Effects of high-frequency hyperthermia on the elastic modulus of the lumbar muscle in female athletes with low back pain: A randomized crossover trial.

OBJECTIVE: To investigate the effects of capacitive and resistive monopolar radiofrequency (CRMF) on the shear elastic modulus of the multifidus and erector spinae muscles in female athletes with low back pain (LBP) and a history of LBP. DESIGN: Randomized crossover trial. SETTING: Academic institution. PARTICIPANTS: Twenty female university athletes with LBP or a history of LBP were included. INTERVENTIONS: All participants received CRMF, hotpack, and sham (CRMF without power) in a random order on the right side of the lumbar region. More than 2 days were allocated between the experiments to eliminate any residual effects. MAIN OUTCOME MEASURES: The shear elastic moduli of the right multifidus and erector spinae were evaluated in the prone (rest) position while sitting with 35° trunk flexion (stretched) using shear wave ultrasound imaging equipment. The moduli were measured before, immediately after, and 30 minutes after the intervention. RESULTS: Repeated-measures 2-way analysis of variance and post hoc analysis showed that the moduli of the CRMF group were significantly lower than those of the sham group in the stretched position immediately after intervention (P = .045). This difference diminished 30 minutes after the intervention (P = .920). CONCLUSIONS: CRMF can be used to reduce the shear elastic modulus of the multifidus muscle in the short term. Further studies are warranted to determine how to provide longer effects. TRIAL REGISTRATION: None.

Clinical, imaging, and molecular features of radiation-induced glioblastomas developing more than 20 years after radiation therapy for intracranial germinomatous germ cell tumor: illustrative cases.

BACKGROUND: Germinomatous germ cell tumor is highly sensitive to chemoradiotherapy; patients are expected to survive for decades. Many radiation-induced malignant gliomas (RIMGs) occur >10 years after radiotherapy. Standard therapy for RIMGs has not been established because of the lesion's rarity, the patient's shorter survival period, and the risk of radiation necrosis by repeat radiation. OBSERVATIONS: Two patients, a 32-year-old man and a 50-year-old man, developed glioblastomas more than 20 years after radiation monotherapy for germinoma with or without mature teratoma. The first patient showed a tumor in the left frontotemporal region with disseminated lesions and died 2 months after partial resection of the tumor without responding to the chemotherapy with temozolomide and bevacizumab. Methylation classifier analysis classified the pathology as closest to diffuse pediatric-type high-grade glioma, Rtk1 subtype. The second patient showed a tumor mass in the brainstem and left cerebellar peduncle, which worsened progressively during chemotherapy with temozolomide and bevacizumab. The tumor transiently responded to stereotactic radiotherapy with the CyberKnife. However, the patient died of RIMG recurrence-related aspiration pneumonia 11 months after the biopsy. Methylation classifier analysis classified the pathology as closest to infratentorial pilocytic astrocytoma. LESSONS: Chemoradiotherapy may improve the survival of patients with RIMGs. Furthermore, molecular features may influence the clinical, locoregional, and pathological features of RIMG.

Machine Learning-Based Rapid Post-Earthquake Damage Detection of RC Resisting-Moment Frame Buildings.

This study proposes a methodology to predict the damage condition of Reinforced Concrete (RC) resisting-moment frame buildings using Machine Learning (ML) methods. Structural members of six hundred RC buildings with varying stories and spans in X and Y directions were designed using the virtual work method. Sixty thousand time-history analyses using ten spectrum-matched earthquake records and ten scaling factors were carried out to cover the structures' elastic and inelastic behavior. The buildings and earthquake records were split randomly into training data and testing data to predict the damage condition of new ones. In order to reduce bias, the random selection of buildings and earthquake records was carried out several times, and the mean and standard deviation of the accuracy were obtained. Moreover, 27 Intensity Measures (IM) based on acceleration, velocity, or displacement from the ground and roof sensor responses were used to capture the building's behavior features. The ML methods used IMs, the number of stories, and the number of spans in X and Y directions as input data and the maximum inter-story drift ratio as output data. Finally, seven Machine Learning (ML) methods were trained to predict the damage condition of buildings, finding the best set of training buildings, IMs, and ML methods for the highest prediction accuracy.

Differences in the elastic modulus of the lumbar muscles between female athletes with and without low back pain.

BACKGROUND: Low back pain is the most prevalent musculoskeletal disorder affecting performance and sports participation among athletes and is more prevalent among female athletes. Evaluating the stiffness of the lumbar muscles is important for understanding the pathophysiology of low back pain. Therefore, this study examined the differences in stiffness of the lumbar multifidus and erector spinae muscles between female university athletes with and without low back pain. METHODS: This was a cross-sectional study. The study was conducted at a single centre, the university research laboratory. Twenty female university athletes with low back pain or a history of low back pain and 20 without low back pain participated in this study. The shear elastic moduli of the multifidus and erector spinae muscles were evaluated in the prone (to relax the muscles) and sitting with 35° of trunk flexion (to stretch the muscles) positions using shear wave ultrasound imaging equipment. FINDINGS: The low back pain group showed significantly greater shear elastic modulus in the multifidus in both prone and sitting positions than the non-low back pain group. There were no differences in the erector spinae muscle between the two groups at either position. INTERPRETATION: These results provide new insights into the microscopic characteristics of low back pain pathophysiology in young female athletes. Stiffness assessment using shear wave elastography will help provide a specific treatment strategy for female athletes with low back pain or a history of low back pain.

Preoperative three-dimensional multifusion imaging aiding successful microvascular decompression of a cerebellopontine angle lipoma: associated hemifacial spasm. Illustrative case.

BACKGROUND: Cerebellopontine angle (CPA) lipoma-associated hemifacial spasm (HFS) is rare. As the removal of CPA lipomas has a high risk of worsening the neurological symptoms, surgical exploration is warranted only in selected patients. Preoperative identification of the lipoma affected site of the facial nerve, and offending artery are crucial for patient selection and successful microvascular decompression (MVD). OBSERVATIONS: Presurgical simulation using three-dimensional (3D) multifusion imaging showed a tiny CPA lipoma wedged between the facial and auditory nerves, as well as an affected facial nerve by the anterior inferior cerebellar artery (AICA) at the cisternal segment. Although a recurrent perforating artery from the AICA anchored the AICA to the lipoma, successful MVD was achieved without lipoma removal. LESSONS: The presurgical simulation using 3D multifusion imaging could identify the CPA lipoma, affected site of the facial nerve, and offending artery. It was helpful for patient selection and successful MVD.

Epigenetic upregulation of Schlafen11 renders WNT- and SHH-activated medulloblastomas sensitive to cisplatin.

BACKGROUND: Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma. METHODS: SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo. RESULTS: High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells. CONCLUSIONS: High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.

Meningoencephalocele in the Lateral Sphenoid Sinus Showing Malformation of Cortical Development: A Case Report.

Meningoencephalocele in the lateral sphenoid sinus (SS) has been determined to be a rare entity often detected by cerebrospinal fluid (CSF) rhinorrhea. To date, the pathology of meningoencephalocele in the lateral SS has remained to be unclear in many cases. In this study, we report on a case of a 72-year-old woman with an arteriovenous malformation who presented with CSF rhinorrhea. Radiologic investigations revealed a left temporal meningoencephalocele in the lateral SS. We removed the meningoencephalocele and performed skull base repair, after which the CSF rhinorrhea resolved. Pathological examination showed congenital cortical abnormalities with dysmorphic neurons in various shapes and acquired chronic tissue alterations including fibrillary gliosis and scattered Rosenthal fibers. These findings may further aid in understanding the etiopathogenesis of meningoencephalocele in the lateral SS.

Successful Treatment of Acute Uric Acid Nephropathy with Rasburicase in a Primary Central Nervous System Lymphoma Patient Showing a Dramatic Response to Methotrexate-Case Report.

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are sensitive to chemotherapy. The standard treatment is high-dose methotrexate (MTX)-based chemotherapy. There are no reports of successful treatment of acute uric acid nephropathy with rasburicase after MTX administration in PCNSLs. CASE PRESENTATION: A 54-year-old man with a history of gout presented with a change in character and cognitive dysfunction. MRI showed a large enhancing mass spanning the bilateral frontal lobes and the right temporal lobe. After endoscopic biopsy, an MTX, procarbazine, and vincristine (MPV) regimen was initiated for the treatment of the PCNSL. After the initiation of chemotherapy, the patient experienced a gout attack, and blood examination revealed acute renal failure (ARF) and hyperuricemia. The considered causes of ARF included MTX toxicity and acute uric acid nephropathy. As the dramatic effect of MTX was observed, treatment was continued despite ARF, most probably due to acute hyperuricemia due to tumor lysis, which was treated in parallel. After an improvement in renal function, MTX was resumed, and rasburicase was initiated to control hyperuricemia. A complete response was obtained after induction chemotherapy. Hyperuricemia was controlled with rasburicase, and renal function was preserved. CONCLUSIONS: Acute uric acid nephropathy should be considered when ARF occurs after the initiation of MTX in PCNSLs, especially in newly diagnosed PCNSL patients with large tumors or hyperuricemia.

High-Performance Liquid Chromatography Mapping Method for the Structural Analysis of N-Glycans at the Molecular, Cellular, and Tissue Levels.

Glycans on viruses are major molecules that mediate the communication of the viruses with host cells. Investigating the structure of glycans may be important in the characterization of viruses. In this regard, the high-performance liquid chromatography (HPLC) is a widely used analytical technique. We developed a multidimensional HPLC mapping method that identifies glycan structures. This is achieved by separating and purifying glycans using three types of HPLC columns and comparing the elution time data with known data. This method enables the easy profiling of glycans at the molecular, cellular, and tissue levels and can be used to study the glycans of virological samples such as virus and their hosts. It also enables the discrimination of isomers, which is difficult via mass spectrometry. In this paper, we describe in detail the principle and method of the structural analysis of N-type glycans using the proposed method.

Convolutional Neural Network-Based Rapid Post-Earthquake Structural Damage Detection: Case Study.

It is necessary to detect the structural damage condition of essential buildings immediately after an earthquake to identify safe structures, evacuate, or resume crucial activities. For this reason, a CNN methodology proposed to detect the structural damage condition of a building is here improved and validated for two currently instrumented essential buildings (Tahara City Hall and Toyohashi Fire Station). Three-dimensional frames instead of lumped mass models are used for the buildings. Besides this, a methodology to select records is introduced to reduce the variability of the structural responses. The maximum inter-storey drift and absolute acceleration of each storey are used as damage indicators. The accuracy is evaluated by the usability of the building, total damage condition, storey damage condition, and total comparison of the damage indicators. Finally, the maximum accuracy and R2 of the responses are obtained as follows: for the Tahara City Hall building, 90.0% and 0.825, respectively; for the Toyohashi Fire Station building, 100% and 0.909, respectively.

An embeddable molecular code for Lewis X modification through interaction with fucosyltransferase 9.

N-glycans are diversified by a panel of glycosyltransferases in the Golgi, which are supposed to modify various glycoproteins in promiscuous manners, resulting in unpredictable glycosylation profiles in general. In contrast, our previous study showed that fucosyltransferase 9 (FUT9) generates Lewis X glycotopes primarily on lysosome-associated membrane protein 1 (LAMP-1) in neural stem cells. Here, we demonstrate that a contiguous 29-amino acid sequence in the N-terminal domain of LAMP-1 is responsible for promotion of the FUT9-catalyzed Lewis X modification. Interestingly, Lewis X modification was induced on erythropoietin as a model glycoprotein both in vitro and in cells, just by attaching this sequence to its C-terminus. Based on these results, we conclude that the amino acid sequence from LAMP-1 functions as a "Lewis X code", which is deciphered by FUT9, and can be embedded into other glycoproteins to evoke a Lewis X modification, opening up new possibilities for protein engineering and cell engineering.

Mechanical Thrombectomy for Bihemispheric Infarction Caused by Acute Unilateral Internal Carotid Artery Occlusion in a Patient with Contralateral Chronic Carotid Occlusion: A Case Report.

Objective: We report a patient with acute bihemispheric infarction who underwent mechanical thrombectomy. Case Presentation: A 76-year-old man suddenly developed coma and quadriplegia. Brain MRI and MRA revealed acute bihemispheric infarction due to occlusions of both the internal carotid arteries (ICAs). According to the DSA findings, we considered the left ICA as chronic occlusion and the right as acute. Mechanical thrombectomy for the right ICA occlusion was performed. Total recanalization was achieved using a stent retriever 181 minutes after onset. The left hemisphere was perfused by cross circulation through the anterior communicating artery, but the symptoms did not improve. MRI the day after thrombectomy showed extensive bihemispheric infarction. Recanalization for the bilateral hemispheres was maintained, although the left ICA remained occluded. He died 2 months later due to gastrointestinal bleeding. Conclusion: Acute bihemispheric infarction due to occlusions of both ICAs is a rare entity. The symptoms are very severe and the therapeutic time window is extremely short because of absent collateral pathways. We should consider pre-existing carotid occlusive disease, determine whether the occlusions are acute or chronic, and perform prompt therapy. Further investigation is warranted to obtain a better outcome.

Structural Response Prediction for Damage Identification Using Wavelet Spectra in Convolutional Neural Network.

If damage to a building caused by an earthquake is not detected immediately, the opportunity to decide on quick action, such as evacuating the building, is lost. For this reason, it is necessary to develop modern technologies that can quickly obtain the structural safety condition of buildings after an earthquake in order to resume economic and social activities and mitigate future damage by aftershocks. A methodology for the prediction of damage identification is proposed in this study. Using the wavelet spectrum of the absolute acceleration record measured by a single accelerometer located on the upper floor of a building as input data, a CNN model is trained to predict the damage information of the building. The maximum ductility factor, inter-story drift ratio, and maximum response acceleration of each floor are predicted as the damage information, and their accuracy is verified by comparing with the results of seismic response analysis using actual earthquakes. Finally, when an earthquake occurs, the proposed methodology enables immediate action by revealing the damage status of the building from the accelerometer observation records.

G-quadruplex-forming aptamer enhances the peroxidase activity of myoglobin against luminol.

Aptamers can control the biological functions of enzymes, thereby facilitating the development of novel biosensors. While aptamers that inhibit catalytic reactions of enzymes were found and used as signal transducers to sense target molecules in biosensors, no aptamers that amplify enzymatic activity have been identified. In this study, we report G-quadruplex (G4)-forming DNA aptamers that upregulate the peroxidase activity in myoglobin specifically for luminol. Using in vitro selection, one G4-forming aptamer that enhanced chemiluminescence from luminol by myoglobin's peroxidase activity was discovered. Through our strategy-in silico maturation, which is a genetic algorithm-aided sequence manipulation method, the enhancing activity of the aptamer was improved by introducing mutations to the aptamer sequences. The best aptamer conserved the parallel G4 property with over 300-times higher luminol chemiluminescence from peroxidase activity more than myoglobin alone at an optimal pH of 5.0. Furthermore, using hemin and hemin-binding aptamers, we demonstrated that the binding property of the G4 aptamers to heme in myoglobin might be necessary to exert the enhancing effect. Structure determination for one of the aptamers revealed a parallel-type G4 structure with propeller-like loops, which might be useful for a rational design of aptasensors utilizing the G4 aptamer-myoglobin pair.

MALDI-TOF mass spectrometry imaging for N-glycans on FFPE tissue sections of mouse NASH liver through Sialic acid Benzylamidation.

Glycans play an important physiological role and are drawing attention as biomarkers that capture pathophysiological changes. Glycans can be detected by mass spectrometry, but recently matrix-assisted laser desorption/ionization- mass spectrometry imaging (MALDI-MSI) has enabled the visualization of glycans distribution on tissues. In this study, focusing on sialylated glycan (sialoglycans), we investigated the amidation reaction used to visualize glycans distribution, and developed a method of sialic acid derivatization by benzylamidation which is more sensitive than conventional amidation. Furthermore, we adapted this method for visualizing glycans in formalin-fixed paraffin-embedded (FFPE) liver tissue from normal mice and non-alcoholic steatohepatitis (NASH) model mice using MALDI-MSI. As a result, an increase in the distribution of glycan N-Acetylneuraminic acid-(NeuAc) ions was observed in the NASH mouse liver, and the change in glycan structure in the NASH model was clarified.

Choroid Plexus Papilloma in the Fourth Ventricle Associated with Pheochromocytoma: A Case Report.

We report for the first time a case of choroid plexus papilloma (CPP) of the fourth ventricle associated with adrenal pheochromocytoma. A large tumor was found in the fourth ventricle of a 24-year-old man who presented with symptoms of increased intracranial pressure due to obstructive hydrocephalus. A systemic search revealed that the patient also had an asymptomatic left adrenal tumor. Both tumors were resected. The pathological diagnosis of the brain tumor was CPP and that of the adrenal tumor was pheochromocytoma, both of which showed no pathological signs of malignancy. Genetic testing for von Hippel-Lindau disease was negative. There have been no reports of cases of CPP associated with pheochromocytoma. In this report, we discuss the relationship between both tumors.

[Surgical Case of Accidental Infantile Acute Subdural Hematoma Caused by Household Minor Head Trauma:Hyperperfusion during Postoperative Hemispheric Hypodensity, Namely "Big Black Brain"].

We experienced a case of an accidental infantile acute subdural hematoma caused by household minor head trauma(Nakamura type I intracranial hemorrhage)with postoperative hemispheric hypodensity lesion(Big Black Brain)whose pathophysiology was analyzed using perfusion MRI. A ten-month-old boy was admitted to our hospital in a comatose state. His mother revealed that the boy suffered a fall from a sofa bed. A CT scan indicated massive acute subdural hematoma in the left cerebral hemisphere. Emergency craniotomy and hematoma evacuation were performed. On postoperative day 3, CT revealed hemispheric hypodensity, and the boy suffered from status epilepticus. MRI on the following day showed widespread white matter hyperintensity in diffusion-weighted images, and MRA demonstrated dilation of the middle cerebral artery. Perfusion MRI using the dynamic susceptibility contrast method revealed a marked increase in cerebral blood flow in the left hemisphere. These abnormal MRI and MRA findings disappeared on postoperative day 13. Status epilepticus also improved upon administration of multi-antiepileptic drugs. Fundoscopy findings on postoperative day 3 showed small bilateral petechial or brush retinal hemorrhages. However, whole-body examination did not show any problems, and was consistent with the mother's account. Thus, we judged non-abusive head trauma. Although follow-up MRI showed diffuse atrophy of the left cerebral hemisphere, the boy aged well without obvious paresis or verbal developmental delay as judged by a follow-up more than a year later. Based on these results, we speculated that hyperperfusion caused by dilation of the cerebral artery was related to the postoperative hemispheric hypodensity, namely "Big Black Brain".

Improved secretion of glycoproteins using an N-glycan-restricted passport sequence tag recognized by cargo receptor.

MCFD2 and ERGIC-53, which are the products of causative genes of combined factor V and factor VIII deficiency, form a cargo receptor complex responsible for intracellular transport of these coagulation factors in the early secretory pathway. In this study, using an NMR technique, we successfully identified an MCFD2-binding segment from factor VIII composed of a 10 amino acid sequence that enhances its secretion. This prompted us to examine possible effects of attaching this sequence to recombinant glycoproteins on their secretion. We found that the secretion level of recombinant erythropoietin was significantly increased simply by tagging it with the passport sequence. Our findings not only provide molecular basis for the intracellular trafficking of coagulation factors and their genetic deficiency but also offer a potentially useful tool for increasing the production yields of recombinant glycoproteins of biopharmaceutical interest.

EDEM2 stably disulfide-bonded to TXNDC11 catalyzes the first mannose trimming step in mammalian glycoprotein ERAD.

Sequential mannose trimming of N-glycan (Man9GlcNAc2 -> Man8GlcNAc2 -> Man7GlcNAc2) facilitates endoplasmic reticulum-associated degradation of misfolded glycoproteins (gpERAD). Our gene knockout experiments in human HCT116 cells have revealed that EDEM2 is required for the first step. However, it was previously shown that purified EDEM2 exhibited no α1,2-mannosidase activity toward Man9GlcNAc2 in vitro. Here, we found that EDEM2 was stably disulfide-bonded to TXNDC11, an endoplasmic reticulum protein containing five thioredoxin (Trx)-like domains. C558 present outside of the mannosidase homology domain of EDEM2 was linked to C692 in Trx5, which solely contains the CXXC motif in TXNDC11. This covalent bonding was essential for mannose trimming and subsequent gpERAD in HCT116 cells. Furthermore, EDEM2-TXNDC11 complex purified from transfected HCT116 cells converted Man9GlcNAc2 to Man8GlcNAc2(isomerB) in vitro. Our results establish the role of EDEM2 as an initiator of gpERAD, and represent the first clear demonstration of in vitro mannosidase activity of EDEM family proteins.

[Posterior Quadrantectomy for Infant with Refractory Epilepsy:A Case Report].

We present the case of an 11-month-old girl with linear nevus sebaceous syndrome who underwent posterior quadrantectomy(PQ)for intractable epilepsy due to cortical dysplasia extending from the temporal, parietal, and occipital lobes in the right hemisphere. Epileptic spasms started at 4 months after birth, and the frequency of her seizures gradually increased to 10 episodes per day. Electroencephalograms in the interictal periods showed hypsarrhythmia. Magnetic resonance imaging(MRI)suggested cortical dysplasia in the right temporal, parietal, and occipital lobes. Ictal single-photon emission computed tomography revealed increased cerebral blood flow in similar areas as the cortical dysplasia suggested on MRI. Several antiepileptic drugs were administered to control the epileptic spasms, without success. In addition, her developmental delay gradually became evident. Because the epileptic foci extended into the posterior region of the right hemisphere, we did not execute a focused resection, but performed a PQ. The epileptic spasms completely disappeared after surgery and her developmental delay gradually improved. Early surgical intervention via PQ is useful in patients with drug-resistant epilepsy in whom the epileptic foci have extended into the temporal, parietal, and occipital lobes. This intervention not only controls intractable seizures but also helps to facilitate normal development.