortex (PFC) of Cl-Th pairs participating in sandplay and subsequent interview sessions through multichannel near-infrared spectroscopy. As sandplay is highly individualized, and no two sessions and products (sandtrays) are the same, we expected variation in interactive patterns in the Cl-Th pairs. Nevertheless, we observed a statistically significant correlation between the spatio-temporal patterns in signals produced by the homologous regions of the brains. During the sandplay condition, significant correlations were obtained in the lateral PFC and frontopolar (FP) regions in the real Cl-Th pairs. Furthermore, a significant correlation was observed in the FP region for the interview condition. The correlations found in our study were explained as a "remote" synchronization (i.e., unconnected peripheral oscillators synchronizing through a hub maintaining free desynchronized dynamics) between two subjects in a pair, possibly representing the neural foundation of empathy, which arises commonly in sandplay therapy (ST).

Age-related demethylation of the TDP-43 autoregulatory region in the human motor cortex.

In amyotrophic lateral sclerosis (ALS), TAR DNA-binding protein 43 (TDP-43), which is encoded by TARDBP, forms aggregates in the motor cortex. This aggregate formation may be triggered by an increase in the TDP-43 level with aging. However, the amount of TDP-43 is autoregulated by alternative splicing of the TARDBP 3'UTR, and how this autoregulation is affected by aging remains to be elucidated. We found that DNA demethylation in the autoregulatory region in the TARDBP 3'UTR reduced alternative splicing and increased TARDBP mRNA expression. Furthermore, in the human motor cortex, we found that this region was demethylated with aging, resulting in increased expression of TARDBP mRNA. The acceleration of DNA demethylation in the motor cortex was associated with the age of ALS onset. In summary, the dysregulation of TDP-43 autoregulation by age-related DNA demethylation in the motor cortex may explain the contribution of aging and motor system selectivity in ALS.

The first survey about women doctors in the Japanese Society for Pediatric Endocrinology (JSPE).

The Career Development for Women Pediatric Endocrinologists and Work-Life Balance Committee and Support Team for Women Doctors in Education and Training Committee investigated the current situation of women doctors in the Japanese Society for Pediatric Endocrinology (JSPE). The proportion of women doctors (PWD) was as follows. 1) Members of JSPE: 40.2% in fiscal 2018, versus 33.3% in fiscal 2010; 2) councilors: 21.6% from fiscal 2014 to 2017, versus 6.3% from fiscal 2008 to 2010; 3) board members: 13.6% from fiscal 2014 to 2017, versus 0% from fiscal 2008 to 2010; 4) board-certified endocrinologists (Pediatrics) and certified endocrine educators (Pediatrics): 31.7% and 25.4% in fiscal 2018, versus 22.4% and 15.3% in fiscal 2010, respectively; and 5) average value of first presenters and chairpersons in the Annual Scientific Meeting of JSPE was 41.4% and 22.3% from 2010 to 2019. These PWD figures for JSPE were higher than those of the Japan Pediatric Society and the Japan Endocrine Society, indicating a reducing gender gap in JSPE, although increases in the PWD of decision-making posts remains insufficient.

Clarithromycin As an Alternative and Prophylactic Agent in a Hematopoietic Stem Cell Transplantation Patient.

BACKGROUND Nocardia infections have rarely been reported in hematopoietic stem cell transplantation (HSCT) patients, who usually receive the prophylactic use of sulfamethoxazole/trimethoprim (ST) against Pneumocystis jiroveci. However, the ST prophylaxis, sensitive to Nocardia species, sometimes induces renal toxicities. Therefore, alternative prophylactic or therapeutic drugs are required for nocardiosis in HSCT patients. CASE REPORT A 34-year-old Japanese man with acute mixed phenotypic leukemia with t(9; 22) received allogenic peripheral blood HSCT from a haplo-identical sibling donor. He developed graft versus host disease (GVHD) with grade II, and was treated with prednisolone and cyclosporine A with concurrent ciprofloxacin, fluconazole, valacyclovir, and ST. However, the prophylactic ST was ceased because of its renal toxicity. He developed a pulmonary nodular lesion with elevated ß-D-glucan and Aspergillus galactomannan antigen. Repeated blood and sputum culture isolated no pathogens. Voriconazole treatment administered once improved these lesions and laboratory findings. One month later, he presented with right pleuritic chest pain and multiple ring-enhancing cavitation lesions along the ribs. A needle biopsy demonstrated Nocardia elegans, which is an extremely rare infection induced by Nocardia species, in the cavitation lesions, shown by 16S rRNA gene sequencing. He was started on doripenem and liposomal amphotericin B, and a subsequent treatment kept him free from Nocardia elegans infection, without any adverse effects, while continuing the cyclosporine A and prednisolone treatment for chronic GVHD. CONCLUSIONS Clarithromycin has fewer adverse effects than ST. This case suggests that clarithromycin is an appropriate alternative and prophylactic therapy for patients with nocardiosis and ST toxicities.

Cytosolic dsDNA of mitochondrial origin induces cytotoxicity and neurodegeneration in cellular and zebrafish models of Parkinson's disease.

Mitochondrial dysfunction and lysosomal dysfunction have been implicated in Parkinson's disease (PD), but the links between these dysfunctions in PD pathogenesis are still largely unknown. Here we report that cytosolic dsDNA of mitochondrial origin escaping from lysosomal degradation was shown to induce cytotoxicity in cultured cells and PD phenotypes in vivo. The depletion of PINK1, GBA and/or ATP13A2 causes increases in cytosolic dsDNA of mitochondrial origin and induces type I interferon (IFN) responses and cell death in cultured cell lines. These phenotypes are rescued by the overexpression of DNase II, a lysosomal DNase that degrades discarded mitochondrial DNA, or the depletion of IFI16, which acts as a sensor for cytosolic dsDNA of mitochondrial origin. Reducing the abundance of cytosolic dsDNA by overexpressing human DNase II ameliorates movement disorders and dopaminergic cell loss in gba mutant PD model zebrafish. Furthermore, IFI16 and cytosolic dsDNA puncta of mitochondrial origin accumulate in the brain of patients with PD. These results support a common causative role for the cytosolic leakage of mitochondrial DNA in PD pathogenesis.

Renal morphology and function from childhood to adulthood in Turner syndrome.

BACKGROUND: Turner syndrome (TS) is a chromosomal disorder with various complications, including congenital anomaly of the kidney and urinary tract (CAKUT). However, its renal function remains poorly known. Therefore, this study aimed to evaluate renal function in TS of various ages from childhood to adulthood. METHODS: We retrospectively analyzed 63 patients with TS who visited our hospital between 1989 and 2020, examined their renal morphology, and analyzed renal function by calculating the estimated glomerular filtration rate (eGFR) using formulas applicable for Japanese populations. RESULTS: Renal morphological abnormality was observed in 22 cases (35.0%) (horseshoe kidney, 7 [11.1%]; hydronephrosis, 11 [17.5%]; duplex collecting system, 3 [4.8%]; and single unilateral kidney, 1 [1.6%]). We evaluated the eGFR of 47 subjects aged 2.8-39.3 years and classified them into Group 1 (with CAKUT, n = 15) and Group 2 (without CAKUT, n = 32). The eGFR at the first visit and the final follow-up was not statistically different between these groups. In Group 1 with CAKUT, the eGFR was not significantly different between that at the first visit and that at the final follow-up (p = 0.21). During the observation period (median, 7.9 years), the eGFR of all individuals in both groups gradually decreased with age, but did not fall < 60 mL/min/1.73 m2, which defines chronic kidney disease (CKD). CONCLUSIONS: The renal function of TS remained normal in all cases during our investigation period, and no one developed CKD by the age of 40 years.

Immunohistochemistry or Molecular Analysis: Which Method Is Better for Subtyping Craniopharyngioma?

Craniopharyngioma (CP) is mainly classified into two pathological subtypes: adamantinomatous (ACP) and papillary (PCP). CTNNB1 (ß-catenin) mutations are detected in ACPs, and the BRAF V600E mutation is detected in PCPs. However, genetic analysis is not always possible in general medical practice. In this study, we investigated whether immunohistochemistry could replace genetic analysis as an aid in subtype diagnosis. Here, 38 CP patients who had undergone their first tumor resection were included. Among the 38 cases, 22 were morphologically diagnosed as ACP, 10 cases were diagnosed as PCP, and six cases were diagnosed as undetermined CP that were morphologically difficult to classify as either ACP or PCP. Results of immunohistochemistry and genetic analysis and clinical features were compared. Based on the immunohistochemistry, 26 (22 ACPs and four undetermined CPs) showed nuclear ß-catenin expression, 11 (nine PCPs and two undetermined CPs) exhibited positive BRAF V600E immunostaining, and one PCP showed membranous ß-catenin expression and negative BRAF V600E immunostaining. Among the 26 nuclear ß-catenin expression cases, 11 had CTNNB1 mutations; however, 15 cases had mutations of neither CTNNB1 nor BRAF V600E. All 11 BRAF V600E immunopositive cases had BRAF V600E mutations. When comparing clinical features, pediatric patients and those with tumor calcification and less solid components on MRI more commonly had nuclear ß-catenin expression tumors than BRAF V600E immunopositive tumors, reflecting the differences in clinical features between ACP and PCP. Accordingly, immunohistochemistry can replace genetic analysis as an aid to determine the subtype diagnosis of CP in general medical practice.

Exploring the factors underlying remyelination arrest by studying the post-transcriptional regulatory mechanisms of cystatin F gene.

Remyelination plays an important role in determining the fate of demyelinating disorders. However, it is arrested during chronic disease states. Cystatin F, a papain-like lysosomal cysteine proteinase inhibitor, is a crucial regulator of demyelination and remyelination. Using hemizygous proteolipid protein transgenic 4e (PLP4e/- ) mice, an animal model of chronic demyelination, we found that cystatin F mRNA expression was induced at 2.5 months of age and up-regulated in the early phase of demyelination, but significantly decreased in the chronic phase. We next investigated cystatin F regulatory factors as potential mechanisms of remyelination arrest in chronic demyelinating disorders. We used the CysF-STOP-tetO::Iba-mtTA mouse model, in which cystatin F gene expression is driven by the tetracycline operator. Interestingly, we found that forced cystatin F mRNA over-expression was eventually decreased. Our findings show that cystatin F expression is modulated post-transcriptionally. We next identified embryonic lethal, abnormal vision, drosophila like RNA-binding protein 1 (ELAVL-1), and miR29a as cystatin F mRNA stabilizing and destabilizing factors, respectively. These roles were confirmed in vitro in NIH3T3 cells. Using postmortem plaque samples from human multiple sclerosis patients, we also confirmed that ELAVL-1 expression was highly correlated with the previously reported expression pattern of cystatin F. These data indicate the important roles of ELAVL-1 and miR29a in regulating cystatin F expression. Furthermore, they provide new insights into potential therapeutic targets for demyelinating disorders.

Characteristic terahertz absorption spectra of paramylon and paramylon-ester compounds.

Paramylon is a long-chain polysaccharide, composed of glucose units connected via ß-(1,3) glycosidic bonds, that spontaneously forms a three-strand helical bundle. Paramylon-esters can be made by partially or fully replacing saccharide chain hydroxide groups with carboxylic functional groups, such as stearoyl (CH3(CH2)16CO) and palmitoyl (CH3(CH2)24CO). The paramylon-ester with carboxylic acids has superior characteristics, including high thermal resistance, stability and transparency under visible light, which are necessary for thermoplastic applications. In this study, the absorption coefficient α(ν) and absorbance spectra of paramylons and paramylon-esters were measured in the 0.3-8.0 THz range and compared with the corresponding spectra of glucose and cellulose. Paramylon and paramylon-ester molecules were found to exhibit unique, so-called fingerprint, α(ν)peaks at 4.0, 6.0 and 8.0 THz, and 2.5 and 5.0 THz, respectively. We speculate that the spectral features observed are owing to intermolecular interaction modes of the weakly coupled polysaccharide chains. The paramylons with different molecular weights show very similar absorption features in the low-frequency side, both in spectral shapes and intensities, indicating that absorption is independent of molecular size. The paramylon-esters with varying degrees of substitution (DS) are similar spectral shapes but different intensities. A linear correlation between α(ν) peak intensity and the DS of paramylon-esters was established with the R2 value above 0.99. This behavior can be used for the detection and identification of novel paramylon-ester molecules.

GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma.

Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.