Thyroid metastasis of p16-positive OPSCC

Thyroid metastasis is rarely diagnosed, and the treatment outcomes in p16-positive oropharyngeal squamous cell carcinoma patients with rare thyroid metastasis have not been fully investigated. Here we describe the case of a patient with p16-positive oropharyngeal squamous cell carcinoma who was diagnosed with cT4 N2M1 with rare thyroid metastasis. The patient was a current smoker and was positive for human papillomavirus DNA, with disease progression at 49 days and death at 113 days after completion of cisplatin-based concurrent chemoradiotherapy

Phylogenetic position of a whale-fall lancelet (Cephalochordata) inferred from whole mitochondrial genome sequences

<p>Abstract</p> <p>Background</p> <p>The lancelet <it>Asymmetron inferum </it>(subphylum Cephalochordata) was recently discovered on the ocean floor off the southwest coast of Japan at a depth of 229 m, in an anaerobic and sulfide-rich environment caused by decomposing bodies of the sperm whale <it>Physeter macrocephalus</it>. This deep sulfide-rich habitat of <it>A. inferum </it>is unique among the lancelets. The distinguishing adaptation of this species to such an extraordinary habitat can be considered in a phylogenetic framework. As the first step of reconstruction of the evolutionary processes in this species, we investigated its phylogenetic position based on 11 whole mitochondrial genome sequences including the newly determined ones of the whale-fall lancelet <it>A. inferum </it>and two coral-reef congeners.</p> <p>Results</p> <p>Our phylogenetic analyses showed that extant lancelets are clustered into two major clades, the <it>Asymmetron </it>clade and the <it>Epigonichthys </it>+ <it>Branchiostoma </it>clade. <it>A. inferum </it>was in the former and placed in the sister group to <it>A. lucayanum </it>complex. The divergence time between <it>A. inferum </it>and <it>A. lucayanum </it>complex was estimated to be 115 Mya using the penalized likelihood (PL) method or 97 Mya using the nonparametric rate smoothing (NPRS) method (the middle Cretaceous). These are far older than the first appearance of large whales (the middle Eocene, 40 Mya). We also discovered that <it>A. inferum </it>mitogenome (mitochondrial genome) has been subjected to large-scale gene rearrangements, one feature of rearrangements being unique among the lancelets and two features shared with <it>A. lucayanum </it>complex.</p> <p>Conclusion</p> <p>Our study supports the monophyly of genus <it>Asymmetron </it>assumed on the basis of the morphological characters. Furthermore, the features of the <it>A. inferum </it>mitogenome expand our knowledge of variation within cephalochordate mitogenomes, adding a new case of transposition and inversion of the <it>trnQ </it>gene. Our divergence time estimation suggests that <it>A. inferum </it>remained a member of the Mesozoic and the early Cenozoic large vertebrate-fall communities before shifting to become a whale-fall specialist.</p

Generation of a Mutant Mucor hiemalis Endoglycosidase That Acts on Core-fucosylated N-Glycans

Endo-β-N-acetylglucosaminidase M (Endo-M), an endoglycosidase from the fungus Mucor hiemalis, is a useful tool for chemoenzymatic synthesis of glycoconjugates, including glycoprotein-based therapeutics having a precisely defined glycoform, by virtue of its transglycosylation activity. Although Endo-M has been known to act on various N-glycans, it does not act on core-fucosylated N-glycans, which exist widely in mammalian glycoproteins, thus limiting its application. Therefore, we performed site-directed mutagenesis on Endo-M to isolate mutant enzymes that are able to act on mammalian-type core-α1,6-fucosylated glycans. Among the Endo-M mutant enzymes generated, those in which the tryptophan at position 251 was substituted with alanine or asparagine showed altered substrate specificities. Such mutant enzymes exhibited increased hydrolysis of a synthetic α1,6-fucosylated trimannosyl core structure, whereas their activity on the afucosylated form decreased. In addition, among the Trp-251 mutants, the W251N mutant was most efficient in hydrolyzing the core-fucosylated substrate. W251N mutants could act on the immunoglobulin G-derived core-fucosylated glycopeptides and human lactoferrin glycoproteins. This mutant was also capable of transferring the sialyl glycan from an activated substrate intermediate (sialyl glyco-oxazoline) onto an α1,6-fucosyl-N-acetylglucosaminyl biotin. Furthermore, the W251N mutant gained a glycosynthase-like activity when a N175Q substitution was introduced and it caused accumulation of the transglycosylation products. These findings not only give insights into the substrate recognition mechanism of glycoside hydrolase family 85 enzymes but also widen their scope of application in preparing homogeneous glycoforms of core-fucosylated glycoproteins for the production of potent glycoprotein-based therapeutics

Direct Brachial Approach for Acute Basilar Artery Occlusion: Technical Note and Preliminary Clinical Experience

In mechanical endovascular thrombectomy (MET) for acute basilar artery occlusion (ABAO) in the elderly, navigating a guide catheter via the femoral artery may be difficult due to the approach route’s significant tortuosity. To resolve this problem, we have been performing a technique that uses a direct brachial approach (DiBA) with a large-bore aspiration catheter. We reported our preliminary clinical experience with this technique. MET for ABAO using the DiBA technique was performed on 4 consecutive patients between August 2017 and December 2018. In all patients, thrombolysis in cerebral infarction 2B or 3 recanalization was achieved, but the modified Rankin Scale at 90 days was ≥4. There were no technical difficulties or complications with this technique. The DiBA technique is an effective and feasible approach in MET for ABAO. Although excellent clinical outcomes could not be achieved, the angiographic outcomes were excellent with no technical complications. This approach can be an alternative to the femoral artery approach, particularly for tortuous arteries in the elderly

Characterization of an active LINE-1 in the naked mole-rat genome.

Naked mole-rats (NMRs, Heterocephalus glaber) are the longest-living rodent species. A reason for their long lifespan is pronounced cancer resistance. Therefore, researchers believe that NMRs have unknown secrets of cancer resistance and seek to find them. Here, to reveal the secrets, we noticed a retrotransposon, long interspersed nuclear element 1 (L1). L1s can amplify themselves and are considered endogenous oncogenic mutagens. Since the NMR genome contains fewer L1-derived sequences than other mammalian genomes, we reasoned that the retrotransposition activity of L1s in the NMR genome is lower than those in other mammalian genomes. In this study, we successfully cloned an intact L1 from the NMR genome and named it NMR-L1. An L1 retrotransposition assay using the NMR-L1 reporter revealed that NMR-L1 was active retrotransposon, but its activity was lower than that of human and mouse L1s. Despite lower retrotrasposition activity, NMR-L1 was still capable of inducing cell senescence, a tumor-protective system. NMR-L1 required the 3' untranslated region (UTR) for retrotransposition, suggesting that NMR-L1 is a stringent-type of L1. We also confirmed the 5' UTR promoter activity of NMR-L1. Finally, we identified the G-quadruplex structure of the 3' UTR, which modulated the retrotransposition activity of NMR-L1. Taken together, the data indicate that NMR-L1 retrotranspose less efficiently, which may contribute to the cancer resistance of NMRs

Obstetric pelvimetry by three-dimensional computed tomography in non-pregnant Japanese women: a retrospective single-center study

OBJECTIVE: While a basic understanding of pelvic size and typology is still important for obstetricians, pelvic measurement data for Japanese women are very scarce. To our best knowledge, no large-scale pelvimetry studies of Japanese women have been made for the past 50 years. This study aimed to investigate the accurate size, particularly the obstetric conjugate (OC) and transverse diameter of the pelvic inlet (TD), of modern Japanese women, using three-dimensional (3D) computed tomography (CT), and to obtain their reference values. METHODS: This retrospective, single-center observational study enrolled Japanese non-pregnant women aged between 20 and 40 years, who underwent pelvic CT examination from 2016 to 2021. CT was performed for various reasons, including acute abdomen, search for cancer metastases, and follow-up of existing disease. However, no cases were taken for pelvic measurements. Pelvimetry was performed retrospectively using a 3D workstation. The OC was measured on a strict lateral view and the TD was measured on an axial-oblique view. Other clinical data, such as age, height, and weight, were also extracted from the medical charts and analyzed. RESULTS: A total of 1, 263 patients were enrolled, with the mean age of 32.7 years (standard deviation [SD] 6.2). The mean height, weight, and body mass index were 158.8 cm (SD 5.8), 54.8 kg (SD 11.7), and 21.7 kg/m2 (SD 4.4), respectively. The mean OC length was 127.0 mm (SD 9.5, 95% confidence interval [CI] 126.5-127.5), while the mean TD length was 126.8 mm (SD 7.5, 95% CI 126.4-127.2). Both values were normally distributed. Height was significantly associated with OC (regression coefficient = 0.75 [95% CI 0.66-0.84], p < .001) and TD (regression coefficient = 0.63 [95% CI 0.56-0.70], p < .001). Age showed a weak but statistically significant positive association with TD (regression coefficient = 0.14 [95% CI 0.07-0.20], p < .001) and OC (regression coefficient = -0.10 [95% CI -0.18 to -0.01], p = .026). CONCLUSION: The 3D CT pelvimetry in 1, 263 non-pregnant Japanese women of childbearing age revealed the mean OC and TD of 127.0 mm, and 126.8 mm, which were 11.8 mm and 4.3 mm larger, respectively, than those in the survey in 1972. Our data will be referred to in clinical practice as the standard pelvic measurement values for the Japanese population

Optimal Number of Systematic Biopsy Cores Used in Magnetic Resonance Imaging/Transrectal Ultrasound Fusion Targeted Prostate Biopsy

[Background] In recent years, the effectiveness of magnetic resonance imaging (MRI)-ultrasound fusion targeted biopsy (MRF-TB) has been widely reported. In this study, we assessed the effect of reduction of the number of systematic biopsy (SB) cores on the cancer detection rate (CDR). [Methods] Patients with a high prostate-specific antigen (PSA) level underwent prostate MRI. The Prostate Imaging-Reporting and Data System version 2 (PI-RADS) was then used to rate the lesions. The inclusion criteria were as follows: (1) PSA level between 4.0 and 30.0 ng/mL and (2) patients with one or more lesions on MRI and a PI-RADS score of 3 or more. All enrolled patients were SB naïve or had a history of one or more prior negative SBs. A total of 104 Japanese met this selection criterion. We have traditionally performed 14-core SB following the MRF-TB. In this study, the CDRs of 10-core SB methods, excluding biopsy results at the center of the base and mid-level on both sides, were compared with those of the conventional biopsy method. [Results] We compared CDRs of the 14-core and 10-core SBs used in combination. The overall CDR was 55.8% for the former and 55.8% for the latter, thereby indicating that there was no significant difference (P = 1.00) between the two. In addition, the CDRs of csPCa were 51.9% for the former and 51.1% for the latter, which indicated that there was no significant difference (P = 0.317). [Conclusion] There was no significant difference in the CDR when the number of SB cores to be used in combination was 14 and 10