Impaired humoral immunity following COVID-19 vaccination in HTLV-1 carriers.

BACKGROUND: Whether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown. METHODS: To investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors. RESULTS: We analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers. CONCLUSIONS: The humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them.

Hydroxy-directed peptide bond formation from α-amino acid-derived inert esters enabled by boronic acid catalysis.

A boronic acid-catalyzed peptide bond formation from α-amino acid methyl esters is described. The catalysis showed high chemoselectivity for ß-hydroxy-α-amino esters, affording the peptides in high to excellent yields with high functional group tolerance. This hydroxy-directed peptide bond formation could be applicable to oligopeptide syntheses. This is the first successful example of organoboron-catalyzed peptide bond formation from α-amino acid-derived inert esters.

Challenges in the diagnosis of the enigmatic primary adrenal leiomyosarcoma: two case reports and review of the literature.

BACKGROUND: Primary adrenal leiomyosarcoma is a rare and aggressive mesenchymal tumor derived from the smooth muscle wall of a central adrenal vein or its tributaries; therefore, tumors tend to invade the inferior vena cava and cause thrombosis. The great majority of tumors grow rapidly, which makes the disease difficult to diagnose in its early clinical stages and needs differentiation from adrenocortical carcinomas for the selection of chemotherapy including mitotane which causes adrenal insufficiency. CASE PRESENTATION: We presented two patients with adrenal leiomyosarcoma who were referred to our hospital with abdominal pain and harboring large adrenal tumors and inferior vena cava thrombosis. The endocrine findings, including serum catecholamine levels, were unremarkable. These two patients were considered clinically inoperable, and CT-guided core needle biopsy was performed to obtain the definitive histopathological diagnosis and determine the modes of therapy. The masses were subsequently diagnosed as primary adrenal leiomyosarcoma based on the histological features and positive immunoreactivity for SMA (smooth muscle actin), desmin, and vimentin. CONCLUSIONS: Adrenal leiomyosarcoma derived from the smooth muscle wall of a central adrenal vein or its tributaries is rare but should be considered a differential diagnosis in the case of nonfunctioning adrenal tumors extending directly to the inferior vena cava. CT-guided biopsy is considered useful for histopathological diagnosis and clinical management of patients with inoperable advanced adrenal tumors without any hormone excess.

Synaptic crossroads: navigating the circuits of movement.

The anterior lateral motor area (ALM) is crucial in preparing and executing voluntary movements through its diverse neuronal subpopulations that target different subcortical areas. A recent study by Xu et al. utilized an elaborate viral tracing strategy in mice to provide comprehensive whole-brain maps of monosynaptic inputs to the major descending pathways of ALM.

Bleeding-Source Exploration in Subdural Hematoma: Observational Study on the Usefulness of Postmortem Computed Tomography Angiography.

In a few cases, postmortem computed tomography angiography (PMCTA) is effective in postmortem detection of cortical artery rupture causing subdural hematoma (SDH), which is difficult to detect at autopsy. Here, we explore the usefulness and limitations of PMCTA in detecting the sites of cortical arterial rupture for SDH. In 6 of 10 cases, extravascular leakage of contrast material at nine different places enabled PMCTA to identify cortical arterial rupture. PMCTA did not induce destructive arterial artifacts, which often occur during autopsy. We found that, although not in all cases, PMCTA could show the site of cortical arterial rupture causing subdural hematoma in some cases. This technique is beneficial for cases of SDH autopsy, as it can be performed nondestructively and before destructive artifacts from the autopsy occur.

Catalytic dehydrative amide bond formation using aqueous ammonia: synthesis of primary amides utilizing diboronic acid anhydride catalysis.

Although aqueous ammonia is an inexpensive and readily available safe source of ammonia, there have been no successful studies on direct catalytic dehydrative amidations of carboxylic acids with aqueous ammonia. In this study, we report a catalytic methodology for the synthesis of primary amides through diboronic acid anhydride (DBAA)-catalyzed dehydrative condensation of carboxylic acids with aqueous ammonia as the amine substrate.

Predictive discriminative accuracy of walking abilities at discharge for community ambulation levels at 6 months post-discharge among inpatients with subacute stroke.

[Purpose] This study aimed to compare the predictive accuracy of walking ability at discharge among subacute stroke inpatients at 6 months post-discharge in terms of community ambulation level and establish optimal cut-off values. [Participants and Methods] This prospective observational study included 78 patients who completed follow-up assessments. Patients were classified into three groups based on the Modified Functional Walking Category (household/most limited community walkers, least limited community walkers, and unlimited community walkers) obtained by telephone survey at 6 months post-discharge. Predictive accuracy and cut-off values for discriminating among groups were calculated from 6-minute walking distance and comfortable walking speed measured at the time of discharge using receiver operating characteristic curves. [Results] Between household/most limited and least limited community walkers, 6-minute walking distance and comfortable walking speed offered similar predictive accuracy (area under the curve, 0.6-0.7), with cut-off values of 195 m and 0.56 m/s, respectively. Between least limited and unlimited community walkers, the areas under the curve were 0.896 for 6-minute walking distance and 0.844 for comfortable walking speed, with cut-off values of 299 m and 0.94 m/s, respectively. [Conclusion] Walking endurance and walking speed among inpatients with subacute stroke provided superior predictive accuracy for unlimited community walkers at 6 months post-discharge.

Relationship between absorbed dose and changes in liver volume after chemoradiotherapy for esophageal cancer.

PURPOSE: The liver is the largest organ in the abdomen and is often irradiated in radiotherapy for non-hepatic malignancies. As most of the studies on changes in liver volume are on hepatocellular carcinoma based on liver dysfunction, there are few studies on healthy liver. In this study, we investigated the relationship between absorbed dose and changes in liver volume after chemoradiotherapy for esophageal cancer in patients without apparent pre-treatment liver dysfunction. MATERIALS AND METHODS: Liver volume was compared between pre-treatment, acute (< 4 months) and late post-treatment (≥ 4 and < 13 months) phases in 12 patients using abdominal plain CT images. Volume changes were evaluated separately for the right and left lobes. We investigated the relationship between the volume change and VxGy (percentage of volume received x Gy or more dose). In addition, volume change for each absorbed dose was investigated using deformable image registration. RESULTS: The volume of the left lobe showed a significant decrease between pre-treatment and acute post-treatment phases (p < 0.001), while the volume of right lobe and between acute and late post-treatment phase of left lobe did not. The mean value of the volume reduction rate of the left lobe was 51.1% and equivalent to the mean value of V30Gy. As a result of the volume change for each absorbed dose, the volume reduction rate increased as the absorbed dose increased, and a significant volume loss was observed at doses above 11 Gy. CONCLUSION: Volume of the liver significantly decreased only in the acute phase after chemoradiotherapy for esophageal cancer. The tolerable dose for a healthy liver is generally considered to be 30 Gy, but attention should be paid to lower doses to avoid radiation-induced liver injury.

Detection and Morphological Analysis of Micro-Ruptured Cortical Arteries in Subdural Hematoma: Three-Dimensional Visualization Using the Tissue-Clearing Clear, Unobstructed, Brain/Body Imaging Cocktails and Computational Analysis Method.

One of the causes of bleeding in subdural hematoma is cortical artery rupture, which is difficult to detect at autopsy. Therefore, reports of autopsy cases with this condition are limited and hence, the pathogenesis of subdural hematoma remains unclear. Herein, for the detection and morphological analysis of cortical artery ruptures as the bleeding sources of subdural hematoma, we used the tissue-clearing CUBIC (clear, unobstructed, brain/body imaging cocktails and computational analysis) method with light-sheet fluorescence microscopy and reconstructed the two-dimensional and three-dimensional images. Using the CUBIC method, we could clearly visualize and detect cortical artery ruptures that were missed by conventional methods. Indeed, the CUBIC method enables three-dimensional morphological analysis of cortical arteries including the ruptured area, and the creation of cross-sectional two-dimensional images in any direction, which are similar to histopathological images. This highlights the effectiveness of the CUBIC method for subdural hematoma analysis.

Dendritic Mechanisms for In Vivo Neural Computations and Behavior.

Dendrites receive the vast majority of a single neuron's inputs, and coordinate the transformation of these signals into neuronal output. Ex vivo and theoretical evidence has shown that dendrites possess powerful processing capabilities, yet little is known about how these mechanisms are engaged in the intact brain or how they influence circuit dynamics. New experimental and computational technologies have led to a surge in interest to unravel and harness their computational potential. This review highlights recent and emerging work that combines established and cutting-edge technologies to identify the role of dendrites in brain function. We discuss active dendritic mediation of sensory perception and learning in neocortical and hippocampal pyramidal neurons. Complementing these physiological findings, we present theoretical work that provides new insights into the underlying computations of single neurons and networks by using biologically plausible implementations of dendritic processes. Finally, we present a novel brain-computer interface task, which assays somatodendritic coupling to study the mechanisms of biological credit assignment. Together, these findings present exciting progress in understanding how dendrites are critical for in vivo learning and behavior, and highlight how subcellular processes can contribute to our understanding of both biological and artificial neural computation.

Neocortical layer 5 subclasses: From cellular properties to roles in behavior.

Layer 5 (L5) serves as the main output layer of cortical structures, where long-range projecting pyramidal neurons broadcast the columnar output to other cortical and extracortical regions of the brain. L5 pyramidal neurons are grouped into two subclasses based on their projection targets; while intratelencephalic (IT) neurons project to cortical areas and the striatum, extratelencephalic (ET) neurons project to subcortical areas such as the thalamus, midbrain, and brainstem. Each L5 subclass possesses distinct morphological and electrophysiological properties and is incorporated into a unique synaptic network. Thanks to recent advances in genetic tools and methodologies, it has now become possible to distinguish between the two subclasses in the living brain. There is increasing evidence indicating that each subclass plays a unique role in sensory processing, decision-making, and learning. This review first summarizes the anatomical and physiological properties as well as the neuromodulation of IT and ET neurons in the rodent neocortex, and then reviews recent literature on their roles in sensory processing and rodent behavior. Our ultimate goal is to provide a comprehensive understanding of the role of each subclass in cortical function by examining their operational regimes based on their cellular properties.

Development of individual identification method using thoracic vertebral features as biometric fingerprints.

Identification of individuals is performed when a corpse is found after a natural disaster, incident, or accident. DNA and dental records are frequently used as biometric fingerprints; however, identification may be difficult in some cases due to decomposition or damage to the corpse. The present study aimed to develop an individual identification method using thoracic vertebral features as a biological fingerprint. In this method, the shortest diameter in height, width, and depth of the thoracic vertebrae in the postmortem image and a control antemortem were recorded and a database was compiled using this information. The Euclidean distance or the modified Hausdorff distance was calculated as the distance between two points on the three-dimensional feature space of these measurement data. The thoracic vertebrae T1-12 were measured and the pair with the smallest distance was considered to be from the same person. The accuracy of this method for identifying individuals was evaluated by matching images of 82 cases from a total of 702 antemortem images and showed a hit ratio of 100%. Therefore, this method may be used to identify individuals with high accuracy.

Development of an automatic multiplanar reconstruction processing method for head computed tomography.

BACKGROUND: Head computed tomography (CT) is a commonly used imaging modality in radiology facilities. Since multiplanar reconstruction (MPR) processing can produce different results depending on the medical staff in charge, there is a possibility that the antemortem and postmortem images of the same person could be assessed and identified differently. OBJECTIVE: To propose and test a new automatic MPR method in order to address and overcome this limitation. METHODS: Head CT images of 108 cases are used. We employ the standardized transformation of statistical parametric mapping 8. The affine transformation parameters are obtained by standardizing the captured CT images. Automatic MPR processing is performed by using this parameter. The sphenoidal sinus of the orbitomeatal cross section of the automatic MPR processing of this study and the conventional manual MPR processing are cropped with a matrix size of 128×128, and the value of zero mean normalized correlation coefficient is calculated. RESULTS: The computed zero mean normalized cross-correlation coefficient (Rzncc) of≥0.9, 0.8≤Rzncc < 0.9 and 0.7≤Rzncc < 0.8 are achieved in 105 cases (97.2%), 2 cases (1.9%), and 1 case (0.9%), respectively. The average Rzncc was 0.96±0.03. CONCLUSION: Using the proposed new method in this study, MPR processing with guaranteed accuracy is efficiently achieved.

PROS1 variant in sudden death case of pulmonary embolism caused by calcification in the inferior vena cava: The importance of postmortem genetic analysis.

A Japanese man in his 30s died suddenly. Postmortem computed tomography and autopsy revealed a pulmonary embolism from an organizing thrombus in the inferior vena cava as the cause of death. Genomic analysis of congenital thrombophilia-related genes (i.e., SERPINC1, PROC, PROS1, F2, F5, PLG, and MTHFR) revealed a heterozygous variant of PROS1 (p.A139V), which has been reported in patients with congenital protein S deficiency. After a genetic conference that included forensic pathologists, molecular scientists, genetic researchers, genetic clinicians, and clinical physicians, the results of the genetic analysis were explained to the family. Biochemical analyses of protein S (PS) activity and total PS antigen levels were performed with samples from the deceased's family and genetic analysis was not performed until clinical symptoms appear. Herein we demonstrate the importance of genetic background in cases of a sudden death due to pulmonary embolism.

The usefulness of postmortem computed tomography angiography for subdural hematoma caused by rupture of the cortical artery: A report of two autopsy cases and a literature review.

Acute subdural hematoma (SDH) occurs following severe head trauma with brain contusion or rupture of bridging veins. Conversely, SDH caused by rupture of a cortical artery without trauma or with minor trauma is also possible. Although over 180 cases of the latter SDH have been reported, they were predominantly diagnosed only during surgery, and therefore, no adequate histological evaluation has been performed. Therefore, essential etiology of this SDH type has remained unclear. In addition, the scarcity of autopsy cases may be attributed to arterial rupture being missed if the microscopic findings are too minimal to detect during autopsy. Here, we describe two autopsy cases of SDH of cortical artery origin. Extravasation on postmortem computed tomography angiography and arterial leakage on macroscopic observation during autopsy facilitated detection of the ruptured artery and allowed detailed histological evaluation of the ruptured artery and adjacent dura mater. The etiology of arterial rupture is briefly described on the basis of histopathological findings in this study and the available literature.

Thalamic input to motor cortex facilitates goal-directed action initiation.

Prompt execution of planned motor action is essential for survival. The interactions between frontal cortical circuits and the basal ganglia are central to goal-oriented action selection and initiation.1-4 In rodents, the ventromedial thalamic nucleus (VM) is one of the critical nodes that conveys the output of the basal ganglia to the frontal cortical areas including the anterior lateral motor cortex (ALM).5-9 Recent studies showed the critical role of ALM and its interplay with the motor thalamus in preparing sensory-cued rewarded movements, specifically licking.10-12 Work in primates suggests that the basal ganglia output to the motor thalamus transmits an urgency or vigor signal,13-15 which leads to shortened reaction times and faster movement initiation. As yet, little is known about what signals are transmitted from the motor thalamus to the cortex during cued movements and how these signals contribute to movement initiation. In the present study, we employed a tactile-cued licking task in mice while monitoring reaction times of the initial lick. We found that inactivation of ALM delayed the initiation of cued licking. Two-photon Ca2+ imaging of VM axons revealed that the majority of the axon terminals in ALM were transiently active during licking. Their activity was predictive of the time of the first lick. Chemogenetic and optogenetic manipulation of VM axons in ALM indicated that VM inputs facilitate the initiation of cue-triggered and impulsive licking in trained mice. Our results suggest that VM thalamocortical inputs increase the probability and vigor of initiating planned motor responses.

Boronic Acid-Catalyzed Regioselective Koenigs-Knorr-Type Glycosylation.

Boronic acid-catalyzed regioselective Koenigs-Knorr-type glycosylation is presented. The reaction of an unprotected or partially protected glycosyl acceptor with a glycosyl halide donor in the presence of silver oxide and a low catalytic amount of imidazole-containing boronic acid was found to proceed smoothly, which enables construction of a 1,2-trans glycosidic linkage with high regioselectivities. This is the first example of the use of a boronic acid catalyst to initiate regioselective glycosylation via the activation of cis-vicinal diols in glycosyl acceptors.

Functional Multiple-Spine Calcium Imaging from Brain Slices.

Most excitatory inputs arrive at dendritic spines in a postsynaptic neuron. To understand dendritic information processing, it is critical to scrutinize the spatiotemporal dynamics of synaptic inputs along dendrites. This protocol combines spinning-disk confocal imaging with whole-cell patch-clamp recording to perform wide-field, high-speed optical recording of synaptic inputs in a neuron loaded with a calcium indicator in ex vivo cultured networks. Our protocol enables simultaneous detection of synaptic inputs as calcium signals from hundreds of spines in multiple dendritic branches. For complete details on the use and execution of this protocol, please refer to Takahashi et al. (2012, 2016), Kobayashi et al. (2019), and Ishikawa and Ikegaya (2020).

Perirhinal input to neocortical layer 1 controls learning.

Hippocampal output influences memory formation in the neocortex, but this process is poorly understood because the precise anatomical location and the underlying cellular mechanisms remain elusive. Here, we show that perirhinal input, predominantly to sensory cortical layer 1 (L1), controls hippocampal-dependent associative learning in rodents. This process was marked by the emergence of distinct firing responses in defined subpopulations of layer 5 (L5) pyramidal neurons whose tuft dendrites receive perirhinal inputs in L1. Learning correlated with burst firing and the enhancement of dendritic excitability, and it was suppressed by disruption of dendritic activity. Furthermore, bursts, but not regular spike trains, were sufficient to retrieve learned behavior. We conclude that hippocampal information arriving at L5 tuft dendrites in neocortical L1 mediates memory formation in the neocortex.

Synthesis of Weinreb amides using diboronic acid anhydride-catalyzed dehydrative amidation of carboxylic acids.

The first successful example of the direct synthesis of Weinreb amides using catalytic hydroxy-directed dehydrative amidation of carboxylic acids using the diboronic acid anhydride catalyst is described. The methodology is applicable to the concise syntheses of eight α-hydroxyketone natural products, namely, sattabacin, 4-hydroxy sattabacin, kurasoins A and B, soraphinols A and B, and circumcins B and C.