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Collision tumors involving the metastasis of malignant neoplasms to pituitary neuroendocrine tumors (PitNETs) are extremely rare. We herein report a case involving a patient with lung adenocarcinoma metastasis within a PitNET who exhibited relatively rapid progression of neurological symptoms. A 75-year-old man who underwent tumor resection 36 and 18 years prior to presentation for bladder and colon cancer, respectively, without recurrence presented with bitemporal hemianopsia, ptosis, and diplopia of the right eye. Subsequent magnetic resonance imaging (MRI) revealed a tumor 3.2 cm in diameter that extended from the anterior pituitary gland to the suprasellar region. Gadolinium-enhanced MRI of the tumor showed heterogeneous contrast enhancement. Considering the relatively rapid progression of neurological symptoms, semi-emergency endoscopic endonasal transsphenoidal surgery was performed. Histopathological examination revealed a group of thyroid transcription factor-1- and napsin A-positive papillary proliferating cells intermingled with α-subunit- and steroidogenic factor-1-positive PitNET cells. Thus, the patient was diagnosed with lung adenocarcinoma metastasis within a gonadotroph PitNET. Genetic testing revealed the presence of an EGFR (Ex-19del) mutation, after which chemotherapy was initiated. Additional stereotactic radiotherapy was performed for the residual tumor in the sella turcica. With continued chemotherapy, good control of both the primary and metastatic tumors was noted after 24 months after surgery. Cases of malignant neoplasm metastasis within a PitNET are difficult to diagnose. In the case of a sella turcica tumor with relatively rapid progression of neurological symptoms, early surgical intervention is recommended given the possibility of a highly proliferative tumor and the need to obtain pathologic specimens.

Abstract Background Spinal cord untethering by sectioning the filum terminale is commonly performed in tethered cord syndrome patients with minor abnormalities such as filar lipoma, thickened filum terminale, and low conus medullaris. Our endoscopic surgical technique, using the interlaminar approach, allows for sectioning the filum terminale through a very small skin incision. To our knowledge, this procedure has not been previously reported. This is the first case report involving a 1 cm skin incision. Case presentation A 9-month-old male patient was referred to our neurosurgical department due to a coccygeal dimple. MRI revealed a thickened fatty filum. After considering the treatment options for this patient, the parents agreed to spinal cord untethering. A midline 1 cm skin incision was made at the L4/5 vertebral level. Untethering by sectioning the filum terminale was performed by full endoscopic surgery using the interlaminar approach. The procedure was uneventful and there were no postoperative complications. Conclusions In terms of visibility and minimizing invasiveness, our surgical technique of using the interlaminar approach with endoscopy allows for untethering by sectioning the filum terminale through a very small skin incision.

In SuperKEKB, movable collimators reduce the beam background noise in the Belle II particle detector and protect crucial machine components, such as final focusing superconducting quadrupole magnets (QCS), from abnormal beam losses. The challenges related to the collimator, which were not properly considered at the time of SuperKEKB design, have surfaced through experience with its operation. In this paper, we report the collimator operation strategy in SuperKEKB. In addition, a significant challenge of beam collimation due to the future increase in the beam background is highlighted. We also discuss another issue caused by unexpected and sudden beam losses in the machine that damage collimators, leading to weaker beam collimation performance and an increase in transverse impedance. Furthermore, we introduce a novel collimation approach called the nonlinear collimator (NLC) to address these challenges. We detail the concept of NLC and evaluate their effectiveness by assessing the collimator impedance, beam background reduction, and impact on the dynamic aperture. The possibility of using NLCs as absorber collimators to counteract events that damage the collimator is also shown to be helpful.

Internal carotid artery (ICA) ligation for placing a high-flow extracranial-intracranial (EC-IC) bypass is used in patients with aneurysms on the cavernous portion of the ICA. Recanalization and rupture after proximal ICA ligation can occur. We present four patients who underwent endovascular distal ICA occlusion and report our surgical technique and treatment results. We ligated the ICA to place an EC-IC bypass using a radial artery (RA) graft. Failure to obtain spontaneous occlusion in the distal region required endovascular treatment an average of 219 days later. A guide catheter was placed in the common carotid artery, a guide or distal access catheter was introduced in the RA graft from the external carotid artery, and a microcatheter was navigated into the cavernous aneurysm through the RA graft. Using detachable coils, endovascular ICA occlusion was from just distal to the aneurysmal neck to a site proximal to the origin of the ophthalmic artery. Aneurysmal occlusion was completed by endovascular occlusion of the distal ICA. Complications were RA graft stenosis and transient consciousness disturbance due to local subarachnoid hemorrhage. Outpatient follow-up for a mean of 109.5 months revealed no recurrences. Distal occlusion of the ICA through the implanted RA graft is simple and presents a low risk for cerebral infarction due to thrombus formation during the procedure. To treat cavernous carotid aneurysms that do not disappear after placing the EC-IC bypass after ICA ligation at the aneurysmal neck, we offer our procedure as a treatment option.

Transarticular screw fixation is a method for posterior cervical fixation. It is ergonomic because neither connectors nor rods are needed. Biomechanical studies have shown that its fixation force is not inferior to that of lateral mass screws. More information is needed on the surgical outcome of procedures using bioabsorptive screws. We investigated the long-term surgical and radiological outcomes of posterior cervical decompression and fusion using bioabsorptive screws for transarticular fixation. Of 10 patients who underwent cervical spine transarticular fixation using bioabsorptive screws, nine presented with cervical degenerative spondylosis and one with a traumatic cervical spine injury. The mean postoperative follow-up period was 57.1 months. Transarticular screw fixation was successful in all 10 patients; no intraoperative complications were encountered. Bilateral screw breakage was discovered in a patient with cervical spine instability and associated dystonia due to cerebral palsy; there was no symptom deterioration, facet joint breakage, or instability exacerbation. Facet fusion was obtained in the nine other patients. At the patients' last visit, their clinical symptoms were significantly improved. Whole cervical spine alignment (−4.21 ± 7.2 to −5.2 ± 8.7) and the fused segment angle (mean, −0.1 ± 9.9 to −1.2 ± 13.7) did not significantly worsen postoperatively (mean: −0.1 ± 9.9 to −1.2 ± 13.7). Transarticular fixation using bioabsorptive screws is safe and associated with good long-term outcomes. In patients with exacerbation of local instability after posterior decompression, additional transarticular fixation using bioabsorbable screws is a treatment option.

Abstract Background Some patients develop immunoglobulin G4 (IgG4)-related hypophysitis associated with systemic diseases. More than 30 cases of IgG4-related hypophysitis have been reported. However, biopsy has rarely been performed in these patients, and none have had an associated pituitary neuroendocrine tumor (PitNET). We present a case of concurrent IgG4-related hypophysitis and PitNET. Case presentation A 56-year-old Japanese man arrived at the hospital with visual impairment, bitemporal hemianopia, and right abducens nerve palsy. Magnetic resonance imaging revealed pituitary body and stalk swelling as well as a small poorly enhanced right anterior lobe mass. Laboratory and loading test results suggested hypopituitarism. Because IgG4 level was elevated, a systemic examination was performed; multiple nodules were found in both lung fields. The diagnosis was based on an endoscopic transnasal biopsy of the pituitary gland. A histopathological examination revealed a marked infiltration of plasma cells into the pituitary gland, which was strongly positive for IgG4. The histological features of the resected tumor were consistent with those of gonadotroph PitNET, which was immunohistochemically positive for follicle-stimulating hormone-β and steroidogenic factor-1, and no plasma cell infiltration was observed. Based on the histopathological examination results, steroid therapy was initiated, which reduced pituitary gland size and serum IgG4 levels. Discussion and Conclusions This is the first reported case of IgG4-related hypophysitis with PitNET. Although no pathological findings indicating a relationship between the two conditions were found, we were able to preoperatively differentiate multiple lesions via detailed diagnostic imaging.

Abstract Training kits for laparoscopes for deep suturing under endoscopes are commercially available; however, previously reported training kits for endoscopic transnasal transsphenoidal pituitary/skull base surgery (eTSS) were not available in the market. Moreover, the previously reported low cost, self-made kit has the drawback of being unrealistic. This study aimed to create a low cost training kit for eTSS dura mater suturing that was as close to real as possible. Most necessary items were obtained from the 100-yen store ($1 store) or from everyday supplies. As an alternative to the endoscope, a stick-type camera was used. Through the assembly of the materials, a simple and easy-to-use training kit was created, which is almost identical to the actual dural suturing situation. In eTSS, a simple and easy-to-use training kit for dural suturing was successfully created at a low cost. This kit is expected to be used for deep suture operations and the development of surgical instruments for training.

We compared the treatment satisfaction of patients who had undergone surgery for tarsal tunnel syndrome (TTS) and carpal tunnel syndrome (CTS). We enrolled 44 patients in this study; 23 were operated for CTS and 21 for TTS. All patients had received surgery under a microscope and under local anesthesia. Using the numerical rating scale (NRS) for numbness/pain (range 0-10) we compared their preoperative outcome expectations with their satisfaction with our treatment 6 months after the operation. We also recorded their pre- and postoperative EuroQol 5-dimension 5-level (EQ-5D-5L) scale for their health-related quality of life (QOL). The subjective assessment of their QOL showed that it was significantly lower in TTS- than CTS patients both pre- and postoperatively. Six months after the operation, the NRS for symptoms and the (EQ-5D-5L) scale for the QOL were significantly improved in TTS- and CTS patients; however, these scores were significantly better after CTS- than TTS surgery. Also, the postoperative NRS was significantly lower in the CTS- than the TTS patients. Our comparison of the patients' expected- and actual surgical outcome showed that the result was better than expected after CTS- and TTS surgery; in CTS patients the difference was significant. Overall, CTS- were more satisfied than TTS patients with the treatment outcome. Satisfaction with the treatment was greater after CTS- than TTS surgery. TTS- experienced less symptom relief than CTS patients although the actual- exceeded the expected outcome in patients operated for TTS.

Mechanical thrombectomy (MT) is the standard treatment for acute large occlusion of the cerebral artery. Evidence for the success of this procedure was based on the treatment of patients with internal carotid artery and middle cerebral artery thrombi. There are a few reports on thrombi extending to the common carotid artery (CCA). We document our endovascular procedure and the clinical outcome in seven consecutive patients who underwent MT for CCA thrombi between September 2016 and April 2021. Their mean National Institutes of Health Stroke Scale score was 20.0 (range, 9-30), and the mean diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score on magnetic resonance images was 8.7 (range, 7-10). In six patients, MT of the CCA occlusion was successful, and the mean puncture-to-reperfusion time was 84 minutes (range, 39-211 minutes). In five patients, successful reperfusion was obtained. The mean total pass number was 4.1 (range, 2-7). Due to large thrombi, we performed balloon guide catheter (BGC) occlusion in three patients. Sheath occlusion occurred in two, and thrombus migration into the femoral artery around the sheath was observed in two patients. The mean modified Rankin Scale score 3 months post-stroke was 3.6 (range, 2-5). When the removal of a large CCA thrombus is attempted in a single step, catheter and sheath occlusion may occur, and this increases the risk for critical systemic artery occlusion. Therefore, we suggest that MT be combined with the BGC technique and propose the use of a large aspiration catheter to decrease the volume of the thrombus.

Indocyanine green (ICG) is a cyanine dye useful for visualizing blood vessels; it has been developed for endoscopy and is used in skull base surgery. Endoscopy is widely used for hematoma removal after an intracerebral hemorrhage since it is minimally invasive and has a shorter operation time than craniotomy. However, with this technique the surgical field is limited and it is difficult to obtain an adequate orientation; thus, it is challenging to locate the bleeding point, and postoperative rebleeding has been reported. We performed intraoperative ICG near-infrared fluorescence imaging to locate the bleeding point. This purpose of this study was to evaluate the usefulness of ICG angiography during endoscopic hematoma removal in two patients, using two endoscope types and comparing their visualization of perforating branches during the procedure. ICG angiography was performed in two different cases of putaminal hemorrhage, using the SPIES NIR/ICG-System and IMAGE1 S Rubina (both KARL STORZ, Tuttlingen, Germany) at the intraoperative bleeding site. The intraoperative use of ICG allowed the clear visualization of the perforating branches and real-time confirmation of active bleeding. We could also distinguish an old hematoma from the active bleeding point. The IMAGE1 S Rubina has adequate brightness for contrast enhancement, allowing surgical manipulation simultaneously to the enhancement phase. ICG fluorescence angiography is useful to identify the damaged vessel and perform hemostasis. We expect other similar devices to be developed in the future, accompanied by flexible and thin rigid endoscopes.

Coagulopathy, a common complication of traumatic brain injury (TBI), is characterized by a hypercoagulable state developing immediately after injury, with hyperfibrinolysis and bleeding tendency peaking 3 h after injury, followed by fibrinolysis shutdown. Reflecting this timeframe, the coagulation factor fibrinogen is first consumed and then degraded after TBI, its concentration rapidly decreasing by 3 h post-TBI. The fibrinolytic marker D-dimer reaches its maximum concentration at the same time. Hyperfibrinolysis in the acute phase of TBI is associated with poor prognosis via hematoma expansion. In the acute phase, the coagulation and fibrinolysis parameters must be monitored to determine the treatment strategy. The combination of D-dimer plasma level at admission and the level of consciousness upon arrival at the hospital can be used to predict the patients who will “talk and deteriorate.” Fibrinogen and D-dimer levels should determine case selection and the amount of fresh frozen plasma required for transfusion. Surgery around 3 h after injury, when fibrinolysis and bleeding diathesis peak, should be avoided if possible. In recent years, attempts have been made to estimate the time of injury from the time course of coagulation and fibrinolysis parameter levels, which has been particularly useful in some cases of pediatric abusive head trauma patients.

Tarsal tunnel syndrome (TTS) is a common entrapment syndrome whose diagnosis can be difficult. We compared preoperative magnetic resonance imaging (MRI) and operative findings in 23 consecutive TTS patients (28 sides) whose mean age was 74.5 years. The 1.5T MRI sequence was 3D T2* fat suppression. We compared the MRI findings with surgical records and intraoperative videos to evaluate them. MRI- and surgical findings revealed that a ganglion was involved on one side (3.6%), and the other 27 sides were diagnosed with idiopathic TTS. MRI visualized the nerve compression point on 23 sides (82.1%) but failed to reveal details required for surgical planning. During surgery of the other five sides (17.9%), three involved varices, and on one side each, there was connective tissue entrapment or nerve compression due to small vascular branch strangulation. MRI studies were useful for nerve compression due to a mass lesion or idiopathic factors. Although MRI revealed the compression site, it failed to identify the specific involvement of varices and small vessel branches and the presence of connective tissue entrapment.

Crystal violet (CV) ink has been used as a skin marker worldwide. It has been reported to be useful for vessel wall visualization of microvascular anastomoses. Contrastingly, it has been found to be carcinogenic and inhibit migration and proliferation of venous cells. In some countries, its use in the medical field has been restricted. Therefore, it is necessary to consider alternatives to CV. In this present study, we compared the time required for the anastomosis of a 0.8-1 mm diameter vessel in the chicken wrist artery using CV and a CV-free dye (ethyl violet; EV). The surgeon, microscope, and anastomosis microsurgical tools were standardized for comparison. CV and EV were changed for each anastomosis. The same surgeon performed 30 anastomoses using each dye. No visually obvious differences were noted in the vascular transections with CV and EV. As per the results, no statistically significant difference was observed in the time required for anastomosis using CV and EV. EV conforming to California Proposition 65 may be an effective alternative to CV for vascular visualization of microvascular anastomoses. However, further studies on the effectiveness of the EV in clinical cases are needed.

Background: Endoscopic transsphenoidal surgery (ETSS) is performed more frequently in elderly patients. We investigated endocrinological pitfalls in pituitary surgery in the elderly by a comparative study focusing only on elderly patients. Methods: Ninety-nine elderly patients aged 65 years and over with non-functioning pituitary adenoma (NFPA) who underwent ETSS were retrospectively examined and classified into the early (aged 65–74 years) and late (aged 75 years and over) elderly groups. The baseline characteristics and anterior pituitary function were compared between the groups. Results: Seventy patients were assigned to the early elderly group and 29 to the late elderly group. Thyroid-stimulating hormone (TSH) response in preoperative and postoperative thyrotropin-releasing hormone (TRH) tests revealed a significant difference between the groups. Preoperative and postoperative TSH responses were significantly correlated in both groups. Residual analysis of the correlation between preoperative free triiodothyronine (T3) secretion quantity and preoperative TSH response in both groups, which was significant, indicated that preoperative TSH response was significantly normal when preoperative free T3 secretion quantity was normal in the early elderly group, but preoperative free T3 secretion quantity was significantly lower regardless of preoperative TSH response in the late elderly group. Conculsions: The present study suggested that preoperative and postoperative TSH secretory capacity was presumed to be normal when preoperative free T3 levels were normal in the early elderly patients with NFPA. On the other hand, TSH secretory capacity in the late elderly patients could only be assessed by the TRH test, which should be taken into account.

Coagulopathy is a common sequela of traumatic brain injury. Consumptive coagulopathy and secondary hyperfibrinolysis are associated with hypercoagulability. In addition, fibrinolytic pathways are hyperactivated as a result of vascular endothelial cell damage in the injured brain. Coagulation and fibrinolytic parameters change dynamically to reflect these pathologies. Fibrinogen is consumed and degraded after injury, with fibrinogen concentrations at their lowest 3-6 h after injury. Hypercoagulability causes increased fibrinolytic activity, and plasma levels of D-dimer increase immediately after traumatic brain injury, reaching a maximum at 3 h. Owing to disseminated intravascular coagulation in the presence of fibrinolysis, the bleeding tendency is highest within the first 3 h after injury, and often a condition called “talk and deteriorate” occurs. In neurointensive care, it is necessary to measure coagulation and fibrinolytic parameters such as fibrinogen and D-dimer routinely to predict and prevent the development of coagulopathy and its negative outcomes. Currently, the only evidence-based treatment for traumatic brain injury with coagulopathy is tranexamic acid in the subset of patients with mild-to-moderate traumatic brain injury. Coagulation and fibrinolytic parameters should be closely monitored, and treatment should be considered on a patient-by-patient basis.

Abstract The ring finger protein 213 (RNF213) susceptibility gene has been detected in more than 80% of Japanese and Korean patients with moyamoya disease (MMD), a bilateral internal carotid artery (ICA) occlusion. Furthermore, RNF213 has been detected in more than 20% of East Asians with atherosclerotic ICA stenosis. In this study, we evaluated the frequency of RNF213 mutations in congenital occlusive lesions of the ICA system. This case series was conducted jointly at four university hospitals. Patients with a family history of MMD, quasi-MMD, or related diseases were excluded. Ten patients were diagnosed with abnormal ICA or middle cerebral artery (MCA) angiogenesis. Patients with neurofibromatosis were excluded. Finally, nine patients with congenital vascular abnormalities were selected; of these, five had ICA deficiency and four had twig-like MCA. The RNF213 c.14576G > A mutation was absent in all patients. Therefore, the RNF213 c.14576G > A mutation may not be associated with ICA and MCA congenital dysplasia—rare vascular anomalies making it difficult to study a large number of cases. However, an accumulation of cases is required for accurate determination. The results of this study may help differentiate congenital vascular diseases from MMD.

Abstract Background Sepsis is often associated with multiple organ failure; however, changes in brain volume with sepsis are not well understood. We assessed brain atrophy in the acute phase of sepsis using brain computed tomography (CT) scans, and their findings’ relationship to risk factors and outcomes. Methods Patients with sepsis admitted to an intensive care unit (ICU) and who underwent at least two head CT scans during hospitalization were included (n = 48). The first brain CT scan was routinely performed on admission, and the second and further brain CT scans were obtained whenever prolonged disturbance of consciousness or abnormal neurological findings were observed. Brain volume was estimated using an automatic segmentation method and any changes in brain volume between the two scans were recorded. Patients with a brain volume change

Study Design Retrospective study. Purpose This study aims to evaluate the effectiveness of mirogabalin in treatment of peripheral neuropathic pain due to lumbar spine disease. Overview of Literature Mirogabalin is a novel selective ligand for the α2δ subunit of voltage-gated Ca channels. Methods Between April and December 2019, we used mirogabalin to treat 60 consecutive patients (mean age, 67.6 years) with leg symptoms due to lumbar disease. The treatment outcome after 8 weeks of mirogabalin therapy was evaluated by comparing the preand post-administration Numerical Rating Scale (NRS) for leg symptoms and sleep disturbance, the NRS and Roland–Morris Disability Questionnaire for low back pain (LBP), and the quality of life (QOL) score (based on EuroQol five-dimension five-level scale). Results Mirogabalin treatment was stopped at less than eight weeks in eight patients. The remaining 52 patients for evaluation were divided as group 1 (17 patients who presented with leg symptoms that lasted for less than 3 months) and group 2 (35 patients with leg symptoms that lasted longer than 3 months). The leg symptoms and LBP in both groups significantly improved at 4 and 8 weeks of treatment, and sleep disturbance and QOL were improved at 8 weeks as well. Compared to group 2, the pretreatment leg symptoms and QOL were significantly worse in group 1, and their improvement after 8 weeks of mirogabalin treatment was significantly better (p

Abstract Spectroscopic sensing provides physical and chemical information in a non-destructive and rapid manner. To develop non-destructive estimation methods of tea quality-related metabolites in fresh leaves, we estimated the contents of free amino acids, catechins, and caffeine in fresh tea leaves using visible to short-wave infrared hyperspectral reflectance data and machine learning algorithms. We acquired these data from approximately 200 new leaves with various status and then constructed the regression model in the combination of six spectral patterns with pre-processing and five algorithms. In most phenotypes, the combination of de-trending pre-processing and Cubist algorithms was robustly selected as the best combination in each round over 100 repetitions that were evaluated based on the ratio of performance to deviation (RPD) values. The mean RPD values were ranged from 1.1 to 2.7 and most of them were above the acceptable or accurate threshold (RPD = 1.4 or 2.0, respectively). Data-based sensitivity analysis identified the important hyperspectral regions around 1500 and 2000 nm. Present spectroscopic approaches indicate that most tea quality-related metabolites can be estimated non-destructively, and pre-processing techniques help to improve its accuracy.

Neurofibromatosis type 2 (NF2) causes bilateral vestibular schwannomas (VSs), leading to deafness. VS is treated by surgery or radiation, but neither treatments prevent hearing loss. Bevacizumab was found to be effective in suppressing the tumor’s growth and may help to improve hearing. We are conducting a randomized, double-blind, multicenter clinical trial to verify the efficacy and safety of bevacizumab in NF2-related VS. The primary objective is to evaluate the efficacy of bevacizumab in improving hearing in the affected ear. One of the secondary objectives is to evaluate bevacizumab’s efficacy in rechallenge treatment in relapsed cases. Sixty patients will randomly receive either bevacizumab or a placebo and will be clinically observed for 48 weeks in the initial intervention phase. In the first half (24 weeks), they will receive either 5 mg/kg of bevacizumab or a placebo drug. In the second half, all patients will receive 5 mg/kg of bevacizumab. If hearing function deteriorated in a patient who had shown improvement during the first phase, a rechallenge dose with bevacizumab would be offered.

BackgroundInjury to the internal carotid artery (ICA) during endoscopic transsphenoidal surgery (ETSS) is a serious complication with a risk of mortality. ICA injury during ETSS usually occurs during intrasellar manipulations and rarely occurs in the extrasellar portion. Several hemostatic procedures have been proposed for ICA injury in the intrasellar portion, whereas hemostatic methods for ICA injury in the extrasellar portion, where the ICA is surrounded by bone structures, are less well known.Case PresentationA 65-year-old man with an incidental pituitary tumor underwent ETSS. The petrous portion of the left ICA was injured during resection of the sphenoid septum connected with left carotid prominence using a cutting forceps. Bleeding was too heavy for simple hemostatic techniques. Hemostasis using a crushed muscle patch was tried unsuccessfully during controlling of the bleeding. Eventually, the injured site of the ICA was covered with cotton patties followed by closing with a vascularized pedicled nasoseptal flap. Cerebral angiography immediately after surgery showed no extravasation from the injured site of the left ICA petrous portion. However, a carotid-cavernous sinus fistula originating from the injured ICA site was detected 7 days after surgery, so the vascular reconstructive surgery combined with left ICA occlusion was performed. The overall postoperative course was uneventful.ConclusionWe believe that emergency application of the cottonoids may be effective for hemostasis against ICA injury in the extrasellar portion during ETSS, but further vascular reconstruction combined with ICA occlusion on the injured side and removal of the cottonoids would be required.

Abstract Effectively using genomic information greatly accelerates conventional breeding and applying it to long-lived crops promotes the conversion to genomic breeding. Because tea plants are bred using conventional methods, we evaluated the potential of genomic predictions (GPs) and genome-wide association studies (GWASs) for the genetic breeding of tea quality-related metabolites using genome-wide single nucleotide polymorphisms (SNPs) detected from restriction site-associated DNA sequencing of 150 tea accessions. The present GP, based on genome-wide SNPs, and six models produced moderate prediction accuracy values (r) for the levels of most catechins, represented by ( −)-epigallocatechin gallate (r = 0.32–0.41) and caffeine (r = 0.44–0.51), but low r values for free amino acids and chlorophylls. Integrated analysis of GWAS and GP detected potential candidate genes for each metabolite using 80–160 top-ranked SNPs that resulted in the maximum cumulative prediction value. Applying GPs and GWASs to tea accession traits will contribute to genomics-assisted tea breeding.

To the best of our knowledge, we report a case of MEN2A complicated by moyamoya syndrome. A 52-year-old woman presented with vertigo. Magnetic resonance angiography (MRA) revealed bilateral supraclinoid stenosis of the internal carotid artery and abnormal moyamoya-like vessels around the basal ganglia. She had a heterozygous variant of RNF213, which is the susceptibility gene for moyamoya disease. She had also previously received diagnoses of medullary thyroid carcinoma (MTC) at age 23 and left-sided pheochromocytoma (PHEO) at age 41. Genetic testing revealed heterozygosity for a mutation at codon 634 in exon 11 (TGC-TTC mutation; p.Cys634Phe) of the Ret gene. Intracranial vascular stenosis may have been caused by a genetic mutation of RNF213 and hypersecretion of catecholamines by MEN2A. Physicians should recognize that MEN2A can be present with moyamoya syndrome.

Introduction: Kidney impairment appears to be more common after Carotid artery stenting (CAS) than after carotid endarterectomy (CEA), although few data are available on the CEArelated risk. Therefore, we assessed kidney function in the perioperative CEA period. We also describe our new method for creating useful images without contrast media and an intraoperative CEA technique for preventing renal impairment. Methods: Our study included 244 patients undergoing CEA. We assessed the estimated glomerular filtration rate (eGFR) in the perioperative period, and the endpoint was renal function impairment (RFI: eGFR of more than 20 mL/min/1.73 m2 from the first measurement of eGFR). For patients with prohibited contrast media, we constructed images from computed tomography of the neck and magnetic resonance angiography without contrast media and used an operative technique with a surgical microscope to treat plaques in a high location. Results: The eGFR in the 122 patients undergoing CEA (54.0%) was

Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus−associated systemic angiocentric and angiodestructive lymphoproliferative disorder. It commonly involves the lungs and can also affect the skin, liver, kidney, and central nervous system. It can rarely occur in the spine, however, the details are unclear. We performed a systematic review of published cases (including our 1 case) of spinal LYG.We performed a systematic search of studies in English on spinal LYG, focusing on its clinical features, imaging, and treatments, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on the PubMed database. We identified 14 patients from the literature. We also found 1 case of isolated cervical LYG (grade 3) who was treated with steroid and radiation therapy for the spinal lesion after pathologic diagnosis. We performed a pooled analysis of these 15 cases.The mean age was 43.4 years, and 13 of the 15 patients were male. Brain lesions were present in 11 of 12 intramedullary spinal lesions, and only 1 was an isolated spinal LYG case. Regarding the diagnostic methods, 1 case was not described. Of the 14 cases described, 12 patients underwent biopsies (7 brain, 4 lung, and 1 spinal cord lesion) and 2 underwent surgical removal for an extramedullary lesion. In the overall prognosis from a mean follow-up period of 21.6 months, 4 patients died despite several treatments.Spinal LYG, particularly isolated spinal LYG, is rare. Thus further accumulation of cases may be necessary to better understand its characteristics.

Background and Purpose Prediction of intracranial aneurysm growth risk can assist physicians in planning of follow-up imaging of conservatively managed unruptured intracranial aneurysms. We therefore aimed to externally validate the ELAPSS (Earlier subarachnoid hemorrhage, aneurysm Location, Age, Population, aneurysm Size and Shape) score for prediction of the risk of unruptured intracranial aneurysm growth. Methods From 11 international cohorts of patients ≥18 years with ≥1 unruptured intracranial aneurysm and ≥6 months of radiological follow-up, we collected data on the predictors of the ELAPSS score, and calculated 3- and 5-year absolute growth risks according to the score. Model performance was assessed in terms of calibration (predicted versus observed risk) and discrimination (c-statistic). Results We included 1,072 patients with a total of 1,452 aneurysms. During 4,268 aneurysm-years of follow-up, 199 (14%) aneurysms enlarged. Calibration was comparable to that of the development cohort with the overall observed risks within the range of the expected risks. The c-statistic was 0.69 (95% confidence interval [CI], 0.64 to 0.73) at 3 years, compared to 0.72 (95% CI, 0.68 to 0.76) in the development cohort. At 5 years, the c-statistic was 0.68 (95% CI, 0.64 to 0.72), compared to 0.72 (95% CI, 0.68 to 0.75) in the development cohort. Conclusions The ELAPSS score showed accurate calibration for 3- and 5-year risks of aneurysm growth and modest discrimination in our external validation cohort. This indicates that the score is externally valid and could assist patients and physicians in predicting growth of unruptured intracranial aneurysms and plan follow-up imaging accordingly.

Abstract Intracranial aneurysm (IA) is a socially important disease as a major cause of subarachnoid hemorrhage. Recent experimental studies mainly using animal models have revealed a crucial role of macrophage-mediated chronic inflammatory responses in its pathogenesis. However, as findings from comprehensive analysis of unruptured human IAs are limited, factors regulating progression and rupture of IAs in humans remain unclear. Using surgically dissected human unruptured IA lesions and control arterial walls, gene expression profiles were obtained by RNA sequence analysis. RNA sequencing analysis was done with read count about 60~100 million which yielded 6~10 billion bases per sample. 79 over-expressed and 329 under-expressed genes in IA lesions were identified. Through Gene Ontology analysis, ‘chemokine activity’, ‘defense response’ and ‘extracellular region’ were picked up as over-represented terms which included CCL3 and CCL4 in common. Among these genes, quantitative RT-PCR analysis using another set of samples reproduced the above result. Finally, increase of CCL3 protein compared with that in control arterial walls was clarified in IA lesions. Findings of the present study again highlight importance of macrophage recruitment via CCL3 in the pathogenesis of IA progression.

Several metabolites define tea quality in new tea shoots composed of leaf and stem. To improve tea quality for breeding, it is important to understand the tissue-dependent genetic mechanisms and metabolic network responsible for the profile of tea quality-related metabolites. We analyzed the volatiles and specialized metabolites as the tea quality-related metabolites in leaves and stems of new shoots in 30 tea accessions to understand the tissue variation and network between tea quality-related metabolites. Our results provided the tissue-dependent variation network in the tea quality-related metabolites, including volatiles in new leaves and stems in tea accessions. Each volatile content in tea accessions showed the coefficient of variation ranging from 58.7 to 221.9% and 54.2 to 318.3% in new leaves and new stems, respectively. The accumulation pattern of tea quality-related metabolites in new leaves and stems varied depending on the accession. When comparing tea genetic populations, the profile of tea quality-related metabolites of new leaves, but not new stems, was the key to distinguishing tea genetic populations by chemical indicators. We described the network between tea quality-related metabolites, especially the dense network in new leaves. These results also will provide the key information for metabolic engineering and the selection of breeding materials in tea plants based on the tea quality-related metabolites and aid in understanding their molecular mechanisms and network of metabolic variation.

Plant albinism causes the etiolation of leaves because of factors such as deficiency of chloroplasts or chlorophylls. In general, albino tea leaves accumulate higher free amino acid (FAA) contents than do conventional green tea leaves. To explore the metabolic changes of etiolated leaves (EL) in the light-sensitive Japanese albino tea cultivar “Koganemidori,” we performed integrated metabolome and transcriptome analyses by comparing EL with green leaves induced by bud-sport mutation (BM) or shading treatments (S-EL). Comparative omics analyses indicated that etiolation-induced molecular responses were independent of the light environment and were largely influenced by the etiolation itself. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and pathway analyses revealed the downregulation of genes involved in chloroplast development and chlorophyll biosynthesis and upregulation of protein degradation-related pathways, such as the ubiquitin-proteasome system and autophagy in EL. Metabolome analysis showed that most quantified FAAs in EL were highly accumulated compared with those in BM and S-EL. Genes involved in the tricarboxylic acid (TCA) cycle, nitrogen assimilation, and the urea cycle, including the drastically downregulated Arginase-1 homolog, which functions in nitrogen excretion for recycling, showed lower expression levels in EL. The high FAA contents in EL might result from the increased FAA pool and nitrogen source contributed by protein degradation, low N consumption, and stagnation of the urea cycle rather than through enhanced amino acid biosynthesis.

Expression profiles of gonadal steroid receptor variants have been reportedly associated with malignancy in breast and prostate cancers [1,2]. However, such associations with pituitary tumors remain unclear. Therefore, the expression levels of the wild-type ESR1 (ERα66) and the ESR1 variants (ERαi34, ERαi45c, and ERαΔ5) transcripts encoding constitutively active ERα proteins with C-terminal truncation in non-functioning pituitary adenomas (NFPAs) were evaluated using reverse transcription-digital polymerase chain reaction. The results revealed that the expression levels of the variants were approximately two orders of magnitude lower than that of ERα66 in NFPAs. These data were based on our previous article entitled “Accurate assessment of estrogen receptor profiles in non-functioning pituitary adenomas using RT-digital PCR and immunohistochemistry” [3].

Orbital emphysema after nose-blowing is an uncommon condition and can appear without a trigger. Herein, we reported a case of orbital emphysema after nose-blowing and performed a literature review. A 68-year-old man fell and sustained an injury near his left orbit. No symptoms were noted. He noticed a left periorbital swelling after blowing his nose. Through computed tomography examination, he was diagnosed with subcutaneous emphysema. There are no previous reports that have reviewed the clinical features, need for surgery, and severity of symptoms of subcutaneous emphysema after nasal swallowing due to different factors. We retrospectively analyzed a cohort of 48 cases by searching PubMed to clarify these issues. Regarding the emphysema trigger, 21 cases had an injury or had previously undergone surgery. In 34 cases, conservative treatment was required, while surgery was selected in the acute phase in 6 cases and after the acute phase as a radical cure in 8 cases. Reduced visual acuity, diplopia, exophthalmos, facial hypoesthesia, and color disorders were noted and were more common among surgical cases. The literature review revealed no association between fracture location and the need for surgery; furthermore, surgery was less required in non-trauma cases, excluding osteoma, than in trauma cases (p = 0.0169). Our study reveals that a strict follow-up examination of visual symptoms is necessary for the first 2 days in cases of subcutaneous emphysema caused by nose blowing after facial trauma.

Leaf chlorophyll content is used as a major indicator of plant stress and growth, and hyperspectral remote sensing is frequently used to monitor the chlorophyll content. Hyperspectral reflectance has been used to evaluate vegetation properties such as pigment content, plant structure and physiological features using portable spectroradiometers. However, the prices of these devices have not yet decreased to consumer-affordable levels, which prevents widespread use. In this study, a system based on a cost-effective fingertip-sized spectrometer (Colorcompass-LF, a total price for the proposed solution was approximately 1600 USD) was evaluated for its ability to estimate the chlorophyll contents of radish and wasabi leaves and was compared with the Analytical Spectral Devices FieldSpec4. The chlorophyll contents per leaf area (cm2) of radish were generally higher than those of wasabi and ranged from 42.20 to 94.39 μg/cm2 and 11.39 to 40.40 μg/cm2 for radish and wasabi, respectively. The chlorophyll content was estimated using regression models based on a one-dimensional convolutional neural network (1D-CNN) that was generated after the original reflectance from the spectrometer measurements was de-noised. The results from an independent validation dataset confirmed the good performance of the Colorcompass-LF after spectral correction using a second-degree polynomial, and very similar estimation accuracies were obtained for the measurements from the FieldSpec4. The coefficients of determination of the regression models based on 1D-CNN were almost same (with R2 = 0.94) and the ratios of performance to deviation based on reflectance after spectral correction using a second-degree polynomial for the Colorcompass-LF and the FieldSpec4 were 4.31 and 4.33, respectively.

Shade cultivation is a traditional Japanese tea cultivation method in which the shoot buds are shaded for several weeks. This technique is increasingly used for green tea production because it produces tea of high quality (as indicated by umami and nutritional content) and commands high prices. However, given that shaded tea plants are grown under low-light stress, concerns exist regarding damage to tea plants caused by repeated shade cultivation. To understand basic physiological responses and accumulative changes in photosynthetic ability and metabolites of tea plants subjected to repeated shading, we performed a pot experiment on immature tea plants grown in a growth chamber subjected to repeated shading treatments. The results demonstrated that shade cultivation caused a decrease in non-structural carbohydrate content and an increase of several degrees in leaf surface temperature, reflecting transpiration through the leaf stomata, as a result of a reduction in photosynthetic ability. An increase of several degrees in canopy temperature and a reduction in photosynthetic ability in the field in the mid-summer season was also observed in overstressed tea plants subjected to repeated shading. Metabolomic analysis identified several candidate biomarkers, such as citrulline and glycine betaine, that were significantly changed in individuals affected by shade cultivation. These physiological changes may be an indicator of the stress status of tea plants grown under repeated shade cultivation.

Lipomas of the cerebellopontine angle (CPA) and internal auditory canal (IAC) are relatively rare tumors. Acoustic neurinoma is the most common tumor in this location, which often causes hearing loss, vertigo, and tinnitus. Occasionally, this tumor compresses the brainstem, prompting surgical resection. Lipomas in this area may cause symptoms similar to neurinoma. However, they are not considered for surgical treatment because their removal may result in several additional deficits. Conservative therapy and repeated magnetic resonance imaging examinations for CPA/IAC lipomas are standard measures for preserving cranial nerve function. Herein, we report a case of acoustic neurinoma and CPA lipoma occurring in close proximity to each other ipsilaterally. The main symptom was hearing loss without facial nerve paralysis. Therefore, facial nerve injury had to be avoided. Considering the anatomical relationships among the tumors, cranial nerves, and CPA/IAC lipoma, we performed total surgical removal of the acoustic neurinoma. We intentionally left the lipoma untreated, which enabled facial nerve preservation. This report may be a useful reference for the differential diagnosis of similar cases in the future.

Spinal epidural hematoma (SEDH) without pain due to epidural anesthesia is a rare but serious complication. We report the successful treatment of a patient with progressive paraparesis after the development of SEDH during the administration of epidural anesthesia. An 84-year-old woman underwent laparoscopy with epidural anesthesia. To prevent deep vein thrombosis, the delivery of low molecular weight heparin was started 16.5 hours after laparoscopy. On the 1st postoperative day she reported painless leg paralysis and on the 2nd day she manifested severe paraplegia and urinary retention. Magnetic resonance imaging revealed an SEDH compressing the spinal cord at the Th12 - L1 and we performed emergent laminectomy. After the laminectomy her symptoms disappeared completely. SEDH is a rare but serious complication related to epidural anesthesia. As its excessive analgesic effect may elicit motor weakness and mask pain, SEDH must be ruled out in patients with paraparesis with continuous epidural anesthesia.

The stress-reducing effect of matcha, a high-quality fine-powdered green tea, has recently been clarified by animal experiments and clinical trials. However, the effect of matcha added to confectioneries is not clear. One aim of this study was to evaluate the relationship between matcha components and their stress-reducing effect in mice that were loaded with territorially-based stress. Adrenal hypertrophy, a marker of stress, was significantly suppressed in stress-loaded mice that had ingested matcha components, displaying a caffeine and epigallocatechin gallate to theanine and arginine (CE/TA) ratio of 2 or less. Another aim was to evaluate, in humans, the stress-reducing effect of matcha in cookies using test-matcha (CE/TA = 1.79) or placebo-matcha (CE/TA = 10.64). Participants, who were fifth year pharmacy college students, consumed 4.5 g of matcha in three pieces of cookie daily for 15 days. Salivary α-amylase activity, a stress marker, was significantly lower in the test-matcha group than in the placebo group. These results indicate that the CE/TA ratio of tea components is a key indicator for the suppression of stress. Moreover, matcha with a CE/TA ratio of 2 or less displays a stress-reducing effect, even if it is included in confectionery products. Such products may also benefit individuals who have no habit of drinking matcha as a beverage.

To obtain genetic information about the germplasm of tea (Camellia sinensis L.) in Japan, 167 accessions including 138 var. sinensis (96 Japanese var. sinensis and 42 exotic var. sinensis) and 29 Assam hybrids were analyzed using single nucleotide polymorphisms (SNPs) markers identified by double-digest restriction-site-associated DNA sequencing (ddRAD-seq) analysis. Approximately 10,000 SNPs were identified by ddRAD-seq and were mapped across the whole genome. The 167 tea accessions were classified into three genetic subgroups: (1) Japanese var. sinensis; (2) Japanese and exotic var. sinensis; (3) Assam hybrids and exotic var. sinensis. Leaf morphology varied widely within each genetic subgroups. The 96 Japanese var. sinensis were classified into four genetic subgroups as follows; two subgroups of Shizuoka (the largest tea production region) landraces, Uji (most ancient tea production region) landraces, and the pedigree of 'Yabukita', the leading green tea cultivar in Japan. These results indicated that the SNP markers obtained from ddRAD-seq are a useful tool to investigate the geographical background and breeding history of Japanese tea. This genetic information revealed the ancestral admixture situation of the 'Yabukita' pedigree, and showed that the genome structure of 'Yabukita' is clearly different from those of other Japanese accessions.

Japanese horseradish (wasabi) grows in very specific conditions, and recent environmental climate changes have damaged wasabi production. In addition, the optimal culture methods are not well known, and it is becoming increasingly difficult for incipient farmers to cultivate it. Chlorophyll a, b and carotenoid contents, as well as their allocation, could be an adequate indicator in evaluating its production and environmental stress; thus, developing an in situ method to monitor photosynthetic pigments based on reflectance could be useful for agricultural management. Besides original reflectance (OR), five pre-processing techniques, namely, first derivative reflectance (FDR), continuum-removed (CR), de-trending (DT), multiplicative scatter correction (MSC), and standard normal variate transformation (SNV), were compared to assess the accuracy of the estimation. Furthermore, five machine learning algorithms—random forest (RF), support vector machine (SVM), kernel-based extreme learning machine (KELM), Cubist, and Stochastic Gradient Boosting (SGB)—were considered. To classify the samples under different pH or sulphur ion concentration conditions, the end of the red edge bands was effective for OR, FDR, DT, MSC, and SNV, while a green-peak band was effective for CR. Overall, KELM and Cubist showed high performance and incorporating pre-processing techniques was effective for obtaining estimated values with high accuracy. The best combinations were found to be DT–KELM for chl a (RPD = 1.511–5.17, RMSE = 1.23–3.62 μg cm−2) and chl a:b (RPD = 0.73–3.17, RMSE = 0.13–0.60); CR–KELM for chl b (RPD = 1.92–5.06, RMSE = 0.41–1.03 μg cm−2) and chl a:car (RPD = 1.31–3.23, RMSE = 0.26–0.50); SNV–Cubist for car (RPD = 1.63–3.32, RMSE = 0.31–1.89 μg cm−2); and DT–Cubist for chl:car (RPD = 1.53–3.96, RMSE = 0.27–0.74).

Endogenous nicotine was confirmed to be present in tea plants (Camellia sinensis L.) by liquid chromatography-tandem mass spectrometry of tea samples from tea-producing regions in six Asian countries. All samples contained nicotine (0.011-0.694 μg g-1 dry weight). Nicotine contents remained constant during manufacturing of green, oolong and black teas, implying that nicotine is stable against heating, drying, enzymatic oxidation and mechanical damage during processing. Flower buds and seeds of cultivar Yabukita also contained nicotine (0.030-0.041 μg g-1 dry weight). A comparison of two cultivars revealed that higher nicotine contents were found in the black tea cultivar Benifuki. All plant parts of hydroponic Yabukita contained nicotine (0.003-0.013 μg g-1 dry weight). Tea cells cultured in B5 medium as well as roots and stems of tea seedlings contained nicotine levels similar to those of new leaves from field-grown plants. Although the levels of endogenous nicotine in tea plants are extremely low and sample contamination cannot be discounted, these levels exceed the maximum acceptable limit in Japan (0.01 μg g-1 dry weight).

Gremlin is an antagonist of bone morphogenetic protein (BMP) and a major driving force in skeletal modeling in the fetal stage. Several recent reports have shown that Gremlin is also involved in angiogenesis of lung cancer and diabetic retinopathy. The purpose of this study was to investigate the role of Gremlin in tumor angiogenesis in pituitary adenoma. Double fluorescence immunohistochemistry of Gremlin and CD34 was performed in pituitary adenoma tissues obtained during transsphenoidal surgery in 45 cases (7 PRLoma, 17 GHoma, 2 ACTHoma, and 2 TSHoma). Gremlin and microvascular density (MVD) were detected by double-immunofluorescence microscopy in CD34-positive vessels from tissue microarray analysis of 60 cases of pituitary adenomas (6 PRLoma, 23 GHoma, 22 NFoma, 5 ACTHoma, and 4 TSHoma). In tissue microarray analysis, MVD was significantly correlated with an increased Gremlin level (linear regression: P

Modern colliders bring into collision a large number of bunches to achieve a high luminosity. The long-range beam-beam effects arising from parasitic encounters at such colliders are mitigated by introducing a crossing angle. Under these conditions, crab cavities (CC) can be used to restore effective head-on collisions and thereby to increase the geometric luminosity. Such crab cavities have been proposed for both linear and circular colliders. The crab cavities are rf cavities operated in a transverse dipole mode, which imparts on the beam particles a transverse kick that varies with the longitudinal position along the bunch. The use of crab cavities in the Large Hadron Collider (LHC) may not only raise the luminosity, but it could also complicate the beam dynamics, e.g., crab cavities might not only cancel synchrobetatron resonances excited by the crossing angle but they could also excite new ones, they could reduce the dynamic aperture for off-momentum particles, they could influence the aperture and orbit, also degrade the collimation cleaning efficiency, and so on. In this paper, we explore the principal feasibility of LHC crab cavities from a beam dynamics point of view. The implications of the crab cavities for the LHC optics, analytical and numerical luminosity studies, dynamic aperture, aperture and beta beating, emittance growth, beam-beam tune shift, long-range collisions, and synchrobetatron resonances, crab dispersion, and collimation efficiency will be discussed.

Optics correction is an important issue in the KEKB B-factory. Especially, the correction of beta functions is performed so as to reach near half-integer resonance of the horizontal betatron tune as closely as possible. Consequently, the luminosity can be improved during experiments of the B-meson in e^{+}e^{-} collisions. Therefore, we have developed a correction method of the beta function not only at the designed beam energy, but also at an energy deviated from the nominal value. We present the procedures used to measure the behavior of the beta function, which depends on the momentum deviation, and the results compared with the model optics in the KEKB rings.

A compact proton synchrotron using combined function magnets is proposed to help realize the wider availability of charged particle cancer therapy facilities. This combined function magnet was designed with the help of three-dimensional magnetic field calculations to take account of a realistic fringe and the interference among the magnetic poles. An evaluation scheme for tune values based on particle tracking was developed to improve the magnet design. To verify the magnet design, a model magnet was fabricated and measured. In order to achieve a tune value evaluation from the measured magnetic field, schemes for accurate field mapping and field interpolation were developed. From the tune value evaluation of the measured magnetic field, it was thought that the performance of the model magnet was good enough to construct a synchrotron. In this paper, we report details of the design and the evaluation scheme for the combined function magnet and the results of the field measurements of the model magnet.