The Visualization of Intraneural Venous Compression in Trigeminal Neuralgia by Using Advanced Three-Dimensional Computer Graphics: An Illustrative Case Report.

Trigeminal neuralgia (TN) caused by venous compression presents challenges in surgical management, unlike the arterial type. Preoperative diagnostic certainty regarding venous etiology and anatomical relationships is crucial for surgical success. We discuss a case of TN caused by a vein passing through the nerve that was challenging to visualize on conventional MRI and was treated successfully by leveraging information from modern surgical simulation technology with 3D computer graphics. We recognized a potentially troublesome anatomical feature in advance and mitigated the risk by identifying a collateral drainage route for the causative vein, making it feasible to be sacrificed while ensuring treatment efficacy.

DMRT1 regulates human germline commitment.

Germline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from human embryonic stem cells in vitro. We show that switching from BMP signalling for PGC specification to Activin A and retinoic acid resulted in DMRT1 and CDH5 expression, the indicators of migratory PGCs in vivo. Moreover, the induction of DMRT1 and SOX17 in PGC-like cells promoted epigenetic resetting with striking global enrichment of 5-hydroxymethylcytosine and locus-specific loss of 5-methylcytosine at DMRT1 binding sites and the expression of DAZL representing DNA methylation-sensitive genes, a hallmark of the germline commitment programme. We provide insight into the unique role of DMRT1 in germline development for advances in human germ cell biology and in vitro gametogenesis.

The impact of SAH finding on CT to the clinical outcome after mechanical thrombectomy for large vessel occlusion.

BACKGROUND AND PURPOSE: Whether subarachnoid haemorrhage (SAH) after mechanical thrombectomy affects the clinical outcomes of patients with acute large-vessel occlusion remains unclear. This study aimed to investigate the clinical impact of SAH on computed tomography (CT) after mechanical thrombectomy. METHODS: The SKIP study was an investigator-initiated, multicentre, randomised, open-label clinical trial. This study was performed in 23 hospital networks in Japan from January 1, 2017, to July 31, 2019. Among the 204 patients, seven were excluded because they did not undergo mechanical thrombectomy (MT) and had a modified Rankin scale (mRS) score > 2. The main outcome was the association between SAH within 36 h after mechanical thrombectomy and the clinical outcome at 90 days. RESULTS: Among 197 patients, the median age was 74 (67-79) years, 62.9% were male. Moreover, 26 (13.2%) patients had SAH (seven isolated SAH) on CT within 36 h. The SAH rate did not differ according to IV rt-PA administration (p = 0.4). The rate of favourable clinical outcomes tended to be lower in patients with SAH rather than patients without SAH (11 [42%] vs. 106 [62%], p = 0.08). Among the seven patients with isolated SAH, 6 showed favourable outcomes at 90 days. In the multivariate regression analysis, the presence of SAH within 36 h from onset was not associated with clinical outcome (Odd ratio, 0.59; 95% confidence interval, 0.18-1.95; p = 0.38). CONCLUSIONS: Among patients with acute stroke treated with MT, SAH, especially isolated SAH findings on CT, were not associated with poor clinical outcomes after 90 days. TRIAL REGISTRATION NUMBER: UMIN000021488.

Ultra-early rt-PA administration should improve patient outcome on mechanical thrombectomy: Post hoc analysis of SKIP.

BACKGROUND: To investigate whether ultra-early recombinant tissue-plasminogen activator (rt-PA) administration can improve patient outcomes on mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO). METHODS: Participants comprised rt-PA-eligible 204 patients with internal carotid artery or middle cerebral artery occlusion in the SKIP trial, who were randomly assigned to receive mechanical thrombectomy alone or combined intravenous thrombolysis (rt-PA: alteplase at 0.6 mg/kg) plus mechanical thrombectomy. We assessed associations between onset-to-puncture time and onset-to-rt-PA administration time and frequency of favorable outcome at 90 days and any intracerebral hemorrhage (ICH) at 36 h after onset. RESULTS: As a cut-off onset-to-puncture time for favorable outcome, receiver operating characteristic curves defined 2.5 h (57% sensitivity, 62% specificity). For onset-to-puncture times ≤2.5 h and > 2.5 h, frequencies of favorable outcomes were 72% and 63% (p = 0.402) in patients with rt-PA therapy and 44% and 58% (p = 0.212) in patients without rt-PA therapy, respectively. In terms of onset-to-rt-PA administration time, frequencies of favorable outcomes among patients with ultra-early rt-PA administration at ≤100, >100 min after onset, and without rt-PA therapy with onset-to-puncture time ≤ 2.5 h, and with and without rt-PA therapy with onset-to-puncture time > 2.5 h were 84% and 64%, 63%, and 44% and 58%, respectively (p = 0.025). Frequencies of any ICH among those patients were 37% and 32%, 32%, and 63% and 40%, respectively (p = 0.006). CONCLUSION: Ultra-early rt-PA administration should improve patient outcomes on mechanical thrombectomy among patients with LVO. Relatively late rt-PA administration might increase the frequency of any ICH.

Modular Oxidation of Cytosine Modifications and Their Application in Direct and Quantitative Sequencing of 5-Hydroxymethylcytosine.

Selective, efficient, and controllable oxidation of cytosine modifications is valuable for epigenetic analyses, yet only limited progress has been made. Here, we present two modular chemical oxidation reactions: conversion of 5-hydroxymethylcytosine (5hmC) into 5-formylcytosine (5fC) using 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (ACT+BF4-) and further transformation of 5fC into 5-carboxycytosine (5caC) through Pinnick oxidation. Both reactions are mild and efficient on double-stranded DNA. We integrated these two oxidations with borane reduction to develop chemical-assisted pyridine borane sequencing plus (CAPS+), for direct and quantitative mapping of 5hmC. Compared with CAPS, CAPS+ improved the conversion rate and false-positive rate. We applied CAPS+ to mouse embryonic stem cells, human normal brain, and glioblastoma DNA samples and demonstrated its superior sensitivity in analyzing the hydroxymethylome.

Cerebral syphilitic Gumma in the modern era: a report of an unusual case and brief review of recent published reports.

BACKGROUND: Cerebral syphilitic gummas are rare. However, numerous case reports on them have been published recently, consistent with the resurgence of syphilis and its accompanying atypical manifestations. We here present a patient with a cerebral syphilitic gumma and an unusual clinical course and review recent case reports. CASE PRESENTATION: A 49-year-old woman had a generalised seizure and was found by computed tomography and magnetic resonance imaging to have a brain mass that mimicked a brain abscess or malignant tumour. Further imaging with magnetic resonance spectroscopy and positron emission tomography did not contribute further to the differential diagnosis. Because treatment with ceftriaxone was ineffective, the lesion was resected. Serological tests on serum and cerebrospinal fluid were positive for syphilis and histopathological examination of the operative specimen revealed a syphilitic gumma. Antibiotic treatment is preferred over invasive interventions for cerebral syphilitic gumma. However, as in our case, radical resection is required when antibiotic treatment is ineffective. CONCLUSIONS: It has recently been reported that the prevalence of syphilis is increasing in older individuals, including in patients without HIV infection or prior treatment for early syphilis. Though advanced imaging and molecular biological techniques are often used to help make a diagnosis, they are of limited value. Because the clinical and imaging features are nonspecific, some neurosurgeons do not include cerebral syphilitic gummas in their differential diagnoses. It is vital that this possibility be considered when a patient has a tumour-like cerebral mass and serum positivity for syphilis.

Stroke treatment during the COVID-19 pandemic.

Studies have reported that COVID-19 is associated not only with pneumonia but also with cerebrovascular disease. Consequently, medical personnel involved in treating stroke in the emergency medicine setting have been placed in a situation that requires them to provide treatment while always remaining mindful of the possibility of COVID-19. Here, we describe the current state of stroke treatment during the COVID-19 pandemic. Four patients with stroke and concomitant COVID-19 were treated at our facility. We treated 3 patients with cerebral infarction and 1 patient with cerebral venous sinus thrombosis. All 3 patients with cerebral infarction had a poor outcome. This was attributed in part to the poor general condition of the patients due to concomitant COVID-19, as well as to the severity of the major artery occlusion and cerebral infarction. One patient with cerebral venous sinus thrombosis had a good outcome. Anticoagulant therapy was administered at our hospital and resulted in a stable clinical course. Our hospital has worked to establish an examination and treatment system that enables mechanical thrombectomy to be performed even during the COVID-19 pandemic. We devised a protocol showing the steps to be taken from initial treatment to admission to the cerebral angiography room. Our hospital was able to continue accepting requests for emergency admission thanks to the examination and treatment system we established. Up-to-date information should continue to be collected to create examination and treatment systems.

Detecting task-relevant spatiotemporal modules and their relation to motor adaptation.

How does the central nervous system (CNS) control our bodies, including hundreds of degrees of freedom (DoFs)? A hypothesis to reduce the number of DoFs posits that the CNS controls groups of joints or muscles (i.e., modules) rather than each joint or muscle independently. Another hypothesis posits that the CNS primarily controls motion components relevant to task achievements (i.e., task-relevant components). Although the two hypotheses are examined intensively, the relationship between the two concepts remains unknown, e.g., unimportant modules may possess task-relevant information. Here, we propose a framework of task-relevant modules, i.e., modules relevant to task achievements, while combining the two concepts mentioned above in a data-driven manner. To examine the possible role of the task-relevant modules, we examined the modulation of the task-relevant modules in a motor adaptation paradigm in which trial-to-trial modifications of motor output are observable. The task-relevant modules, rather than conventional modules, showed adaptation-dependent modulations, indicating the relevance of task-relevant modules to trial-to-trial updates of motor output. Our method provides insight into motor control and adaptation via an integrated framework of modules and task-relevant components.

Whole-genome long-read TAPS deciphers DNA methylation patterns at base resolution using PacBio SMRT sequencing technology.

Long-read sequencing provides valuable information on difficult-to-map genomic regions, which can complement short-read sequencing to improve genome assembly, yet limited methods are available to accurately detect DNA methylation over long distances at a whole-genome scale. By combining our recently developed TET-assisted pyridine borane sequencing (TAPS) method, which enables direct detection of 5-methylcytosine and 5-hydroxymethylcytosine, with PacBio single-molecule real-time sequencing, we present here whole-genome long-read TAPS (wglrTAPS). To evaluate the performance of wglrTAPS, we applied it to mouse embryonic stem cells as a proof of concept, and an N50 read length of 3.5 kb is achieved. By sequencing wglrTAPS to 8.2× depth, we discovered a significant proportion of CpG sites that were not covered in previous 27.5× short-read TAPS. Our results demonstrate that wglrTAPS facilitates methylation profiling on problematic genomic regions with repetitive elements or structural variations, and also in an allelic manner, all of which are extremely difficult for short-read sequencing methods to resolve. This method therefore enhances applications of third-generation sequencing technologies for DNA epigenetics.

An Initial High National Institutes of Health Stroke Scale Score and Any Intracranial Hemorrhage Are Independent Factors for a Poor Outcome in Nonagenarians Treated with Thrombectomy for Acute Large Vessel Occlusion: The Tokyo/Tama-REgistry of Acute Endovascular Thrombectomy (TREAT) Study.

BACKGROUND: Mechanical thrombectomy (MT) is effective in acute ischemic stroke patients ≥80 years old with large vessel occlusion (LVO). However, data for patients ≥90 years old remain very limited, and factors influencing functional outcomes are unclear. This study aimed to investigate factors influencing functional outcomes in patients ≥90 years old treated with MT for acute LVO. METHODS: This retrospective observational study used prospectively collected data from the Tokyo/tama-REgistry of Acute endovascular Thrombectomy (TREAT) study. Inclusion criteria were as follows: 1) patients ≥90 years old treated with MT for LVO and 2) prestroke modified Rankin Scale (mRS) score, 0-3. The functional outcome was defined based on the mRS score at 90 days after the procedure: good functional outcome, mRS score 0-3 and poor functional outcome, mRS score 4-6. RESULTS: Data were analyzed for 104 patients ≥90 years old. The good functional outcome was observed in 25 patients (24.0%), and the poor functional outcome was observed in the remaining 79 patients. Significant differences were identified in initial National Institutes of Health Stroke Scale (NIHSS) score, modified Thrombolysis in Cerebral Infarction grade 2b-3, modified Thrombolysis in Cerebral Infarction grade 3, and any intracranial hemorrhage and hemorrhagic infarction in univariate analyses. Multivariable analysis confirmed the initial NIHSS score (odds ratio, 1.08; 95% confidence interval, 1.01-1.17; P = 0.045) and any intracranial hemorrhage (odds ratio, 11.6; 95% confidence interval, 1.43-95.0; P = 0.022) as independent factors for the functional outcome. CONCLUSIONS: An initial high NIHSS score and any intracranial hemorrhage are independent factors for the poor functional outcome in acute ischemic stroke patients ≥90 years old treated with MT.

Creation, effects on embryo quality, and clinical outcomes of a new embryo culture medium with 31 optimized components derived from human oviduct fluid: A prospective multicenter randomized trial.

Purpose: Our aim is to make an ideal embryo culture medium close to human oviduct fluid (HOF) components, and to evaluate the quality of this medium with embryo quality and clinical outcomes in assisted reproductive technology (ART) by a prospective randomized controlled trial (RCT). Methods: Study I: HOF was collected laparoscopically from patients (n = 28) with normal pelvic findings. According to HOF analysis results, the new medium "HiGROW OVIT®" (OVIT) was designed. Study II: Embryos (2 pronuclei (2PN) = 9633) were assigned from 1435 patients. The blastulation rate (BR), good BR (gBR), utilized (transferred/cryo-preserved) BR (uBR), pregnancy rate (PR), and miscarriage rate (MR) were compared between the OVIT and control groups by RCT. Results: The novel medium 'OVIT' was produced according to 31 HOF components. The concentrations of essential amino acids (e-AAs) were lower in OVIT than in current media, yet the opposite was true for ne-AA concentrations. gBR and uBR were higher in the OVIT group than in the control group. In the older female group, gBT and uBR were significantly higher in the OVIT group. Conclusions: The novel medium 'OVIT' was produced according to HOF data. The OVIT had significantly better embryo quality and clinical outcomes than the current media.

Classification of Voice Disorders Using a One-Dimensional Convolutional Neural Network.

OBJECTIVES: Auditory-perceptual voice analysis is a standard method for quantifying pathological voice quality, but perceptual ratings are based on subjective evaluations and therefore may vary among examiners. Although many acoustic metrics have been studied for potential use in the objective evaluation of pathological voices, the interpretation of acoustic metrics in individual cases is difficult and the technique is not widely used by clinicians. The aim of this study was to establish standardized methods to discriminate grade, roughness, breathiness, asthenia, strain (GRBAS) scale scores of pathological voices directly using one-dimensional convolutional neural network (1D-CNN) models. METHODS: We constructed an original dataset utilizing 1,377 voice samples of sustained phonation of the vowel /a/. Each voice sample was rated by three experts according to the GRBAS scale and the median values were used as the correct answer label. We designed an end-to-end 1D-CNN model with a raw voice waveform input having a frame width of 9,600 samples. The models were trained with our original dataset for each GRBAS category individually and the model performance was tested by the five-fold cross validation method. RESULTS: The accuracy, F1 score, and quadratic weighted Cohen's kappa for the testing dataset were determined. The metrics for the G scale showed the most balanced model performance, with high accuracy (0.771) and substantial agreement (kappa = 0.710). The model for the R scale had relatively high accuracy (0.765) and F1 score (0.743) with moderate agreement (kappa = 0.536). The accuracy (0.883) and the F1 score (0.865) for the S scale were the highest among the five categories, whereas the Cohen's kappa was the lowest (0.190). CONCLUSIONS: The end-to-end 1D-CNN models can evaluate overall pathological voice quality with a reliability comparable to human evaluations. The efficiency with which the machine learning models can be trained and evaluated is closely related to the dataset quality.

Intravenous Alteplase is Associated with First Pass Effect in Stent-retriever but not ADAPT Thrombectomy : Post Hoc Analysis of the SKIP Study.

PURPOSE: To investigate the effect of alteplase, either combined with stent-retriever thrombectomy or a direct aspiration first pass technique (ADAPT), in patients with large-vessel occlusion stroke. METHODS: This was a retrospective post hoc analysis of data from The Direct Mechanical Thrombectomy in Acute LVO Stroke (SKIP) study. Patients were divided into two groups according to the first-line thrombectomy technique: stent-retriever and ADAPT. Each group was further divided into two subgroups, namely MT and MT + alteplase. The procedural outcomes, such as first pass effect (FPE) ratio and number of passes, were evaluated. The clinical outcomes included mRS score at 3 months. RESULTS: A total of 180 patients were included (116 in the stent-retriever group and 64 in the ADAPT group). No interaction was detected between the first-line technique and alteplase administration. In the stent-retriever group, after adjusting for factors associated with FPE, the adjusted odds ratio (95% confidence interval) of FPE of the MT + alteplase subgroup versus the MT subgroup was 3.57 (1.5-8.48) and in the ADAPT group it was 1.35 (0.37-4.91). With alteplase, the number of passes decreased with adjusted odds ratios of 0.59 (0.37-0.93) in the stent-retriever group but not in the ADAPT group. In both first-line technique groups, clinical outcomes did not differ between subgroups. CONCLUSION: In the SKIP study, alteplase administration was associated with increased FPE when combined with stent-retriever thrombectomy, but not with ADAPT. We found no differences in the clinical outcomes.

Prior ensemble learning : Theory and application to MR image priors.

PURPOSE: Compressed sensing (CS) reduces the measurement time of magnetic resonance (MR) imaging, where the use of regularizers or image priors are key techniques to boost reconstruction precision. The optimal prior generally depends on the subject and the hand-building of priors is hard. A methodology of combining priors to create a better one would be useful for various forms of image processing that use image priors. METHODS: We propose a theory, called prior ensemble learning (PEL), which combines many weak priors (not limited to images) efficiently and approximates the posterior mean (PM) estimate, which is Bayes optimal for minimizing the mean squared error (MSE). The way of combining priors is changed from that of an exponential family to a mixture family. We applied PEL to an undersampled (10%) multicoil MR image reconstruction task. RESULTS: We demonstrated that PEL could combine 136 image priors (norm-based priors such as total variation (TV) and wavelets with various regularization coefficient (RC) values) from only two training samples and that it was superior to the CS-SENSE-based method in terms of the MSE of the reconstructed image. The resulting combining weights were sparse (18% of the weak priors remained), as expected. CONCLUSION: By the theory, the PM estimator was decomposed into the sparse weighted sum of each weak prior's PM estimator, and the exponential computational complexity for RCs was reduced to polynomial order w.r.t. the number of weak priors. PEL is feasible and effective for a practical MR image reconstruction task.

Impact of Coronavirus Disease 2019 on Time Delay and Functional Outcome of Mechanical Thrombectomy in Tokyo, Japan.

OBJECTIVES: An association has been reported between delays in the onset-to-door (O2D) time for mechanical thrombectomy (MT) and outbreaks of coronavirus disease 2019 (COVID-19). However, the association between other MT time courses or functional outcomes and COVID-19 outbreaks remains unclear. We compared the time courses of stroke pathways or functional outcomes in 2020 (the COVID-19 era) with those in 2019 (the pre-COVID-19 era) in Tokyo, Japan. MATERIALS AND METHODS: This retrospective observational study used data from the Tokyo-tama-REgistry of Acute endovascular Thrombectomy (TREAT), a multicenter registry of MT for acute large vessel occlusion in the Tokyo Metropolitan Area. Patients who had undergone acute MT from January 2019 to December 2020 were included. Patients were classified by the year they had undergone MT (2019 or 2020). RESULTS: In total, 477 patients were analyzed. O2D time was significantly longer in 2020 (146.0 min) than in 2019 (105.0 min; p = 0.034). No significant difference in door-to-puncture time (D2P) time or modified Rankin Scale (mRS) score 0-2 at 90 days was seen between 2019 and 2020. In the subgroup analysis, O2D time was significantly longer in the first half of 2020 compared with 2019. Multivariable logistic regression analysis revealed that the year 2020 was a independent predictor of longer O2D time, but not for mRS score 0-2 at 90 days. CONCLUSIONS: Although O2D time was significantly longer in the COVID-19 compared with the pre-COVID-19 era, D2P may not be significantly delayed and functional outcomes may not be different, despite the COVID-19 pandemic.

Endovascular treatment of acute basilar artery occlusion: Outcomes, influencing factors and imaging characteristics from the Tama-REgistry of acute thrombectomy (TREAT) study.

OBJECTIVE: The effectiveness of mechanical thrombectomy (MT) for acute basilar artery occlusion (ABAO) remains unknown. We evaluated the feasibility, safety, and efficacy of endovascular treatment for ABAO. METHODS: We retrospectively investigated patients with ABAO who underwent MT using modern stent retrievers and an aspiration device between January 2015 and March 2019 at 12 comprehensive stroke centers. Functional outcomes and 90-day mortality rates were analyzed as primary outcomes. Factors influencing outcomes were analyzed as secondary outcomes. Relationships between outcome and affected area of infarction on arrival were also analyzed. RESULTS: Seventy-three patients were included. Good outcome (modified Rankin Scale (mRS) score 0-2) was achieved in 25/73 patients (34.2%) and the all-cause 90-day mortality rate was 23.3% (17/73). Successful recanalization (modified Thrombolysis In Cerebral Infarction grade 2b and 3) was achieved in 70/73 patients (95.9%). In univariate analyses, age, National Institutes of Health Stroke Scale score, and posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) differed significantly between good and poor functional outcome groups. Age and pc-ASPECTS were significantly associated with functional outcomes in the logistic regression model. Positive findings for the midbrain on diffusion-weighted imaging on pc-ASPECTS and brainstem score were significantly associated with poor outcomes. CONCLUSION: MT with modern devices for ABAO resulted in highly successful recanalization and good outcomes. A positive finding for the midbrain on initial imaging might predict poor outcomes. Further studies are required to confirm our results.

High-density mapping of primate digit representations with a 1152-channelµECoG array.

Objective.Advances in brain-machine interfaces (BMIs) are expected to support patients with movement disorders. Electrocorticogram (ECoG) measures electrophysiological activities over a large area using a low-invasive flexible sheet placed on the cortex. ECoG has been considered as a feasible signal source of the clinical BMI device. To capture neural activities more precisely, the feasibility of higher-density arrays has been investigated. However, currently, the number of electrodes is limited to approximately 300 due to wiring difficulties, device size, and system costs.Approach.We developed a high-density recording system with a large coverage (14 × 7 mm2) and using 1152 electrodes by directly integrating dedicated flexible arrays with the neural-recording application-specific integrated circuits and their interposers.Main results.Comparative experiments with a 128-channel array demonstrated that the proposed device could delineate the entire digit representation of a nonhuman primate. Subsampling analysis revealed that higher-amplitude signals can be measured using higher-density arrays.Significance.We expect that the proposed system that simultaneously establishes large-scale sampling, high temporal-precision of electrophysiology, and high spatial resolution comparable to optical imaging will be suitable for next-generation brain-sensing technology.

Subtraction-free and bisulfite-free specific sequencing of 5-methylcytosine and its oxidized derivatives at base resolution.

Although various methods have been developed for sequencing cytosine modifications, it is still challenging for specific and quantitative sequencing of individual modification at base-resolution. For example, to obtain both true 5-methylcytosine (5mC) and true 5-hydroxymethylcytosine (5hmC) information, the two major epigenetic modifications, it usually requires subtraction of two methods, which increases noise and requires high sequencing depth. Recently, we developed TET-assisted pyridine borane sequencing (TAPS) for bisulfite-free direct sequencing of 5mC and 5hmC. Here we demonstrate that two sister methods, TAPSß and chemical-assisted pyridine borane sequencing (CAPS), can be effectively used for subtraction-free and specific whole-genome sequencing of 5mC and 5hmC, respectively. We also demonstrate pyridine borane sequencing (PS) for whole-genome profiling of 5-formylcytosine and 5-carboxylcytosine, the further oxidized derivatives of 5mC and 5hmC. This work completes the set of versatile borane reduction chemistry-based methods as a comprehensive toolkit for direct and quantitative sequencing of all four cytosine epigenetic modifications.