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Karnofsky Performance Status (KPS) is a widely used scale to assess performance status. KPS ≥ 50% implies that patients can live at home. Therefore, maintaining KPS ≥ 50% is important to improve the quality of life of patients with glioblastoma, whose median survival is less than 2 years. This study aimed to identify the factors associated with survival time with maintenance of KPS ≥ 50% (survival with KPS ≥ 50%) in patients with glioblastoma, IDH-wildtype. Ninety-eight patients with glioblastomas, IDH-wildtype, who were treated with concomitant radiotherapy (RT) and temozolomide (TMZ) followed by maintenance TMZ therapy, and whose KPS at the start of RT was ≥ 50%, were included. The median survival with KPS ≥ 50% was 13.3 months. In univariate analysis, preoperative KPS (≥ 80%), KPS at the start of RT (≥ 80%), residual tumor size (< 2 cm 3 ), methylated MGMT promotor, and implantation of BCNU wafer were associated with survival with KPS ≥ 50%. In multivariate analysis, KPS at the start of RT (≥ 80%), methylated MGMT promotor, and residual tumor size (< 2 cm 3 ) were significantly associated with increased survival with KPS ≥ 50%. A strategy of maximum possible tumor resection without compromising KPS is desirable to prolong the survival time with KPS ≥ 50%., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Fujita Health University (Approval No. HM22-434)., (© 2025. The Author(s).)

Facultative heterochromatin is formed by Polycomb repressive complex 2 (PRC2)-deposited H3K27 trimethylation (H3K27me3) and PRC1-deposited H2AK119 mono-ubiquitylation (H2AK119ub1). How it is newly established after fertilization remains unclear. To delineate the establishment kinetics, here we profiled the temporal dynamics of H3K27 dimethylation (H3K27me2), which represents the de novo PRC2 catalysis, in mouse preimplantation embryos. H3K27me2 is newly deposited at CpG islands (CGIs), the paternal X chromosome (Xp) and putative enhancers during the eight-cell-to-morula transition, all of which follow H2AK119ub1 deposition. We found that JARID2, a PRC2.2-specific accessory protein possessing an H2AK119ub1-binding ability, colocalizes with SUZ12 at CGIs and Xp in morula embryos. Upon JARID2 depletion, SUZ12 chromatin binding and H3K27me2 deposition were attenuated and H3K27 acetylation at putative enhancers was increased in morulae and subsequently H3K27me3 failed to be deposited in blastocysts. These data reveal that facultative heterochromatin is established by PRC2.2-driven stepwise H3K27 methylation along pre-deposited H2AK119ub1 during early embryogenesis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

According to Couinaud's definition, the cranial boundary of the caudate lobe is delineated by the three major hepatic veins. However, many branches of the caudate lobe go through the ceiling that is composed of these hepatic veins. The cranial boundary of the caudate lobe should be determined by employing the portal segmentation. We conducted a study based on the dissection of 37 colored resin liver casts to reveal the caudate branches of the liver. The paracaval portal vein branches (PCPvs) were defined as cranial portal branches from the main trunk or first-order branch of the portal vein distributed in front of the inferior vena cava, according to Kumon's classification. The PCVs were traced to reveal the cranial boundary of the caudate lobe. Results showed that in 18 cases (49%), the PCPvs reached the liver surface through the gap between the right and middle hepatic veins (type RM, n = 11), between the tiny branches of the middle hepatic vein (type M, n = 4), and between the middle and left hepatic veins (type ML, n = 3). The PCPvs did not reach the liver surface in 19 cases (type 0). No PCPvs reached the hepatic surface behind the right hepatic vein. Half of the PCPvs in the liver reached the hepatic surface beyond the boundary composed of the three major hepatic veins. Recognition of the PCPvs in the liver is indispensable to perform anatomically precise liver resections involving the major hepatic veins., Competing Interests: The authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)

Very long-chain fatty acids (VLCFAs) are degraded exclusively in peroxisomes, as evidenced by the accumulation of VLCFAs in patients with certain peroxisomal disorders. Although accumulation of VLCFAs is considered to be associated with health issues, including neuronal degeneration, the mechanisms underlying VLCFAs-induced tissue degeneration remain unclear. Here, we report the toxic effect of VLCFA and protective effect of C18: 1 FA in peroxisome-deficient CHO cells. We examined the cytotoxicity of saturated and monounsaturated VLCFAs with chain-length at C20-C26, and found that longer and saturated VLCFA showed potent cytotoxicity at lower accumulation levels. Furthermore, the extent of VLCFA-induced toxicity was found to be associated with a decrease in cellular C18:1 FA levels. Notably, supplementation with C18:1 FA effectively rescued the cells from VLCFA-induced apoptosis without reducing the cellular VLCFAs levels, implying that peroxisome-deficient cells can survive in the presence of accumulated VLCFA, as long as the cells keep sufficient levels of cellular C18:1 FA. These results suggest a therapeutic potential of C18:1 FA in peroxisome disease and may provide new insights into the pharmacological effect of Lorenzo's oil, a 4:1 mixture of C18:1 and C22:1 FA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Foraminal stenosis is one of the types of lumbar spinal stenosis. The pathology can be treated minimally invasively by full-endoscopic spine surgery (FESS). The final challenge in transforaminal FESS is foraminal stenosis in patients with stable isthmic spondylolisthesis at L5. This article provides a step-by-step explanation of how to achieve complete decompression. A cannula of 8 mm in diameter is docked at the base of the superior articular process of the sacrum. The pars crisscross that consists of the superior articular process at S1, the floating lamina, the inferior articular process at L4, and the pars ragged edge is then clearly seen endoscopically. Visualization of the pars crisscross is key to successful decompression. Starting with the superior articular process at S1, followed by partial removal of the floating lamina. Next, the tip of the inferior articular process at L4 is removed. The pars ragged edge is then carefully shaved. Finally, decompression of the exiting nerve root at L5 is confirmed. This report provides the first step-by step description of full-endoscopic decompression of foraminal stenosis under local anesthesia in patients with stable L5 isthmic spondylolisthesis, which we have named "full-endoscopic pars crisscross decompression". J. Med. Invest. 71 : 191-196, August, 2024.

The paracaval portion (PC) of the caudate lobe is a small area of the liver located in front of the inferior vena cava. Conventional right hemihepatectomy (RH) along the Rex-Cantlie line involves resection of not only the anterior and posterior sections but also the PC behind the middle hepatic vein (MHV). However, to preserve the future liver remnant volume as much as possible, PC-preserving RH may be beneficial in selected patients. We injected an indocyanine green (ICG) solution in the PC portal branch under intraoperative ultrasonography (IOUS) guidance and performed an RH preserving the fluorescently visible PC in a patient with liver metastasis. The patient was a 47-year-old male with a 24 ×10 cm metastatic hepatic tumor from sigmoid colon cancer. CT volumetry revealed that the left hemiliver excluding the caudate lobe was 55%, and the caudate lobe was 5.3%. Before hepatic transection, the ICG solution was injected into the PC portal branch under IOUS guidance. During hepatic transection, the PC was identified as a fluorescent area behind the MHV using a near-infrared imaging system. Thus, the anatomical right-side boundary of the caudate lobe was clearly found. Following RH, the PC was preserved as a fluorescently visible area. The patient had an uneventful recovery. RH preserving the fluorescently visible PC of the liver is a feasible procedure., Competing Interests: The authors have no conflicts of interest to disclose., (2023, National Center for Global Health and Medicine.)

Fence-post catheter techniques are used to use tumor margins when resecting gliomas. In the present study, deep electrodes instead of catheters were used as fence-posts. The case of a 25-year-old female patient whose magnetic resonance images (MRI) revealed a tumor in the left cingulate gyrus is presented in this study. She underwent daily seizures without loss of consciousness under the administration of anti-seizure medications. Despite video electroencephalography (EEG) monitoring, the scalp inter-ictal EEG did not show obvious epileptiform discharges. We were consequently uncertain whether such frequent seizures were epileptic seizures or not. As a result, deep electrodes were used as fence-posts: three deep electrodes were inserted into the tumor's anterior, lateral, and posterior margins using a navigation-guided method. The highest epileptic discharge was detected from the anterior deep electrode. As a result, ahead of the tumor was extendedly resected, and epileptic discharges were eliminated using EEG. The postoperative MRI revealed that the tumor was resected. The patient has never experienced seizures after the surgery. In conclusion, when supratentorial gliomas complicated by frequent seizures are resected, intraoperative EEG monitoring using deep electrodes as fence-posts is useful for estimating epileptogenic areas.

Vagus nerve stimulation (VNS) is an effective surgical option for intractable epilepsy. Although the surgical procedure is not so complicated, vagus nerve detection is sometimes difficult due to its anatomical variations, which may lead to surgical manipulation-associated complications. Thus, this study aimed to visualize the vagus nerve location preoperatively by fused images of three-dimensional computed tomography angiography (3D-CTA) and magnetic resonance imaging (MRI). This technique was applied to two cases. The neck 3D-CTA and MRI were performed, and the fused images were generated using the software. The vagus nerve and its anatomical relationship with the internal jugular vein (IJV) and common carotid artery were clearly visualized. The authors predicted that the vagus nerve was detected by laterally pulling the IJV according to the images. Intraoperatively, the vagus nerve was located as the authors predicted. The time of the surgery until the vagus nerve detection was <60 min in both cases. This novel radiological technique for visualizing the vagus nerve is effective to quickly detect the vagus nerve, which has anatomical variations, during the VNS.

Distinguishing primary central nervous system lymphoma (PCNSL) from glioblastoma, isocitrate dehydrogenase (IDH)-wildtype is sometimes hard. Because the role of operation on them varies, accurate preoperative diagnosis is crucial. In this study, we evaluated whether a specific kind of chemical exchange saturation transfer imaging, i.e., amide proton transfer-weighted (APTw) imaging, was useful to distinguish PCNSL from glioblastoma, IDH-wildtype. A total of 14 PCNSL and 27 glioblastoma, IDH-wildtype cases were evaluated. There was no significant difference in the mean APTw signal values between the two groups. However, the percentile values from the 1st percentile to the 20th percentile APTw signals and the width 1-100 APTw signals significantly differed. The highest area under the curve was 0.796, which was obtained from the width 1-100 APTw signal values. The sensitivity and specificity values were 64.3% and 88.9%, respectively. APTw imaging was useful to distinguish PCNSL from glioblastoma, IDH-wildtype. To avoid unnecessary aggressive surgical resection, APTw imaging is recommended for cases in which PCNSL is one of the differential diagnoses.

Omidenepag isopropyl (OMDI) is an intraocular pressure (IOP)-lowering drug used to treat glaucoma. The active form of OMDI, omidenepag (OMD), lowers elevated IOP, the main risk factor for glaucoma, by increasing the aqueous humor outflow; however, a detailed understanding of this mechanism is lacking. To clarify the IOP-lowering mechanism of OMDI, the effects of OMD on the mRNA expression of the extracellular matrix, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were evaluated in human trabecular meshwork cells. Under 2D culture conditions, the mRNA expression of FN1, COL1A1, COL1A2, COL12A1, and COL13A1 decreased in a concentration-dependent manner after 6 or 24 h treatment with 10 nM, 100 nM, and 1 μM OMD, while that of COL18A1 decreased after 6 h treatment with 1 μM OMD. Significant changes in expression were observed for many MMP and TIMP genes. Under 3D culture conditions, the extracellular matrix-related genes COL12A1 and COL13A1 were downregulated by OMD treatment at all three concentrations. Under both 2D and 3D culture conditions, COL12A1 and COL13A1 were downregulated following OMD treatment. Reduction in the extracellular matrix contributes to the decrease in outflow resistance, suggesting that the downregulation of the two related genes may be one of the factors influencing the IOP-lowering effect of OMDI. Our findings provide insights for the use of OMDI in clinical practice., Competing Interests: Competing Interests Statement: All authors declare no non-financial competing interests. Their commercial affiliation to Santen Pharmaceutical Co., Ltd. and UBE Corporation does not alter their adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Kumon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In female mammals, one of the two X chromosomes becomes inactivated during development by X-chromosome inactivation (XCI). Although Polycomb repressive complex (PRC) 1 and PRC2 have both been implicated in gene silencing, their exact roles in XCI during in vivo development have remained elusive. To this end, we have studied mouse embryos lacking either PRC1 or PRC2. Here we demonstrate that the loss of either PRC has a substantial impact on maintenance of gene silencing on the inactive X chromosome (Xi) in extra-embryonic tissues, with overlapping yet different genes affected, indicating potentially independent roles of the two complexes. Importantly, a lack of PRC1 does not affect PRC2/H3K27me3 accumulation and a lack of PRC2 does not impact PRC1/H2AK119ub1 accumulation on the Xi. Thus PRC1 and PRC2 contribute independently to the maintenance of XCI in early post-implantation extra-embryonic lineages, revealing that both Polycomb complexes can be directly involved and differently deployed in XCI., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Selection of high-quality embryos is important to achieve successful pregnancy in assisted reproductive technology (ART). Recently, it has been debated whether RNA-sequencing (RNA-Seq) should be applied to ART to predict embryo quality. However, information on genes that can serve as markers for pregnant expectancy is limited. Furthermore, there is no information on which transcriptome of trophectoderm (TE) or inner cell mass (ICM) is more highly correlated with pregnant expectancy. Here, we performed RNA-Seq analysis of TE and ICM of human blastocysts, the pregnancy expectation of which was retrospectively determined using the clinical outcomes of 1,890 cases of frozen-thawed blastocyst transfer. We identified genes that were correlated with the expected pregnancy rate in ICM and TE, respectively, with a larger number of genes identified in TE than in ICM. Downregulated genes in the TE of blastocysts that were estimated to have lower expectation of pregnancy included tight junction-related genes such as CXADR and ATP1B1, which have been implicated in peri-implantation development. Moreover, we identified dozens of differentially expressed genes by regrouping the blastocysts based on the maternal age and the Gardner score. Additionally, we showed that aneuploidy estimation using RNA-Seq datasets does not correlate with pregnancy expectation. Thus, our study provides an expanded list of candidate genes for the prediction of pregnancy in human blastocyst embryos., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Kai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This paper proposes the use of the standing waves created by the interference between transmitted and reflected acoustic signals to recognize the size and the shape of a target object. This study shows that the profile of the distance spectrum generated by the interference encodes not only the distance to the target, but also the distance to the edges of the target surface. To recognize the extent of the surface, a high-resolution distance spectrum is proposed, and a method to estimate the points on the edges by incorporating observations from multiple measurement is introduced. Numerical simulations validated the approach and showed that the method worked even in the presence of noise. Experimental results are also shown to verify that the method works in a real environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kumon, Fukunaga, Manabe and Nakatsuma.)

Genomic imprinting regulates parental origin-dependent monoallelic gene expression. It is mediated by either germline differential methylation of DNA (canonical imprinting) or oocyte-derived H3K27me3 (noncanonical imprinting) in mice. Depletion of Eed, an essential component of Polycomb repressive complex 2, results in genome-wide loss of H3K27me3 in oocytes, which causes loss of noncanonical imprinting (LOI) in embryos. Although Eed maternal KO (matKO) embryos show partial lethality after implantation, it is unknown whether LOI itself contributes to the developmental phenotypes of these embryos, which makes it unclear whether noncanonical imprinting is developmentally relevant. Here, by combinatorial matKO of Xist , a noncanonical imprinted gene whose LOI causes aberrant transient maternal X-chromosome inactivation (XCI) at preimplantation, we show that prevention of the transient maternal XCI greatly restores the development of Eed matKO embryos. Moreover, we found that the placentae of Eed matKO embryos are remarkably enlarged in a manner independent of Xist LOI. Heterozygous deletion screening of individual autosomal noncanonical imprinted genes suggests that LOI of the Sfmbt2 miRNA cluster chromosome 2 miRNA cluster (C2MC), solute carrier family 38 member 4 ( Slc38a4 ), and Gm32885 contributes to the placental enlargement. Taken together, our study provides evidence that Xist imprinting sustains embryonic development and that autosomal noncanonical imprinting restrains placental overgrowth., (© 2022 Matoba et al.; Published by Cold Spring Harbor Laboratory Press.)

There have been historical arguments about the boundary of the caudate lobe of the liver. Kumon M first advocated the definition of the caudate lobe based on the portal segmentation of the liver in 1985, and classified it into three parts, Spiegel lobe, paracaval portion and caudate process. Prof. Couinaud defined the dorsal liver as a union of segments I and IX in 1994, based on the spatial position to the major hepatic veins, hilar plate and inferior vena cava. In Couinaud's classification, right-side of the dorsal liver is supplied by the branches from the posterior and anterior sections. In the present study using a liver cast, we found a paracaval branch of the portal vein branching from the right portal vein on the dissecting plain along the Rex-Cantlie's line. We also found several branches from the posterior portal vein to the right-side of the paracaval portion, but they should be defined to belong to the posterior sections., Competing Interests: The authors have no conflicts of interest to disclose., (2022, National Center for Global Health and Medicine.)

Enteral nutrition (EN) is a rational approach to providing nutritional intake via the intestines in patients who are unable to tolerate parenteral nutrition. We conducted a preliminary study to investigate the effects of EN on the intestinal environment in 10 patients in a persistent vegetative state (PVS) ( n = 5 each in the EN and EN with probiotics; Clostridium butyricum MIYAIRI 588 ) groups compared with 10 healthy controls. The results of 16S amplicon sequencing of the intestinal microbiota showed that EN led to dysbiosis with a decrease in α-diversity and an obvious change in β-diversity. A particularly significant decrease was seen in useful intestinal bacteria such as Bifidobacterium and butyrate-producing bacteria. Analysis of intestinal metabolites also supported these results, showing significant decreases in butyric and pyruvic acid after EN. Although C. butyricum MIYAIRI 588 improved some intestinal metabolites that were decreased after EN, it did not improve the dysbiosis of the intestinal microbiota. These findings indicate that EN causes dysbiosis of the intestinal microbiota and an imbalance in some intestinal metabolites in patients in a PVS. Moreover, although C. butyricum MIYAIRI 588 improved the imbalance of some intestinal metabolites after EN, it did not prevent dysbiosis of the intestinal microbiota.

The mammalian blastocyst consists of three distinct cell types: epiblast, trophoblast (TB), and primitive endoderm (PrE). Although embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) retain the functional properties of epiblast and TB, respectively, stem cells that fully recapitulate the developmental potential of PrE have not been established. Here, we report derivation of primitive endoderm stem cells (PrESCs) in mice. PrESCs recapitulate properties of embryonic day 4.5 founder PrE, are efficiently incorporated into PrE upon blastocyst injection, generate functionally competent PrE-derived tissues, and support fetal development of PrE-depleted blastocysts in chimeras. Furthermore, PrESCs can establish interactions with ESCs and TSCs and generate descendants with yolk sac-like structures in utero. Establishment of PrESCs will enable the elucidation of the mechanisms for PrE specification and subsequent pre- and postimplantation development.

Background: A common surgical approach for dominant insular lesions is to make a surgical corridor in asymptomatic cortices based on functional mapping. However, the surgical approach is difficult for posterior insular lesions in a dominant hemisphere because the posterior parts of the perisylvian cortices usually have verbal functions., Observations: We present the case of a 40-year-old male whose magnetic resonance images revealed the presence of contrast-enhancing lesions in the left posterior insula. Our surgical approach was to split the sylvian fissure as widely as possible, and partially resect Heschl's gyrus if the cortical mapping was negative for language tests. Because Heschl's gyrus did not have verbal functions, the gyrus was used as a surgical corridor. It was wide enough for the removal of the lesion; however, because intraoperative pathological diagnosis eliminated the possibility of brain tumors, further resection was discontinued. The tissues were histologically diagnosed as tuberculomas. Antituberculosis drugs were administered, and the residual lesions finally disappeared. According to the neurophysiological tests, the patient showed temporary impairment of auditory detection, but the low scores of these tests improved., Lessons: The transsylvian and trans-Heschl's gyrus approach can be a novel surgical option for excising dominant posterior insular lesions.