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JLab E12-19-002 Experiment is planned to measure the Λ-binding energies of 3ΛH [Jπ = 1/2+ or 3/2+(T = 0)] and 4ΛH (1+) at JLab Hall C. The expected accuracy for the binding-energy measurement is |ΔBtotal Λ | ≃ 70 keV. The accurate spectroscopy for these light hypernuclei would shed light on the puzzle of the small binding energy and short lifetime of 3ΛH, and the chargesymmetry breaking in the ΛN interaction. We aim to perform the experiment in 2025.

An n n Λ , which consists of two neutrons and a Lambda hyperon, is a multi-baryon system with no charge. Studying the n n Λ state would provide information about the Λ n interaction which has not been directly measured by a scattering experiment. The experiment (E12-17-003) was performed in order to search for the n n Λ state at Jefferson Lab. The n n Λ is expected to be produced by the (e , e ′ K +) reaction, which has sensitivity to both bound and resonance states if the natural width of the n n Λ is narrow enough to be observed as a peak. The experiment used gas targets of hydrogen and tritium for mass calibration and the n n Λ production, respectively. The mass calibration with H (e , e ′ K +) Λ / Σ 0 reactions gave the mass resolution of the Λ and Σ 0 each 3.5 MeV / c 2 FWHM, for the elementary reaction. A spectrum of 3 H (e , e ′ K +) X was obtained, and a simple model with a Λ n final state interaction was applied to reproduce the spectrum. [ABSTRACT FROM AUTHOR]

Background: Adenocarcinoma of the esophagogastric junction (AEGJ) is most common in men and the elderly, but the disease is becoming more common in female and young adult persons. We have investigated the clinicoepidemiological characteristics of female and young adult patients with AEGJ and the 12-year trends in the Kurashiki area for young adult patients with AEGJ., Methods: Patients diagnosed with AEGJ in 12 hospitals between January 2008 and December 2019 were included in this study. Patients were divided into three groups by age (young adult [≤50 years], middle-aged [51 to 70 years], and elderly [>70 years]). Factors associated with AEGJ such as obesity, smoking, hiatal hernia and male, which were reported in our previous study, were identified., Results: One hundred and eighty-eight AEGJ patients, including 36 females and 20 young adults, were characterized. There was no significant change in the annual incidence of AEGJ among female (p=0.078) and young adult patients (p=0.89). Female patients without any associated factors, accounting for 53% (19/36) of the female patients and young adult patients, had significantly more histologically undifferentiated cancers than patients with at least one associated factor (58% [11/19] vs. 30% [50/169], p=0.025) and middle-aged and elderly patients (60% [12/20] vs. 30% [25/83] vs. 28% [24/85], p =0.026). Smoking was significantly less common in women than in men (8% [3/36] vs. 57% [87/152], p < 0.01). There were no significant differences between ages in the proportions of these associated factors., Conclusions: Histologically undifferentiated AEGJ cancers were more frequent in female patients without any associated factors and in young adult patients. Factors associated with AEGJ may differ between women and men, but they are similar in young adults and older adults. No increase in young adult patients with AEGJ was observed in the 12-year study., (© 2024. The Author(s).)

Scrotal masses, whether cystic or solid lesions, are routinely evaluated using ultrasonography. Magnetic resonance imaging (MRI) may be used for further investigation in cases with atypical findings, difficult diagnoses, large masses, and/or unclear relationships with the surrounding tissues. Scrotal solid masses are divided into intra- and extra-testicular masses. A staggering 90% of the intratesticular masses are malignant, whereas 75% of extratesticular masses are benign. Extratesticular masses are less common than intratesticular masses; however, some extratesticular masses present characteristic MRI findings. Familiarity with these specific MRI features of extratesticular masses is beneficial to radiologists, as appropriate diagnoses can help avoid unnecessary invasive treatments such as orchiectomy. In this review, we describe fibrous pseudotumors, polyorchidism, adenomatoid tumors, and scrotal leiomyoma as benign paratesticular masses, focusing on their characteristic imaging features on MRI. Although these tumors are extremely rare, their MRI findings are distinctive, and accurate diagnoses can prevent unnecessary orchiectomy. In addition, to demonstrate the pitfalls of diagnosing extratesticular masses, we present a case of seminoma misidentified as extratesticular masses due to large extensions outside the testis. Spermatic cord sarcoma, including rhabdomyosarcoma, leiomyosarcoma, and liposarcoma, and metastasis to the spermatic cord are described as malignant extratesticular masses. This review focused on extratesticular masses and elaborates the imaging findings that can aid in the accurate diagnosis using MRI., (© 2024. The Author(s).)

Background: Large non-apoptotic vesicles released from the plasma membrane protrusions are classified as large-EVs (LEVs). However, the triggers of LEV secretion and their functions in tumors remain unknown., Methods: Coculture system of cancer cells, peritoneal mesothelial cells (PMCs), and macrophages (MΦs) was conducted to observe cell-cell contact-mediated LEV secretion. Lineage tracing of PMCs was performed using Wt1 CreERT2 -tdT nu mice to explore the effects of LEVs on PMCs in vivo, and lymphangiogenesis was assessed by qRT-PCR and flow-cytometry., Results: In peritoneal dissemination, cancer cells expressing Ephrin-B (EFNB) secreted LEVs upon the contact with PMCs expressing ephrin type-B (EphB) receptors, which degraded mesothelial barrier by augmenting mesothelial-mesenchymal transition. LEVs were incorporated in subpleural MΦs, and these MΦs transdifferentiated into lymphatic endothelial cells (LEC) and integrated into the lymphatic vessels. LEC differentiation was also induced in PMCs by interacting with LEV-treated MΦs, which promoted lymphangiogenesis. Mechanistically, activation of RhoA-ROCK pathway through EFNB reverse signaling induced LEV secretion. EFNBs on LEVs activated EphB forward signaling in PMC and MΦs, activating Akt, ERK and TGF-β1 pathway, which were indispensable for causing MMT and LEC differentiation. LEVs accelerated peritoneal dissemination and lymphatic invasions by cancer cells. Blocking of EFNBs on LEVs using EphB-Fc-fusion protein attenuated these events., Conclusions: EFNB high cancer cells scattered LEVs when they attached to PMCs, which augmented the local reactions of PMC and MΦ (MMT and lymphangiogenesis) and exaggerated peritoneal dissemination., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: To evaluate the accuracy of combined imaging and blood test indices related to liver fibrosis (LF) compared to magnetic resonance elastography (MRE) for estimating severe LF (F3-4) in preoperative patients., Methods: This retrospective study included patients who underwent MRE, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI, and dynamic CT before liver resection. Liver stiffness measurement (LSM) using MRE, liver-to-spleen signal intensity ratio (LSR) using Gd-EOB-DTPA-enhanced MRI, and spleen volume normalized to body surface area (SV/BSA) using CT volumetry were measured. Laboratory parameters, including levels of type IV collagen 7S and hyaluronic acid, were also measured. Logistic regression and receiver operating characteristic analyses were performed to identify parameters that could estimate severe LF more accurately than LSM alone., Results: A total of 81 patients (mean age, 67 years ± 9.9 [SD]; 58 men) were enrolled. Multivariable logistic regression analysis indicated that LSR (odds ratio [OR]: 0.14, 95% confidence interval [CI]: 0.05-0.37, p < 0.001), SV/BSA (OR: 1.25, 95% CI: 1.02-1.52, p = 0.03) and type IV collagen 7S (OR: 1.84, 95% CI: 1.12-3.00, p = 0.02) were associated with severe LF. Receiver operating characteristic analysis showed that for estimating severe LF, the area under the curve was significantly larger for the combination of LSR, SV/BSA, and type IV collagen 7S than for LSM alone (0.95 vs 0.85, p = 0.04)., Conclusion: The combined evaluation of LSR, SV/BSA, and type IV collagen 7S obtained by clinically common preoperative examinations was more accurate than MRE alone for estimating severe LF in preoperative patients., Key Points: Question What indicators among the imaging and blood tests commonly performed preoperatively can provide a more accurate estimate of severe LF compared to MRE? Findings The combination of LSR, SV/BSA, and type IV collagen 7S was more accurate than an LSM alone for estimating severe LF. Clinical relevance A combination of commonly performed non-invasive preoperative tests provides a more accurate estimation of severe LF than MR elastography, an examination with relatively limited., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

We herein report a patient with Lynch-like syndrome in whom a brain tumor (glioblastoma) developed after repeated resection of colorectal cancer. The patient had a significant family history of cancer. Immunohistochemical expression of mismatch repair proteins was decreased in both brain and colon tumors, but no pathogenic variant of the related genes was detected. Although brain tumors occasionally develop in Lynch syndrome, they have not been reported in cases of Lynch-like syndrome. This first report of Lynch-like syndrome with the development of glioblastoma suggests the need for further investigation on the surveillance of brain tumors in patients with this syndrome.

Objective: Primary spinal cord gliomas are rare, and among these astrocytomas (WHO grade II) are much rarer. The optimal treatment strategy thus remains unclear. The authors conducted a multicenter study led by the Neurospinal Society of Japan (NSJ) to analyze treatment policies and outcomes. The aim was to present optimal treatment methods for spinal cord astrocytoma and to identify predictors of better outcomes., Methods: Among 1033 consecutive cases of spinal cord intramedullary tumors treated surgically at 58 centers affiliated with the NSJ, 57 patients were diagnosed with diffuse astrocytoma (WHO grade II) and were enrolled in the present study. Among these 57 patients, treatment methods, outcomes, and tumor proliferation rate as evaluated by the MIB-1 staining index (SI) were analyzed, and the optimal treatment method for spinal cord astrocytomas (grade II) was determined. In addition, the authors searched for factors predicting better treatment outcomes., Results: Treatment for spinal cord astrocytoma comprised three methods: surgery alone in 30 patients, adjuvant radiation therapy in 13 patients, and adjuvant chemoradiotherapy in 13 patients. One patient who did not undergo surgery was excluded from survival analysis. Treatment with surgery alone or surgery with radiotherapy was associated with significantly longer overall and progression-free survivals than that with adjuvant chemoradiotherapy. Patients treated with radiation therapy had a higher MIB-1 SI than those treated with surgery alone. The extent of tumor resection tended to correlate with longer survival. In contrast, postoperative neurological worsening showed the inverse order. Adjuvant chemoradiotherapy was associated with the shortest survival in both total cases and recurrent cases. The optimal cutoff value of MIB-1 SI for predicting longer survival by surgery alone was less than 4.0%., Conclusions: The optimal treatment for spinal cord astrocytoma is maximal tumor resection without neurological impairment. When some tumor remains in patients with an MIB-1 SI less than 4.0%, a wait-and-see approach is optimal. If the MIB-1 SI is higher than 4.0%, local radiation therapy is recommended. Adjuvant chemotherapy is not recommended for the treatment of grade II spinal cord astrocytoma.

A 24-year-old woman was referred to our hospital with joint pain, fever, abdominal pain, and diarrhea. A colonoscopy revealed longitudinal ulcers with a cobblestone appearance throughout the entire colon, suggestive of Crohn's disease. However, treatment with 5-aminosalicylic acid, azathioprine, and infliximab failed to achieve clinical remission. A colonoscopy 5 months later revealed a diffusely spreading granular mucosa without visible vasculature, compatible with active ulcerative colitis. Based on these serial changes in colonic lesions, we tested the patient for MEFV gene mutations and found variants E148Q and L110P in exon 2. Administration of colchicine resulted in complete clinical remission. Our experience suggests that drastic changes in the features of colonic inflammation may be a clue to the diagnosis of enterocolitis associated with familial Mediterranean fever., Competing Interests: Takayuki Matsumoto is a responsible and executive JGES member for DEN Open. The other authors declare no conflict of interest., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

C3 glomerulopathy is a rare disease that results in nephritis due to complement dysregulation and is characterized by C3 deposition in the glomerulus. Dysregulation of the alternative pathway underlies the pathogenesis, but activation of the terminal pathway is also common. The disease is often caused by acquired rather than genetic factors, i.e., autoantibodies against C3 or C5 converting enzyme (convertase) and other complement-related proteins. We report a case of C3 glomerulopathy diagnosed by renal biopsy that responded well to corticosteroids and went into complete remission within two months. Analysis of complements and complement-related proteins revealed a low level of C3 and a high level of soluble terminal pathway protein complex (sC5b-9). Under genetic analysis about complement-related genes, no pathogenic variant was observed. Based on these findings, we diagnosed this patient with C3 glomerulopathy with autoantibodies. Corticosteroids had a marked effect, which also supports this speculation. Analyses of complements and complement-related proteins, and genetic variants may be useful in understanding the pathogenesis of C3 glomerulopathy and in selecting treatment options., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Prognostic predictors of immunotherapy in patients with advanced endometrial cancer remain unclear. The potential role of inflammatory predictors, including pretreatment neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet scores, was investigated., Methods: Between August 2018 and December 2023, 35 patients were retrospectively analyzed. Prognostic predictors were compared, and optimal cut-off values that exhibited the greatest discrimination for overall response, disease control, progression-free survival and overall survival were determined. Multivariate analysis was used to assess the prognostic significance of the predictors., Results: The greatest discrimination for overall response, progression-free survival and overall survival included platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet; the areas under the curve were 0.638, 0.649 and 0.641, respectively. The precise cut-off values of neutrophil-to-lymphocyte ratio for progression-free survival and overall survival were 4.92 and 5.40, respectively. The lower neutrophil-to-lymphocyte ratio group had a significantly longer progression-free survival (P = 0.001, median survival; 4.0 months vs. 19 months) and longer overall survival (P = 0.002, median survival; 5.0 months vs. 21 months). Of the risk factors assessed, neutrophil-to-lymphocyte ratio (hazard ratio = 4.409; 95% CI = 1.10-17.64; P = 0.036) and regimen (hazard ratio = 5.559; 95% CI = 1.26-24.49; P = 0.023) were independently correlated with overall survival., Conclusion: In patients with advanced endometrial cancer, pretreatment neutrophil-to-lymphocyte ratio may be a prognostic predictor of those who would benefit from immunotherapy., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Lignin-carbohydrate complexes (LCCs) present a considerable hurdle to the economic utilization of lignocellulosic biomass. Glucuronoyl esterase (GE) is an LCC-degrading enzyme that catalyzes the cleavage of the cross-linkages between lignin and xylan in LCCs. Benzyl-d-glucuronate (Bn-GlcA), a commercially available substrate, is widely used to evaluate GE activity assays. However, since Bn-GlcA lacks the structural backbone of naturally occurring LCCs, the mechanisms underlying the activity of GEs and their diversity in the structure-activity relationship are not fully understood. Herein, we provided a synthesis scheme for designing 1,2 3 -α-d-(6-benzyl-4-O-methyl-glucuronyl)-1,4-β-d-xylotriose (Bn-MeGlcA 3 Xyl 3 ) as a natural core substrate bearing cross-linkage between lignin and glucuronoxylan. A well-defined and yet more realistic synthetic substrate was successfully synthesized via a key step of the benzyl esterification of 4-O-methyl-glucuronyl-1,4-β-d-xylotriose (MeGlcA 3 Xyl 3 ), a minimized fragment of glucuronoxylan enzymatically digested by β-1,4-xylanase. To the best of our knowledge, this is the first report of the productive GE kinetic analysis using this substrate. Kinetic parameters of the GE from the fungal Pestalotiopsis sp. AN-7 (PesGE), i.e., the K m , V max , and k cat of Bn-MeGlcA 3 Xyl 3 , were 0.43 mM, 55.5 μmol min -1 ·mg -1 , and 35.8 s -1 , respectively. On the other hand, as reported to date, the productive kinetic parameters for Bn-GlcA were not obtained because of its excessively high K m value (>16 mM). The substantial variance in the enzymatic activity of PesGE regarding substrate-binding affinity between Bn-MeGlcA 3 Xyl 3 and Bn-GlcA was also demonstrated using in silico docking simulation. These results suggested that the extended xylan fragment is a key structural determinant affecting PesGE's substrate recognition. Furthermore, the presence of a natural xylan backbone allows for evaluating the enzyme activity of xylan-degrading enzymes. Accordingly, the synthesized substrate with the natural core structure of LCC allowed us to unveil the productive kinetic parameters of GEs, serving as a versatile substrate for further elucidating the cascade reaction of GE and xylan-degrading enzymes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sangho Koh reports financial support was provided by Japan Society for the Promotion of Science. Sangho Koh reports financial support was provided by Shinshu UniversityJapan Society for the Promotion of Science. Masahiro Mizuno reports financial support was provided by Sugiyama Sangyou Kagaku Research Foundation. If there are other authors, they 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Sialyl glycans have several biological functions. We have previously reported on the preparation and bifidogenic activity of milk-derived sialylglycopeptide (MSGP) concentrate containing sialyl O -glycans. The current study qualitatively and quantitatively analyzed the sialyl O -glycans present in the MSGP concentrate. Notably, our quantitative analysis indicated that a majority of O -glycopeptides in the MSGP concentrate were derived from glycomacropeptides. The concentrate was found to contain mainly three types of sialyl core 1 O -glycans, with the disialyl core 1 O -glycan being the most abundant. We successfully quantified three types of sialyl core 1 O -glycans using a meticulous method that used homogeneous O -glycopeptides as calibration standards. Our results provide valuable insights into assessment strategies for the quality control of O -glycans in dietary products and underscore the potential applications of MSGP concentrate in the food industry and other industries.

Background: Sentinel lymph node navigation surgery, which identifies the sentinel lymph node in early cervical cancers and omits systemic pelvic lymphadenectomy in cases where no lymph node metastasis is present, has recently gained attention. However, there are few reports on lymph node recurrence and the long-term outcomes of cervical cancer surgery performed using sentinel lymph node navigation surgery. In this study, we aimed to evaluate the long-term outcomes of sentinel node navigation surgery for early-stage cervical cancer., Methods: One hundred thirty-eight patients with cervical cancer were enrolled. Sentinel lymph nodes were identified by injecting 99 m Technetium-labeled phytate and indocyanine green into the uterine cervix. Surgery and survival outcomes were also analyzed., Results: The median age and body mass index of the patients were 40 years (20-78) and 21.7 kg/m 2 (16.5-50.4), respectively. Open surgery, laparoscopic surgery, and robotic surgery were performed in 77 (56%), 53 (38%), and 8 (6%) patients, respectively. The overall and bilateral detection rates of the sentinel lymph node were 100% and 94%, respectively. Only one case (0.7%) exhibited lower extremity lymphedema, and pelvic lymphocele was observed in three cases (2.2%). Four cases (3%) experienced recurrence over a median follow-up of 57.5 months (range, 2-115 months), with five-year recurrence-free and overall survival rates of 97% and 97.3%, respectively., Conclusions: Our results demonstrate that sentinel node navigation surgery may be safe and effective for early-stage cervical cancer., (© 2024. The Author(s).)

Hepatic stellate cells (HSCs) are pericytes of the liver responsible for liver fibrosis and cirrhosis, which are the end stages of chronic liver diseases. TGF-β activates HSCs, leading to the differentiation of myofibroblasts in the process of liver fibrosis. While the heterogeneity of HSCs is appreciated in the fibrotic liver, it remains elusive which HSC subsets mainly contribute to fibrosis. Here, we show that the expression of the pericyte marker FoxD1 specifically marks a subset of HSCs in FoxD1-fate tracer mice. HSCs fate-mapped by FoxD1 were preferentially localized in the portal and peripheral areas of both the homeostatic and fibrotic liver induced by carbon tetrachloride. Furthermore, the deletion of Cbfβ, which is necessary for TGF-β signaling, in FoxD1-expressing cells ameliorated liver fibrosis. Thus, we identified an HSC subset that preferentially responds to liver injuries., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Peritoneal metastasis frequently accompanies metastatic and/or recurrent gastric cancer, leading to a poor prognosis owing to a lack of effective treatment. Hence, there is a pressing need to enhance our understanding of the mechanisms and molecules driving peritoneal metastasis. In a previous study, galectin-4 inhibition impeded peritoneal metastasis in a murine model. This study examined the glycan profiles of cell surface proteins and glycosphingolipids (GSLs) in cells with varying tumorigenic potentials to understand the intricate mechanisms underlying galectin-4-mediated regulation, particularly glycosylation. Detailed mass spectrometry analysis showed that galectin-4 knockout cells exhibit increased expression of lacto-series GSLs with β1,3-linked galactose while showing no significant alterations in neolacto-series GSLs. We conducted real-time polymerase chain reaction (PCR) analysis to identify candidate glycosyltransferases that synthesize increased levels of GSLs. Subsequently, we introduced the candidate B3GALT5 gene and selected the clones with high expression levels. B3GALT5 gene-expressing clones showed GSL glycan profiles like those of knockout cells and significantly reduced tumorigenic ability in mouse models. These clones exhibited diminished proliferative capacity and showed reduced expression of galectin-4 and activated AKT. Moreover, co-localization of galectin-4 with flotillin-2 (a raft marker) decreased in B3GALT5-expressing cells, implicating GSLs in galectin-4 localization to lipid rafts. D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (a GSL synthase inhibitor) also affected galectin-4 localization in rafts, suggesting the involvement of GSL microdomains. We discovered that B3GALT5 plays a crucial role in regulating peritoneal metastasis of malignant gastric cancer cells by suppressing cell proliferation and modulating lipid rafts and galectin-4 via mechanisms that are yet to be elucidated., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Coccidiosis caused by eimerian parasites results in lethal watery or bloody diarrhea in hosts, and markedly impairs the growth of and feed utilization by host animals. We previously investigated detailed the life cycle of Eimeria krijgsmanni as a mouse eimerian parasite. Only second-generation meronts, as an asexual stage, were morphologically detected in the epithelium of the host cecum for at least 8 weeks after infection, even though oocyst shedding finished approximately 3 weeks after infection. The presence of zoites was of interest because infection by eimerian parasites is considered to be self-limited after their patent period., Methods: To clarify the significance of residual second-generation meronts in E. krijgsmanni infection, we performed infection experiments using immunocompetent mice under artificial immunosuppression and congenital immunodeficient mice., Results: The number of oocysts discharged and the duration of oocyst discharge both increased in immunosuppressed mice. In immunodeficient mice, numerous oocysts were shed over a markedly longer period, and oocyst discharge did not finish until 56 days after inoculation., Conclusions: The present results suggest that the second-generation meronts survived in the epithelial cells of the cecum after the patent period, thereby contributing to extended infection as an asexual stage. The results obtained on E. krijgsmanni indicate that infections by Eimeria spp. are not self-limited and potentially continue for a long period of time., (© 2024. The Author(s).)

Frontal-striatal-thalamic circuit impairment is presumed to underlie schizophrenia. Individuals with attenuated psychosis syndrome (APS) show longitudinal volume reduction of the putamen in the striatum, which has a neural connection with the premotor cortex through the frontal-striatal-thalamic subcircuit. However, comprehensive investigations into the biological changes in the frontal-striatal-thalamic subcircuit originating from the premotor cortex in APS are lacking. We investigated differences in fractional anisotropy (FA) values between the striatum and premotor cortex (ST-PREM) and between the thalamus and premotor cortex (T-PREM) in individuals with APS and healthy controls, using a novel method TractSeg. Our study comprised 36 individuals with APS and 38 healthy controls. There was a significant difference between the control and APS groups in the right T-PREM (odds ratio = 1.76, p = 0.02). Other factors, such as age, sex, other values of FA, and antipsychotic medication, were not associated with differences between groups. However, while FA value reduction of ST-PREM and T-PREM in schizophrenia has been previously reported, in the present study on APS, the alteration of the FA value was limited to T-PREM in APS. This finding suggests that ST-PREM impairment is not predominant in APS but emerges in schizophrenia. Impairment of the neural network originating from the premotor cortex can lead to catatonia and aberrant mirror neuron networks that are presumed to provoke various psychotic symptoms of schizophrenia. Our findings highlight the potential role of changes in a segment of the frontal-thalamic pathway derived from the premotor cortex as a biological basis of APS., (© 2024. The Author(s).)

Osteoclasts are multinucleated bone-resorbing cells, and their formation is tightly regulated to prevent excessive bone loss. However, the mechanisms by which osteoclast formation is restricted remain incompletely determined. Here, we found that sterol regulatory element binding protein 2 (SREBP2) functions as a negative regulator of osteoclast formation and inflammatory bone loss. Cholesterols and SREBP2, a key transcription factor for cholesterol biosynthesis, increased in the late phase of osteoclastogenesis. The ablation of SREBP2 in myeloid cells resulted in increased in vivo and in vitro osteoclastogenesis, leading to low bone mass. Moreover, deletion of SREBP2 accelerated inflammatory bone destruction in murine inflammatory osteolysis and arthritis models. SREBP2-mediated regulation of osteoclastogenesis is independent of its canonical function in cholesterol biosynthesis but is mediated, in part, by its downstream target, interferon regulatory factor 7 (IRF7). Taken together, our study highlights a previously undescribed role of the SREBP2-IRF7 regulatory circuit as a negative feedback loop in osteoclast differentiation and represents a novel mechanism to restrain pathological bone destruction., (© 2024. The Author(s).)

Purpose: The correlation of cartilage thickness measured by three-dimensional (3D) magnetic resonance imaging (MRI) and the medial meniscal coverage ratio (MMCR), which presented pathology of the medial meniscus extrusion (MME) in 3D MRI, has not yet been elucidated. The study's purpose was to retrospectively verify whether the average cartilage thickness calculated by the automatic MRI 3D analysis system for each subregion was correlated with MMCR., Methods: A total of 60 patients underwent medial meniscus repair or high tibial osteotomy to treat their medial knee osteoarthritis. Cartilage thickness and MMCR were automatically calculated using 3D MRI software. The MMCR was defined as the ratio of the area covered by the meniscus within the medial tibial cartilage area to the total medial tibial cartilage area. The association between MMCR and the average cartilage thickness at 15 subregions in the medial femoral condyle (MFC) and medial tibial plateau (MTP) was evaluated using Spearman's rank correlation coefficient., Results: Kellgren-Lawrence grade exhibited a negative correlation with MMCR and a positive correlation with MME width. Cartilage thickness in the MTP had a moderately positive correlation with MMCR at four subregions and a weakly positive correlation at another subregion. Cartilage thickness in the MFC showed a moderately positive correlation with MMCR at five subregions and a weakly positive correlation at one subregion., Conclusions: Cartilage thickness calculated by automatic MRI 3D analysis system had a positive correlation with MMCR for all subregions of the anterior and middle subregions in the MFC and for five regions of nine subregions of the anterior and middle subregions in the MTP., Level of Evidence: Level II, cross-sectional study (diagnosis)., Competing Interests: Ichiro Sekiya has funding from FUJIFILM Corporation. The authors declare no conflicts of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background: Peritoneal metastasis of gastric cancer is closely associated with dismal prognosis. In previous preclinical proof-of-concept studies, an amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotide (ASO), designated ASO-4733 that targets the gene encoding synaptotagmin XIII (SYT13), inhibited cellular functions required for the formation of peritoneal metastasis of gastric cancer cells. ASO-4733 achieved therapeutic effects when intra-abdominally administered to mouse xenograft models. Here, we conducted an analysis of Syt13-deficient mice to determine the pharmacokinetics and toxicity of intra-abdominal administration of ASO-4733., Methods: The effects of Syt13-deficiency in mice were determined. Good Laboratory Practice toxicity tests and the toxicokinetics of intra-abdominal administration of ASO-4733 were conducted in cynomolgus monkeys and rats. The pharmacokinetics of ASO-4733 administered intravenously or intra-abdominally to rats were investigated., Results: Syt13-deficient mice exhibited normal reproduction, organ functions, and motor functions. Weekly intra-abdominal administration of ASO-4733 (125 mg/kg), corresponding to a 50-fold increase of the estimated clinical dose for 4 weeks, was well tolerated by cynomolgus monkeys. In rats, off-target toxicity (not attributable to hybridization) was observed after weekly intra-abdominal administration of ASO-4733. Blood concentrations of ASO-4733 were lower and rose more slowly after intra-abdominal administration compared with intravenous administration., Conclusions: The preclinical profile of intra-abdominal administration of ASO-4733 demonstrated its suitability for entry into clinical trials of patients with peritoneal metastasis of gastric cancer., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

The exercise pressor reflex (EPR) is exaggerated in type 2 diabetes mellitus (T2DM), but the underlying central nervous system aberrations have not been fully delineated. Stimulation of muscle afferents within working skeletal muscle activates the EPR, by sending information to neurons in the brainstem, where it is integrated and results in reflexively increased mean arterial pressure (MAP) and sympathetic nerve activity. Brain insulin is known to regulate neural activity within the brainstem. We hypothesize that brain insulin injection in T2DM rats attenuates the augmented EPR, and that T2DM is associated with decreased brain insulin. Using male Sprague-Dawley rats, T2DM and control rats were generated via an induction protocol with two low doses of streptozotocin (35 and 25 mg/kg, i.p.) in combination with a 14-23-week high-fat diet or saline injections and a low-fat diet, respectively. After decerebration, MAP and renal sympathetic nerve activity (RSNA) were evaluated during EPR stimulation, evoked by electrically induced muscle contraction via ventral root stimulation, before and after (1 and 2 h post) intracerebroventricular (i.c.v.) insulin microinjections (500 mU, 50 nl). i.c.v. insulin decreased peak MAP (ΔMAP Pre (36 ± 14 mmHg) vs. 1 h (21 ± 14 mmHg) vs. 2 h (11 ± 6 mmHg), P < 0.05) and RSNA (ΔRSNA Pre (107.5 ± 40%), vs. 1 h (75.4 ± 46%) vs. 2 h (51 ± 35%), P < 0.05) responses in T2DM, but not controls. In T2DM rats, cerebrospinal fluid insulin was decreased (0.41 ± 0.19 vs. 0.11 ± 0.05 ng/ml, control (n = 14) vs. T2DM (n = 4), P < 0.01). The results demonstrated that insulin injections into the brain normalized the augmented EPR in brain hypoinsulinaemic T2DM rats, indicating that the EPR can be regulated by brain insulin. KEY POINTS: The reflexive increase in blood pressure and sympathetic nerve activity mediated by the autonomic nervous system during muscle contractions is also known as the exercise pressor reflex. The exercise pressor reflex is dangerously augmented in type 2 diabetes, in both rats and humans. In type 2 diabetic rats both cerebrospinal fluid insulin and phosphoinositide 3-kinase signalling within cardiovascular brainstem neurons decrease in parallel. Brain insulin injections decrease the magnitude of the reflexive pressor and sympathetic responses to hindlimb muscle contraction in type 2 diabetic rats. Partial correction of low insulin within the central nervous system in type 2 diabetes may treat aberrant exercise pressor reflex function., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

A Schiff base in the retinal chromophore of microbial rhodopsin is crucial to its ion transport mechanism. Here, we discovered an unprecedented isotope effect on the C═N stretching frequency of the Schiff base in sodium ion-pumping rhodopsins, showing an unusual interaction of the Schiff base. No amino acid residue attributable to the unprecedented isotope effect was identified, suggesting that the H-O-H bending vibration of a water molecule near the Schiff base was coupled with the C═N stretching vibration. A twist in the polyene chain in the chromophore for the sodium ion-pumping rhodopsins enabled this unusual interaction of the Schiff base. The present discovery provides new insights into the interaction network of the retinal chromophore in microbial rhodopsins.

Chiral molecular assemblies have attracted considerable attention because of their interesting physical properties, such as spin-selective electron transport. Cation-anion salts of three azolium cations, imidazolium ( HIm + ), triazolium ( HTrz + ), and thiazolium ( HThz + ), in combination with a chiral camphorsulfonate (1 S - CS - ) and their racemic compounds ( rac - CS - ) were prepared and compared in terms of phase transitions, crystal structures, dynamics of constituent molecules, dielectric responses, and proton conductivities. The cation-anion crystals containing HIm + showed no significant difference in proton conductivity between the homochiral and racemic crystals, whereas the HTrz + -containing crystals showed higher proton conductivity and lower activation energy in the homochiral form than in the racemic form. A two-dimensional hydrogen-bonding network consisting of HTrz + and -SO 3 - groups and similar in-plane rotational motion was observed in both crystals; however, the HTrz + cation in the homochiral crystal exhibited the rotational motion modulated with translational motion, whereas the HTrz + cation in the racemic crystal exhibited almost steady in-plane rotational motion. The different motional degrees of freedom were confirmed by crystal structure analyses and temperature- and frequency-dependent dielectric constants. In contrast, steady in-plane rotational motion with the thermally activated fluctuating motion of CS - was observed both in homochiral and racemic crystals containing HIm + , which averaged the motional space of protons resulting in similar dielectric responses and proton conductivities. The control of motional degrees of freedom in homochiral crystals affects the proton conductivity and is useful for the design of molecular proton conductors.

Adipocyte-cancer cell interactions promote tumor development and progression. Previously, we identified adipsin (CFD) and its downstream effector, hepatocyte growth factor (HGF), as adipokines that enhance adipocyte-breast cancer stem cell interactions. Here, we show that adipsin-dependent adipocyte maturation and the subsequent upregulation of HGF promote tumor invasion in breast cancers. Mature adipocytes, but not their precursors, significantly induced breast tumor cell migration and invasion in an adipsin expression-dependent manner. Promoters of tumor invasion, galectin 7 and matrix metalloproteinases, were significantly upregulated in cancer cells cocultured with mature adipocytes; meanwhile, their expression levels in cancer cells cocultured with adipocytes were reduced by adipsin knockout (Cfd KO) or a competitive inhibitor of CFD. Tumor growth and distant metastasis of mammary cancer cells were significantly suppressed when syngeneic mammary cancer cells were transplanted into Cfd KO mice. Histological analyses revealed reductions in capsular formation and tumor invasion at the cancer-adipocyte interface in the mammary tumors formed in Cfd KO mice. These findings indicate that adipsin-dependent adipocyte maturation may play an important role in adipocyte-cancer cell interaction and breast cancer progression., (© 2024. The Author(s).)

Hemoglobins achieve cooperative oxygen binding by diverse strategies based on different assemblies of globin subunits. Heterotetrameric hemoglobin from Scapharca inaequivalvis (HbII) consists of two AB-dimers, whose structure closely resembles that of homodimeric hemoglobin from the same organism (HbI). Herein, we investigated the structural dynamics of HbII following carbon monoxide (CO) dissociation using time-resolved resonance Raman (RR) spectroscopy. The observed spectra showed that the heme structure of the transient dissociated form of HbII was similar to that of HbI; however, the transition from the transient dissociated form to the equilibrium unligated form was faster for HbII than for HbI. Furthermore, the dependence of the time-resolved spectra on the yield of CO dissociation revealed that the transition became faster as the number of dissociated ligands increased from one to four. The positive correlation between the rate constants and number of dissociated ligands indicates that the structural transition of HbII following CO dissociation is cooperative.

The characteristic feature of chronic peritoneal damage in peritoneal dialysis (PD) is a decline in ultrafiltration capacity associated with pathological fibrosis and angiogenesis. The pathogenesis of peritoneal fibrosis is attributed to bioincompatible factors of PD fluid and peritonitis. Uremia is associated with peritoneal membrane inflammation that affects fibrosis, neoangiogenesis, and baseline peritoneal membrane function. Net ultrafiltration volume is affected by capillary surface area, vasculopathy, peritoneal fibrosis, and lymphangiogenesis. Many inflammatory cytokines induce fibrogenic growth factors, with crosstalk between macrophages and fibroblasts. Transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF)-A are the key mediators of fibrosis and angiogenesis, respectively. Bioincompatible factors of PD fluid upregulate TGF-β expression by mesothelial cells that contributes to the development of fibrosis. Angiogenesis and lymphangiogenesis can progress during fibrosis via TGF-β-VEGF-A/C pathways. Complement activation occurs in fungal peritonitis and progresses insidiously during PD. Analyses of the human peritoneal membrane have clarified the mechanisms by which encapsulating peritoneal sclerosis develops. Different effects of dialysates on the peritoneal membrane were also recognized, particularly in terms of vascular damage. Understanding the pathophysiologies of the peritoneal membrane will lead to preservation of peritoneal membrane function and improvements in technical survival, mortality, and quality of life for PD patients.

Background: The Kidney Disease Improving Global Outcomes guidelines recommend nephrology referral for patients with chronic kidney disease (CKD) stages 4 to 5, significant proteinuria and persistent microscopic haematuria. However, the recommendations are opinion-based and which patients with CKD benefit more from nephrology referral has not been elucidated., Methods: In this retrospective cohort study, patients referred to our nephrology outpatient clinic from April 2017 to March 2019 were included. We excluded patients considered to have an acute decline in kidney function (annual decline in estimated glomerular filtration rate [eGFR] >10 mL/min/1.73 m 2 ). The slopes of eGFR before and after nephrology referral were estimated and compared by linear mixed effects models. Interaction between time and referral status (before or after referral) was assessed and effect modifications by the presence of diabetes, proteinuria (defined by urine dipstick protein 2+ or more), urine occult blood, hypoalbuminemia (defined by albumin levels less than 3.5 g/dL) and anaemia (defined by haemoglobin levels less than 11.0 g/dL) were evaluated., Results: The eGFR slope significantly improved from -2.05 (-2.39 to -1.72) to -0.96 (-1.36 to -0.56) mL/min/1.73 m 2 /year after nephrology referral (p < .001). The improvement in eGFR slope was more prominent among those with diabetes mellitus, anaemia, and hypoalbuminemia (all p-values for three-way interaction <.001 after adjustment for covariates). Further adjustments for time-dependent haemoglobin levels, the use of erythropoiesis-stimulating agents, iron supplementation, anti-hypertensives and anti-diabetic medications did not change the significance of the interactions., Conclusions: Nephrology referral slows CKD progression, especially among those with hypoalbuminemia, diabetes or anaemia. Patients with hypoalbuminemia, diabetes or anaemia might benefit more from specialized care and lifestyle modifications by nephrologists. The inclusion of anaemia and hypoalbuminemia in nephrology referral criteria should be considered., (© 2024 Asian Pacific Society of Nephrology.)

Purpose: The correlation between cartilage thickness evaluated by 3D MRI and knee alignment has not been elucidated. The study's purpose was to retrospectively verify whether average cartilage thickness calculated by the automatic MRI 3D analysis system for each subregion was correlated with knee alignment., Methods: A total of 53 patients underwent medial meniscus repair or high tibial osteotomy for medial knee osteoarthritis. Cartilage thickness was automatically calculated using 3D MRI software. Knee alignment, weight-bearing line ratio (WBLR), joint line convergence angle (JLCA), medial proximal tibial angle (MPTA), and lateral distal femoral angle (LDFA) were calculated on a weight-bearing long-leg radiograph using digital planning software. The association between knee alignment and the average cartilage thickness at 18 subregions in the medial femoral condyle (MFC) and medial tibial plateau (MTP) was evaluated using Spearman's rank correlation coefficient., Results: Cartilage thickness of the MFC had moderately positive correlations with WBLR at four subregions and weak correlations at two subregions. Cartilage thickness of the MTP had moderately positive correlations with WBLR at four subregions. Cartilage thickness of the MFC had moderately negative correlations with JLCA at six subregions. Cartilage thickness of the MTP had moderately negative correlations with JLCA at four subregions and a weak correlation at one subregion. Conversely, cartilage thickness had weak correlations with MPTA or LDFA., Conclusions: In knees with pathological conditions in the medial compartment, cartilage thicknesses by 3D MRI had positive correlations with WBLR and JLCA at almost all subregions of the MFC and at the anterior-middle and central-external of the MTP. Treatment strategies should be considered in light of these regions., Level of Evidence: Cross-sectional study (diagnosis); Level of evidence, 2., Competing Interests: Declaration of competing interest FUJIFILM Corporation. The corresponding author received the funding from FUJIFILM corporation., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Although exploratory laparoscopy in patients with advanced ovarian cancer is a diagnostic tool for determining treatment strategy, its safety has not been completely investigated. We report a case involving a severe abdominal abscess following an exploratory laparoscopy. A 65-year-old woman with advanced ovarian cancer developed a large abdominal abscess following exploratory laparoscopy and neoadjuvant chemotherapy. Emergent laparotomy was performed; while massive bowel adhesion surrounding the abscess did not allow for genital organ resection, an incision in the left port area was made to drain the abscess. The patient's chemotherapy was delayed because she experienced sub-ileus, postoperatively. Only a limited number of studies have been conducted on the safety of these techniques. This intense infection case emphasizes the need for further investigations into the safety of exploratory laparoscopy in patients with progressive diseases under heterogeneous conditions in real-world settings., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of the Institutional Review Board of Kagoshima University Graduate School of Medical Sciences issued approval 230340. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Fukunishi et al.)

Introduction: Cell-processing facilities face the risk of environmental bacteria contaminating biosafety cabinets during processing, and manual handling of autologous cell products can result in contamination. We propose a risk- and evidence-based cleaning method for cross-contamination, emphasizing proteins and DNA., Methods: The transition and residual risks of the culture medium were assessed by measuring both wet and dried media using fluorescence intensity. Residual proteins and DNA in dried culture medium containing HT-1080 cells were analyzed following ultraviolet (UV) irradiation, wiping, and disinfectant treatment., Results: Wet conditions showed a higher transition to distilled water (DW), whereas dry conditions led to higher residual amounts on SUS304 plates. Various cleaning methods for residual culture medium were examined, including benzalkonium chloride with a corrosion inhibitor (BKC + I) and DW wiping, which demonstrated significantly lower residual protein and DNA compared to other methods. Furthermore, these cleaning methods were tested for residual medium containing cells, with BKC + I and DW wiping resulting in an undetectable number of cells. However, in some instances, proteins and DNA remained., Conclusions: The study compared cleaning methods for proteins and DNA in cell products, revealing their advantages and disadvantages. Peracetic acid (PAA) proved effective for nucleic acids but not proteins, while UV irradiation was ineffective against both proteins and DNA. Wiping emerged as the most effective method, even though traceability remained challenging. However, wiping with ETH was not effective as it caused protein immobilization. Understanding the characteristics of these cleaning methods is crucial for developing effective contamination control strategies., Competing Interests: The authors declare the following financial interests/personal relationships that may be considered potential competing interests: Mitsuru Mizuno reports the financial support provided by Terumo Corporation., (© 2024 The Author(s).)

Neutrophil extracellular trap (NET) formation is a unique self-defense mechanism of neutrophils; however, it is also involved in many diseases, including atherosclerosis. Resveratrol and catechin are antioxidants with anti-atherosclerotic properties. Here, we examined the effects of resveratrol, catechin, and other related compounds on NET formation. HL-60-derived neutrophils were pretreated with resveratrol and other compounds before stimulation with phorbol-myristate acetate (PMA). DNA and myeloperoxidase released from neutrophils were determined. Resveratrol suppressed the DNA release from neutrophils in a dose-dependent manner. NET formation was enhanced by 1-palmitoyl-2-oxovaleroyl phosphatidylcholine (POVPC), a truncated form of oxidized phospholipid, and resveratrol suppressed NET formation induced by POVPC and PMA. Furthermore, we designed several analogs of resveratrol or catechin whose conformation was restricted by the inhibition of the free rotation of aromatic rings. The conformationally constrained analogs were more effective at inhibiting NET formation; however, their inhibitory function decreased when compound was a large, hydrophobic analog. The most potent compounds, planar catechin and resveratrol, suppressed myeloperoxidase release from activated neutrophils. In addition, these compounds suppressed DNA release from neutrophils stimulated with calcium ionophore. These results suggest that resveratrol, catechin and their analogs exert anti-NET effects, and that constraining the geometry of these compounds enhanced their inhibitory effects., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2024 JCBN.)

In this study, we developed and demonstrated a millimeter-wave electric field imaging system using an electro-optic crystal and a highly sensitive polarization measurement technique using a polarization image sensor, which was fabricated using a 0.35-µm standard CMOS process. The polarization image sensor was equipped with differential amplifiers that amplified the difference between the 0° and 90° pixels. With the amplifier, the signal-to-noise ratio at low incident light levels was improved. Also, an optical modulator and a semiconductor optical amplifier were used to generate an optical local oscillator (LO) signal with a high modulation accuracy and sufficient optical intensity. By combining the amplified LO signal and a highly sensitive polarization imaging system, we successfully performed millimeter-wave electric field imaging with a spatial resolution of 30×60 µm at a rate of 1 FPS, corresponding to 2400 pixels/s.

Serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesions (STILs), and the p53 signature are considered to be related to precursor lesions of high-grade serous carcinomas (HGSCs). However, the clinical significance and prognostic implications of these lesion types are currently unknown. We diagnosed three patients with STILs according to the morphological evaluation criteria and combined this with p53 and Ki-67 immunostaining. One patient had an HGSC of the ovary that was incidentally discovered at the time of ovarian cyst resection, and the HGSC in the other two patients was characterized after they underwent risk-reducing salpingo-oophorectomy. Herein, we present a report of three patients with STILs diagnosed based on clinical data and pathological findings, along with a review of the literature., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mizuno et al.)

Prosopagnosia is a cognitive disorder in which facial recognition is severely impaired despite normal vision and intelligence. Prosopagnosia was first reported in the 1800s, but its cause remains unclear. Although other neurological symptoms are often present, some patients have pure prosopagnosia. The bilateral occipital lobes are believed to be associated with symptoms. Recent brain imaging techniques have identified the right fusiform gyrus (rFG), located at the junction of the right occipital temporal lobe, as the affected region. In this report, we present a case of associative prosopagnosia with no concomitant symptoms in a 76-year-old man. Brain magnetic resonance imaging detected a subcortical hemorrhage in the right temporal lobe. Using tractography based on diffusion tensor imaging, we visualized atrophy of the right inferior longitudinal fasciculus (ILF). This is the first time tractography has been used to show a clear association between associative prosopagnosia and ILF damage projecting from the rFG.