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Taisuke Ezaki,1 Hiroshi Hongo,1 Kimiharu Takamatsu,1 Nobuyuki Tanaka,2 Mototsugu Oya2 1Department of Urology, Nerima General Hospital, Tokyo, Japan; 2Department of Urology, Keio University School of Medicine, Tokyo, JapanCorrespondence: Taisuke Ezaki, Department of Urology, Nerima General Hospital, 1-24-1 Asahigaoka, Nerima-Ku, Tokyo, 176-8530, Japan, Tel +81-3-5988-2200, Fax +81-3-5988-2250, Email tezaki@nerima-hosp.or.jpPurpose: Contact laser vaporization of the prostate (CVP) for benign prostatic hyperplasia is a widely accepted and safe procedure for elderly patients because of its lower bleeding risks. However, CVP lacks a postoperative pathological examination for prostate cancer. Concomitant prostate biopsy and CVP may complement this disadvantage; however, the risk of bleeding associated with this procedure remains unclear. This study aimed to evaluate the safety of a concomitant prostate biopsy and CVP.Patients and Methods: This retrospective study included 106 men who had undergone CVP in Nerima General Hospital. Prostate biopsies and CVP were performed simultaneously on 16 patients. We defined the “hemorrhage group” by a > 5% decrease in hemoglobin the day after surgery. Preoperative and operative indices were evaluated based on the association with the hemorrhage group.Results: Participants in the concomitant biopsy group were older (p = 0.001), had larger prostates (p = 0.014), a lower rate of prostate biopsy history (p = 0.046), longer postoperative urinary catheter duration (p = 0.024), and a higher rate of decline in hemoglobin levels the day after surgery (p = 0.023). Patients in the hemorrhage group (n = 20, 18.9%) showed a significantly higher rate of concomitant biopsy and CVP (p = 0.006). Multivariate analysis showed that concomitant prostate biopsy (p = 0.009, odds ratio = 4.61) was the sole statistically significant predictive factor for hemorrhage.Conclusion: Concomitant prostate biopsy and CVP of the prostate may increase the risk of bleeding.Keywords: benign prostatic hyperplasia, contact laser vaporization of the prostate, diode laser, prostate biopsy, vaporization

Single-walled carbon nanotubes (SWCNTs) exhibit p-type properties in air, necessitating electron doping using n-dopants (e.g., reducing agents) for the development of SWCNT-based electronic devices. Dimethylbenzimidazole (DMBI-H) derivatives serve as effective electron dopants, not only for SWCNTs, but also for various organic semiconducting materials. However, the doping reaction is still a subject of debate. In this study, the electron-doping reactions of ortho-methoxy-substituted DMBI-H for SWCNTs were analyzed in protic and aprotic solvents in the presence and absence of dioxygen (O2). The presence of O2 was found to cause the reduction of O2 on the SWCNT surface in the protic solvent, resulting in the production of DMBI cations and water through proton-coupled electron transfer (PCET) from the n-doped SWCNT and ethanol. This work elucidates the mechanism behind the air-stability of n-type SWCNTs. [ABSTRACT FROM AUTHOR]

Background/aim: Radiotherapy is one of the most frequently used options for prostate cancer (PCa). However, adverse effects related to irradiation of surrounding normal organs are significant clinical concerns. Specifically, genitourinary toxicity can dramatically reduce the quality of life. This clinical trial investigated the efficacy of oral 5-aminolevulinic acid phosphate combined with sodium ferrous citrate (ALA-SFC) in patients treated with low-dose-rate brachytherapy (LDR-BT) using an iodine-125 seed source., Patients and Methods: The AMBER study was a prospective single-center trial involving patients with localized PCa who underwent LDR-BT without external-beam radiotherapy (jRCTs051190077). Fifty patients were included and instructed to take capsules of ALA-SFC twice a day (200 mg phosphate salt and 229.42 mg per day) for six months from the day of seed implantation (prescribed radiation dose of 160 Gy). Patient data were collected before implantation, during ALA-SFC treatment, and at 1, 3, 6, 9, and 12 months post-LDR-BT. The primary endpoint of this trial was urinary frequency at three months. Other patient-reported outcomes, investigator-reported adverse events, and oncological outcomes were secondary endpoints., Results: Of 50 enrolled cases (45 in the per-protocol analysis, 49 in the safety analysis), urinary frequency and its increase from baseline did not differ from 141 historical controls at any time point, including at three months post-LDR-BT. Propensity score matched analysis confirmed no time-course differences in frequency, volume, or urinary symptom scores between groups. Biochemical failure-free and metastasis-free survival also remained similar., Conclusion: Oral supplementation of ALA-SFC to LDR-BT did not alleviate radiation-induced toxicity or improve oncological outcomes., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To evaluate the difficulty of laparoscopic adrenalectomy by investigating the usefulness of the Mayo Adhesive Probability (MAP) score for assessing adherent perinephric fat and its correlation with histological reality., Patients and Methods: We retrospectively evaluated 103 patients who underwent laparoscopic adrenalectomies. Based on preoperative computed tomography images, the patients were categorized into two groups: high (3-5 points) and low MAP (0-2 points). Clinical characteristics and perioperative data were compared between the two groups. Additionally, we analyzed the pathological tissue of the tumor and surrounding fat using hematoxylin-eosin-saffron staining., Results: Compared with the low MAP group, the high MAP group had younger patients (59 vs. 62 years, p=0.097), more male patients (93.3% vs. 44.3%, p<0.001), and higher body mass indices (26.4 vs. 23.8, kg/m 2 , p=0.029). The MAP group experienced a significantly higher estimated blood loss compared to the low MAP group (10 vs. 52.3, ml, p=0.047). Tumor and adhering perirenal fat tissues of pheochromocytoma, adrenal carcinoma, and metastatic adrenal tumors exhibited significantly higher expression of vascular endothelial growth factor and cluster of differentiation 204 compared to the low MAP group (p<0.001). Additionally, both proteins were highly expressed in the adhering perirenal fat in the high MAP group (p=0.020, p=0.015)., Conclusion: Patients with a preoperative MAP score ≥3, pheochromocytoma, or malignant tumor had a high risk of increased intraoperative blood loss. Strict perioperative management should be performed in such cases., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Anesthesiology departments and professional organizations increasingly recognize the need to embrace diverse membership to effectively care for patients, to educate our trainees, and to contribute to innovative research. 1 Bibliometric analysis uses citation data to determine the patterns of interrelatedness within a scientific community. Social network analysis examines these patterns to elucidate the network's functional properties. Using these methodologies, an analysis of contemporary scholarly work was undertaken to outline network structure and function, with particular focus on the equity of node and graph-level connectivity patterns., Methods: Using the Web of Science, this study examines bibliographic data from 6 anesthesiology-specific journals between January 1, 2017, and August 26, 2022. The final data represent 4453 articles, 19,916 independent authors, and 4436 institutions. Analysis of coauthorship was performed using R libraries software. Collaboration patterns were assessed at the node and graph level to analyze patterns of coauthorship. Influential authors and institutions were identified using centrality metrics; author influence was also cataloged by the number of publications and highly cited papers. Independent assessors reviewed influential author photographs to classify race and gender. The Gini coefficient was applied to examine dispersion of influence across nodes. Pearson correlations were used to investigate the relationship between centrality metrics, number of publications, and National Institutes of Health (NIH) funding., Results: The modularity of the author network is significantly higher than would be predicted by chance (0.886 vs random network mean 0.340, P < .01), signifying strong community formation. The Gini coefficient indicates inequity across both author and institution centrality metrics, representing moderate to high disparity in node influence. Identifying the top 30 authors by centrality metrics, number of published and highly cited papers, 79.0% were categorized as male; 68.1% of authors were classified as White (non-Latino) and 24.6% Asian., Conclusions: The highly modular network structure indicates dense author communities. Extracommunity cooperation is limited, previously demonstrated to negatively impact novel scientific work. 2 , 3 Inequitable node influence is seen at both author and institution level, notably an imbalance of information transfer and disparity in connectivity patterns. There is an association between network influence, article publication (authors), and NIH funding (institutions). Female and minority authors are inequitably represented among the most influential authors. This baseline bibliometric analysis provides an opportunity to direct future network connections to more inclusively share information and integrate diverse perspectives, properties associated with increased academic productivity. 3 , 4., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Thrombospondin 2 (TSP2) plays a vital role in collagen/fibrin formation, bone growth, vascular density regulation, hemostasis, and cell adhesion. Close associations of serum TSP2 with histological severity in non-alcoholic fatty liver disease and chronic hepatitis C were reported. The present study investigated the significance of circulating TSP2 in chronic hepatitis B patients. Eighty-seven biopsy-proven chronic hepatitis B patients were analyzed in cross-sectional Study 1 to search for correlations between serum TSP2 levels prior to liver biopsy and clinicopathological parameters. In longitudinal Study 2, 51 chronic hepatitis B patients with long-term follow-up (mean: 7.5 years) were examined for changes in serum TSP2 levels during nucleos(t)ide analog (NA) therapy along with trends in hepatocarciongenesis. In Study 1, serum TSP2 levels were not significantly associated with portal inflammation or fibrosis. Study 2 revealed that serum TSP2 was significantly decreased after 48 weeks of NA therapy (P < 0.001). Notably, TSP2 levels at 48 weeks of NA administration (TSP2-48W) were significantly higher in the hepatocellular carcinoma (HCC) (+) group than in the HCC (-) group (P = 0.043). Kaplan-Meier analysis showed that higher TSP2-48W (≥ 24 ng/mL) was associated with future HCC development (P = 0.030). Serum TSP2 levels may be a potential predictor of HCC development in hepatitis B patients receiving NA therapy. Longitudinal prospective studies are necessary to validate our findings., (© 2024. The Author(s).)

Introduction: This multicenter study aimed to determine whether the pretreatment prognostic nutrition index (PNI) or a change in the index after two treatment courses could be a biomarker for predicting treatment sensitivity in patients with unresectable advanced or recurrent gastric cancer (GC) treated using chemotherapy and nivolumab as the first-line treatment., Methods: This multicenter retrospective study with 104 patients was conducted at 12 institutions. PNI was calculated before treatment and after two courses of treatment in each case. We also focused on changes in PNI from the pretreatment value., Results: After two courses of chemotherapy plus nivolumab treatment, the high PNI group had significantly better rates of overall survival (OS) (p = 0.0016) and time to treatment failure (p = 0.0060). Low PNI was an independent prognostic factor predicting both therapeutic sensitivity to chemotherapy plus nivolumab treatment and poorer OS. Furthermore, correlation with low pretreatment PNI transitioning to high after two courses of treatment was not noted in any patient in the progressive disease group (p = 0.0075)., Conclusions: PNI is a score composed of a patient's albumin level and lymphocyte count that can be easily assessed in daily clinical practice. Evaluating it is easy for each treatment; thus, when there is a focus on its transition, PNI could be a very powerful biomarker for predicting treatment sensitivity., (S. Karger AG, Basel.)

While Mn 2+ ions are well-established for reducing the fidelity of DNA polymerases, leading to the misincorporation of nucleotides, our investigation of the effects of metal ions revealed a contrasting role of Zn 2+ . Here, we demonstrate that Zn 2+ ions enhance the fidelity of DNA polymerases (the 3' → 5' exonuclease-deficient Klenow fragment and Taq DNA polymerase) by suppressing misincorporation during primer extension reactions. Remarkably, Zn 2+ ions inhibit both intrinsic misincorporation and Mn 2+ -induced misincorporation of nucleotides. Furthermore, Zn 2+ ions also effectively suppressed misincorporation during metal-mediated primer extension reactions, which involved forming Ag + and Hg 2+ ion-mediated base pairs. These findings suggest that Zn 2+ ions inhibit both intrinsic and Mn 2+ -induced mismatched base pair formation. Consequently, the combined use of Mn 2+ and Zn 2+ ions may offer a strategy for precisely regulating the fidelity of DNA polymerases. Remarkably, Zn 2+ ions even suppress misincorporation in primer extension reactions that rely on metal-mediated base pairs, and conversely, this suggests that DNA polymerases recognize metal-mediated base pairs such as T-Hg 2+ -T, C-Ag + -A, and C-Ag + -T as relatively stable base pairs. These results imply that Zn 2+ ions may also enhance the fidelity of DNA polymerases when incorporating non-canonical nucleobases, potentially paving the way for the expansion of the genetic alphabet.

Phytochemical investigation on the aerial parts of Lysionotus pauciflorus Maxim. (Gesneriaceae), a medicinal plant used in Guangxi Zhuang Autonomous Region, China, resulted in the isolation of 13 secondary metabolites including two methoxyflavones, six flavonoid glycosides, and five caffeoyl phenylethanoid glycosides. Among these, the chemical structures of previously undescribed metabolites (1-3) were elucidated to be nevadensin 7-O-β-D-glucopyranosyl-(1 → 2)-β-D-glucopyranoside (1), nevadensin 7-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2), and 2-(3,4-dihydroxyphenyl)ethyl-1-O-β-D-apiofuranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 3)-β-D-(6'-O-E-caffeoyl)glucopyranoside (3) by detailed spectroscopic and HPLC analyses. Inhibitory activity of isolated compounds against RSL3-induced ferroptosis on human hepatoma Hep3B cells were evaluated., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

This multicentre study investigated the dynamics of thrombospondin 2 (TSP2) levels during direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV) infected patients and evaluated TSP2's potential as a predictive marker for hepatocellular carcinoma (HCC). All 134 participants achieved sustained virological response at 12 weeks (SVR12) with DAA therapy, and serum TSP2 levels significantly decreased from before and after treatment (p < 0.001). During the median follow-up period of 6.0 years, HCC after DAA therapy was observed in 16 patients (11.9%). Patients with serum TSP2 High (≥ 32 ng/mL) at SVR12 had a significantly higher cumulative occurrence of HCC than did those without (26.5% vs. 7.0%, p = 0.0033). A multivariate Cox proportional hazards model identified male gender (HR 4.84, p = 0.005), HCC history (HR 4.61, p = 0.017) and TSP2 High (HR 3.93, p = 0.009) as significant independent predictors of HCC occurrence after DAA therapy. The model had a high concordance index of 0.878. Additionally, combining TSP2 High and FIB-4 High (≥ 3.538) at SVR12 yielded high specificity and negative predictive value (0.941 and 0.917, respectively) for predicting HCC. Kaplan-Meier analysis showed a higher HCC incidence in the TSP2 High + FIB-4 High group (log-rank p < 0.0001). In conclusion, TSP2 may be a promising biomarker for personalised HCC surveillance in DAA-treated hepatitis C patients., (© 2024 The Author(s). Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Agents that target PD-1 and PD-L1 have been developed in the treatment of bladder cancer (BC). However, the diversity of immune cell infiltration in non-muscle-invasive BC (NMIBC) and the dynamics of the microenvironment as it progresses to muscle-invasive/metastatic disease remains unknown. To assess tumor immune activity, hierarchical clustering was applied to 159 BC samples based on cellular positivity for the defined immune cellular markers (CD3/CD4/CD8/FOXP3/CD20/PD-1/PD-L1/LAG3/TIGIT), divided into two clusters. There was a "hot cluster" (25%) consisting of patients with a high expression of these markers and a "cold cluster" (75%) comprising those without. The expression of CD39, CD44, CD68, CD163, IDO1, and Ki67 was significantly higher in tumors in the hot cluster. Immunologically, high-grade T1 tumors were significantly hotter, whereas tumors that had progressed to muscle invasion turned cold. However, a certain number of high-grade NMIBC patients were in the cold cluster, and these patients had a significantly higher risk of disease progression. Using an externally available TCGA dataset, RB1 and TP53 alterations were more frequently observed in TCGA hot cluster; rather FGFR3, KDM6A, and KMT2A alterations were common in TCGA cold/intermediate cluster. Analyses of recurrent tumors after BCG therapy revealed that tumor immune activity was widely maintained before and after treatment, and high FGFR3 expression was detected after recurrence in tumors initially classified into the cold cluster. Collectively, we revealed the dynamics of the tumor microenvironment in BC as a whole and identified candidate molecules as therapeutic targets for recurrent NMIBC, e.g., after BCG therapy., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

After half a century from their isolation in 1974, we report the first total syntheses of β- and γ-naphthocyclinones, two dimeric pyranonaphthoquinones featuring an unusual bicyclo[3.2.1]-octadienone core. The syntheses were achieved with full stereochemical control and functional group management, relying on 1) enantioselective construction of the bicyclic core by Rh-catalyzed enantioselective 1,4-addition followed by thiolate-mediated reductive cyclization, and 2) judicious design of a common chiral, non-racemic monomer unit that is capable of divergence into the donor and acceptor units, and reunion to construct the bicyclo[3.2.1]octadienone core., (© 2024 Wiley‐VCH GmbH.)

Abstract: α-Thalassemia (AT) is one of the most commonly occurring inherited hematological diseases. However, few treatments are available, and allogeneic bone marrow transplantation is the only available therapeutic option for patients with severe AT. Research into AT has remained limited because of a lack of adult mouse models, with severe AT typically resulting in in utero lethality. By using a lipid nanoparticle (LNP) targeting the receptor CD117 and delivering a Cre messenger RNA (mRNACreLNPCD117), we were able to delete floxed α-globin genes at high efficiency in hematopoietic stem cells (HSC) ex vivo. These cells were then engrafted in the absence or presence of a novel α-globin-expressing lentiviral vector (ALS20αI). Myeloablated mice infused with mRNACreLNPCD117-treated HSC showed a complete knock out (KO) of α-globin genes. They showed a phenotype characterized by the synthesis of hemoglobin H (HbH; also known as β-tetramers or β4), aberrant erythropoiesis, and abnormal organ morphology, culminating in lethality ∼8 weeks after engraftment. Mice infused with mRNACreLNPCD117-treated HSC with at least 1 copy of ALS20αI survived long term with normalization of erythropoiesis, decreased production of HbH, and amelioration of the abnormal organ morphology. Furthermore, we tested ALS20αI in erythroid progenitors derived from α-globin-KO CD34+ cells and cells isolated from patients with both deletional and nondeletional HbH disease, demonstrating improvement in α-globin/β-globin mRNA ratio and reduction in the formation of HbH by high-performance liquid chromatography. Our results demonstrate the broad applicability of LNP for disease modeling, characterization of a novel mouse model of severe AT, and the efficacy of ALS20αI for treating AT., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Elastin-like peptides (ELPs) exhibit lower critical solution temperature (LCST)-type behavior, being soluble at low temperatures and insoluble at high temperatures. While the properties of linear, long-chain ELPs are well-studied, short-chain ELPs, especially those with branched architectures, have been less explored. Herein, to obtain further insights into multimeric short ELPs, we investigated the temperature-responsive properties of branched molecules composed of a repeating pentapeptide unit of short ELPs, Phe-Pro-Gly-Val-Gly, as side components and oligo(Glu) as a backbone structure. In turbidimetry experiments, the branched ELPs showed LCST-like behavior similar to conventional ELPs and upper critical solution temperature (UCST)-like behavior, which are rarely observed in ELPs. In addition, the morphological aspects and mechanisms underlying the temperature-responsiveness were investigated. We observed that spherical aggregates formed, and the branched ELPs underwent structural changes through the self-assembly process. This study demonstrates the unique temperature-responsiveness of branched short ELPs, providing new insights into the future development and use of ELPs with tailored properties.

Sensory rhodopsin II (SRII) is a prototype photosensor that binds the retinal Schiff base chromophore. Upon photoabsorption, SRII is transformed into the signaling state, where two long-lived photointermediates are known to contribute. One is the M intermediate containing the deprotonated 13- cis chromophore, and the other is the O intermediate that is believed to have the protonated all- trans chromophore. The chromophore in the O intermediate is also thought to have the atypical 15- syn (C═N cis ) configuration about the Schiff base moiety. In this communication, we study SRII from Natronomonas pharaonis ( Np SRII) using Raman spectroscopy and find that the retinal chromophore configuration in the O intermediate is the 13- cis , 15- anti (C═N trans ), contrary to the conventional notion. This result points out the revision of the chromophore structural changes underlying the long-lived signaling state of SRII.

Objective: This study aimed to assess if prostate-specific antigen (PSA) threshold and PSA bounce are associated with oncological control after low-dose-rate brachytherapy (LDR-BT) alone or with external beam radiotherapy (EBRT), with or without androgen deprivation therapy (ADT), considering serum testosterone levels., Methods: This study enrolled 944 prostate cancer patients treated at a single institution with LDR-BT alone or LDR-BT combined with EBRT, with or without ADT. The Fine-Gray hazard model was used to evaluate factors related to clinical failure, including experience of PSA bounce between baseline and 2, 4, or 7 years after LDR-BT and PSA value (0.1, 0.2, or 0.5 ng/mL) with normal testosterone levels at 2, 4, and 7 years after LDR-BT, respectively., Results: Patients with normal testosterone levels and a PSA of 0.2 or 0.5 ng/mL at 2, 4, and 7 years after LDR-BT had a significantly better clinical failure free rate (CFFR) than those with PSA levels >0.2 or >0.5 ng/mL or low testosterone levels. Multivariate analysis revealed that PSA <0.1, 0.2, or 0.5 ng/mL with normal testosterone levels at 2, 4, and 7 years and experience of PSA bounce between baseline and 2 or 4 years after LDR-BT were significantly related to better CFFR., Conclusions: Patients with normal serum testosterone levels who reached PSA of <0.1, 0.2, or 0.5 ng/mL after LDR-BT, or those who experienced PSA bounce, showed better oncological control., (Copyright © 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Real-world data on health-related quality of life (HRQoL) in advanced urothelial carcinoma (aUC) receiving immune checkpoint inhibitors (ICIs) are limited. This study included 42 patients with aUC who received second-line or later pembrolizumab (n = 19), maintenance avelumab followed by first-line chemotherapy (n = 13), or adjuvant nivolumab after radical surgery (n = 10). Time-course changes in the domains and scales related to HRQoL were evaluated using the EORTC QLQ-C30, FACT-G, and SF-8 questionnaires during ICI therapy. Anchor-based approaches for minimally important differences were determined as 'improved', 'stable', and 'deteriorated'. We found significant improvements after the start of pembrolizumab treatment on many scales. Almost none of the scales changed significantly in the avelumab and nivolumab groups. Approximately 80% of the pembrolizumab group had deteriorated social/family well-being in FACT-G. Approximately 60% of the patients in the avelumab group had deteriorated general health and vitality in SF-8. In the nivolumab group, none of the scales deteriorated in > 50% of the patients. Deterioration of physical function in the SF-8 was associated with occurrence of treatment-related adverse events ≥ grade 2 during ICI therapy (P = 0.013). Our findings demonstrated that majority of patients with aUC who received ICI therapy had a stable HRQoL, which was consistent with evidence from clinical trials., (© 2024. The Author(s).)

Cerebrospinal fluid (CSF) circulation diseases, such as hydrocephalus and syringomyelia, are common in small-breed dogs. In human patients with CSF circulation diseases, time-spatial labeling inversion pulse (time-SLIP) sequence performed to evaluate CSF flow before and after treatment allows visualization of the restoration of CSF movement. However, studies evaluating CSF flow using the time-SLIP method in small-breed dogs are limited. Therefore, the present study aimed to evaluate intracranial CSF flow on time-SLIP images in small-breed dogs with idiopathic epilepsy, as an alternative model to healthy dogs. Time-SLIP images were obtained at two sites: 1) the mesencephalic aqueduct (MA) area (third ventricle, MA, and brain-base subarachnoid space [SAS]) and 2) the craniocervical junction area (fourth ventricle, brainstem, and cervical spinal cord SAS) to allow subsequent evaluation of the rostral and caudal CSF flow using subjective and objective methods. In total, six dogs were included. Caudal flow at the MA and brain-base SAS and rostral flow in the brainstem SAS were subjectively and objectively observed in all and 5/6 dogs, respectively. Objective evaluation revealed that a significantly smaller movement of the CSF, assessed as the absence of CSF flow by subjective evaluation, could be detected in some areas. In small-breed dogs, the MA, brain-base, and brainstem SAS would be appropriate areas for evaluating CSF movement, either in the rostral or caudal flows on time-SLIP images. In areas where CSF movement cannot detected by subjective methods, an objective evaluation should be conducted.

Background: Transcriptome-based prediction of complex phenotypes is a relatively new statistical method that links genetic variation to phenotypic variation. The selection of large-effect genes based on a priori biological knowledge is beneficial for predicting oligogenic traits; however, such a simple gene selection method is not applicable to polygenic traits because causal genes or large-effect loci are often unknown. Here, we used several gene-level features and tested whether it was possible to select a gene subset that resulted in better predictive ability than using all genes for predicting a polygenic trait., Results: Using the phenotypic values of shoot and root traits and transcript abundances in leaves and roots of 57 rice accessions, we evaluated the predictive abilities of the transcriptome-based prediction models. Leaf transcripts predicted shoot phenotypes, such as plant height, more accurately than root transcripts, whereas root transcripts predicted root phenotypes, such as crown root length, more accurately than leaf transcripts. Furthermore, we used the following three features to train the prediction model: (1) tissue specificity of the transcripts, (2) ontology annotations, and (3) co-expression modules for selecting gene subsets. Although models trained by a gene subset often resulted in lower predictive abilities than the model trained by all genes, some gene subsets showed improved predictive ability. For example, using genes expressed in roots but not in leaves, the predictive ability for crown root diameter was improved by more than 10% (R 2  = 0.59 when using all genes; R 2  = 0.66, using 1,554 root-specifically expressed genes). Similarly, genes annotated as "gibberellic acid sensitivity" showed higher predictive ability than using all genes for root dry weight., Conclusions: Our results highlight both the possibility and difficulty of selecting an appropriate gene subset to predict polygenic traits from transcript abundance, given the current biological knowledge and information. Further integration of multiple sources of information, as well as improvements in gene characterization, may enable the selection of an optimal gene set for the prediction of polygenic phenotypes., (© 2024. The Author(s).)

Targeting novel inhibitory ligands beyond anti-PD-1 and PD-L1 and CTLA-4 therapies is essential for the next decade of the immunotherapy era. Agents for the B7 family molecules B7-H3, B7-H4, and B7-H5 are emerging in clinical trial phases; therefore, further accumulation of evidence from both clinical and basic aspects is vital. Here, we applied a 7-color multiplexed imaging technique to analyze the profile of B7 family B7-H3/B7-H4/B7-H5 expression, in addition to PD-L1, and the spatial characteristics of immune cell infiltrates in urothelial carcinoma (UC). The results revealed that B7-H3 and B7-H4 were mainly expressed on tumor cells and B7-H5 on immune cells in UC, and most of the B7-H3/B7-H4/B7-H5-positive cells were mutually exclusive with PD-L1-positive cells. Also, the expression of B7-H4 was elevated in patients with advanced pathologic stages, and high B7-H4 expression was a significant factor affecting overall mortality following surgery in UC. Furthermore, spatial analysis revealed that the distance from the B7-H4 + cells to the nearest CD8 + cells was markedly far compared with other B7 family-positive tumor cells. Interestingly, the distance from B7-H4 + cells to the nearest CD8 + cells was significantly farther in patients dying from cancer after surgery or immune checkpoint inhibitors compared with cancer survivors; thus, high B7-H4 expression in tumor cells may inhibit CD8 infiltration into the tumor space and that B7-H4-positive cells form a specific spatial niche. In summary, we performed a comprehensive evaluation of B7 family member expression and found that the spatial distribution of B7-H4 suggests the potentially useful role of combination blockade with both B7-H4 and the current anti-PD-1/PD-L1 axis in the treatment of UC., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Controversial issues in registering candidates for deceased-donor kidney transplantation (DDKT) comprise various factors, including age, life expectancy, and dialysis duration. We investigated patient characteristics on the waiting list and discussed suitable criteria in Japan, which has a long waiting period., Methods: This study included 592 patients on the waiting list for DDKT at our institute between 1982 and 2023. We retrospectively reviewed patients' medical charts and obtained their clinical information. Patient characteristics according to outcomes and eligibility criteria for applying for or renewing registration were investigated. No prisoners were used in the study, and the participants were neither coerced nor paid., Results: Approximately 70%, 45%, and 14.5% of the registered patients were aged >60, >70, and 80 years, respectively. The number of patients aged ≥70 years gradually decreased over time. The median waiting periods of patients who underwent and interrupted DDKT were 13 and 7 years, respectively. Patients in their 70s with a >15-year dialysis period tended to have opportunities for DDKT. Living-donor kidney transplantation was performed in patients aged <60 years. Waiting patients were significantly younger and had a shorter dialysis duration. Advanced age at registration was associated with a significantly high risk of interruption., Conclusions: Advanced age and longer dialysis periods were considered at registration because patients with these factors tended to experience interruptions despite the long waiting period and high cost. Although older patients can undergo DDKT, factors including surgical cost and risks are considered. Eligibility/ineligibility criteria should be established for DDKT waiting lists in Japan., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background:  Treatment options for patients with differentiated thyroid cancer (DTC) who experience disease progression on lenvatinib treatment are limited. Although dose escalation of treatment with tyrosine kinase inhibitors at disease progression has been reported across cancer types, clinical significance in patients with DTC has not been investigated., Methods: We retrospectively reviewed patients with DTC who experienced disease progression on lenvatinib treatment from September 2011 to June 2022. We compared subjects who received dose-escalation treatment with standard treatment of termination at the time of initial disease progression. The escalated dose was decided by referencing to the previous effective and tolerated dose., Results: Thirty-three patients were identified, 15 with dose escalation and 18 with lenvatinib termination. In both groups, the starting dose of lenvatinib was 24 mg/day, and the median dose at initial disease progression was 10 mg/day. In the former, the median dose escalation was 6 mg/day (range: 4-12). Objective response rate, clinical benefit rate by escalation, and median treatment duration of the dose-escalation phase were 13.3%, 73.3%, and 9.9 months (95% confidence interval [CI] 5.71-27.6), respectively. Median overall survival from initial disease progression was significantly longer in the dose-escalation group (median OS: 20.4 months [95% CI 7.0-NA] vs. 3.9 months [95% CI 1.7-7.9], log-rank p-value; 0.0004, hazard ratio; 0.22 [95% CI 0.09-0.55]). There were no grade 5 adverse events, and one patient discontinued due to a grade 3 lung abscess., Conclusion: The dose-escalation strategy appears to be a safe and effective treatment option after disease progression in patients treated with lenvatinib for DTC., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: To assess the importance of appropriate opioid administration methods according to nociceptive monitoring., Methods: We conducted a randomized controlled trial involving 54 patients who underwent robot-assisted laparoscopic radical prostatectomy at our hospital. Patients were randomly allocated to either receive nociception level (NOL)-directed intraoperative opioid management with a minimum flow of remifentanil (NOL group) or conventional intraoperative analgesic management (control group). The primary outcome was the mean intraoperative remifentanil infusion flow rate (intraoperative remifentanil usage [μg]/ideal body weight [kg]/operation time [min]). The main secondary outcomes were plasma concentrations of three perioperative inflammatory biomarkers (interleukin-6, C-reactive protein [CRP], and cortisol levels) and postoperative pain (Numeric Rating Scale [NRS]) scores 2 h postoperatively and on postoperative days 1, 2, 3, and 7., Results: Compared with standard analgesia management, NOL-directed analgesic management reduced remifentanil consumption by 20% ( - 0.038; 95% confidence interval, - 0.059 to - 0.017; p = 0.0007). NOL-directed management did not lead to an increase in IL-6, CRP, or cortisol levels compared with conventional analgesic management. Furthermore, this protocol led to improvements in the NRS scores at rest 2 h postoperatively and upon movement up to postoperative day 3., Conclusion: NOL-directed analgesic management reduced remifentanil consumption by 20% and the NRS scores at rest 2 h postoperatively and upon movement up to postoperative day 3 without an increase in inflammatory marker levels., Registry Number: Japan Registry of Clinical Trials, JRCTs052220034., (© 2024. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Inhibition of the hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) represents a promising strategy for discovering next-generation treatments for renal anemia. We discovered DS44470011 in our previous study, which showed potent in vitro activity and in vivo efficacy based on HIF-PHD inhibition. However, DS44470011 was also found to exert genotoxic effects. By converting the biphenyl structure, which is suspected to be the cause of this genotoxicity, to a 1-phenylpiperidine structure, we were able to avoid genotoxicity and further improve the in vitro activity and in vivo efficacy. Furthermore, through the optimization of pyrimidine derivatives, we discovered DS-1093a, which has a wide safety margin with potent in vitro activity and an optimal pharmacokinetic profile. DS-1093a achieved an increase in hemoglobin levels in an adenine-induced rat model of chronic kidney disease after its continuous administration for 4 days., 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 Ltd. All rights reserved.)

Background: The number of patients with heart failure (HF) is rapidly increasing as palliative care is being integrated into HF management and the need for a nursing workforce to meet these demands grows. To address this, we have developed a Web-based educational program on primary palliative care for HF among general registered nurses caring for patients with HF in Japan., Objective: The aim of this study was to evaluate the program's effectiveness on nurse-reported palliative care practice, difficulty, and knowledge., Methods: In this open-label, individual-level, wait-listed randomized controlled trial, 150 Japanese general registered nurses, with experience in caring for patients with HF and clinical ladder level ≥ 2 in inpatient, outpatient, and home-visiting care settings, will be randomly divided (1:1 ratio) into a Web-based educational program group and a wait-list control group. The follow-up period is 6 months after the intervention. The primary outcome is the nurse-reported practice score in primary palliative care, and the secondary outcomes are the nurse-reported difficulties score and knowledge score., Conclusions and Clinical Implications: We herein describe the study protocol of a wait-listed randomized controlled trial regarding a Web-based educational program, which is a novel approach for these nurses. If the results of this study support our hypothesis, they could help expand primary palliative care, including daily nursing practices, such as symptom management and interdisciplinary collaboration, in the field of cardiovascular nursing., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A head-to-head comparison between enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) revealed similar survival benefits for castration-resistant prostate cancer (CRPC) in the ENABLE study for PCa. Considering that a dose reduction of ENZ and ABI has demonstrated sufficient inhibitory ability of androgen receptor (AR) signaling, we analyzed the efficacy of modified doses of these agents in the ENABLE study for PCa., Methods: This investigator-initiated, multicenter, randomized controlled trial that was conducted in Japan analyzed the prespecified survival endpoints, prostate-specific antigen (PSA) response rate ( ≥50% decline from baseline), and safety profile in patients treated with modified doses (ENZ ≤ 120 mg/day, ABI ≤ 750 mg/day) compared with those treated with a standard dose (ENZ 160 mg/day, ABI 1000 mg/day) as a starting dose., Results: In total, 92 patients in each arm were treated and analyzed; 16 patients were treated with a modified dose in both the ENZ and ABI arms, respectively. Moreover, 32 patients treated with modified doses showed a significantly better time to PSA progression (TTPP) and overall survival (OS) compared with the 152 patients treated with a standard dose (HR 0.47, 95%CI 0.27-0.83, p = 0.0379, and HR 0.35, 95%CI 0.19-0.63, p = 0.0162). Despite a significantly longer TTPP in the modified ABI group than in the standard ABI group (HR 0.29, 95%CI 0.14-0.62, p = 0.0248), no significant difference was observed in the TTPP between the modified and standard ENZ groups (p = 0.5366). Furthermore, similar adverse event rates and grades were observed in each treatment dose group., Conclusions: The modified doses of ABI showed better TTPP than the standard dose of ABI and may be a potential treatment option for CRPC patients; however, its mechanism is still unclear, although its ability to suppress AR signaling is equivalent to that of a standard dose., (© 2024 Wiley Periodicals LLC.)

Purpose: Bladder dysfunction associated with type 2 diabetes mellitus (T2DM) includes urine storage and voiding disorders. We examined pathological conditions of the bladder wall in a rat T2DM model and evaluated the effects of the phosphodiesterase-5 (PDE-5) inhibitor tadalafil., Materials and Methods: Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) rats were used as the T2DM and control groups, respectively. Tadalafil was orally administered for 12 weeks. Micturition behavior was monitored using metabolic cages, and bladder function was evaluated by cystometry. Bladder blood flow was evaluated by laser speckle imaging, and an organ bath bladder distention test was used to measure adenosine triphosphate (ATP) release from the bladder urothelium. The expression levels of vesicular nucleotide transporter (VNUT), hypoxia markers, pro-inflammatory cytokines and growth factors in the bladder wall were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Bladder wall contractions in response to KCl and carbachol were monitored using bladder-strip tests., Results: With aging, OLETF rats had higher micturition frequency and greater urine volume than LETO rats. Although bladder capacity was not significantly different, non-voiding bladder contraction occurred more frequently in OLETF rats than in LETO rats. Bladder blood flow was decreased and ATP release was increased with higher VNUT expression in OLETF rats than in LETO rats. These effects were suppressed by tadalafil administration, with accompanying decreased HIF-1α, 8-OHdG, IL-6, TNF-α, IGF-1, and bFGF expression. The impaired contractile responses of bladder strips to KCl and carbachol in OLETF rats with aging were restored by tadalafil administration., Conclusions: The T2DM rats had polyuria, increased ATP release induced by decreased bladder blood flow and impaired contractile function. PDE5 inhibition improved these changes and may prevent T2DM-associated urinary frequency and bladder storage and voiding dysfunctions., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Kabuto 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.)

Background: Undetectable circulating tumor DNA (ctDNA) is an obstacle to performing comprehensive genomic profiling in daily practice to identify genomic alterations. We investigated the associations between clinicopathological factors and undetectable ctDNA using a commercially available comprehensive genomic profiling assay in metastatic prostate cancer., Patients and Methods: Patients treated with systemic treatment for metastatic prostate cancer were included. ctDNA was analyzed by FoundationOne ® Liquid CDx at enrollment. The associations between clinicopathological characteristics and ctDNA detection were analyzed., Results: The number of bone metastasis was associated with ctDNA detection (odds ratio [95% confidence interval], 13.6 [1.71-108], P = 0.014). An algorithm predicting ctDNA detection using clinicopathological parameters was created. If ≥ 4 bone metastases were observed, ctDNA detection was estimated to be 98.9%. Among the patients with < 4 bone metastases, if two or three features among ISUP grade group 5, PSA level ≥ 10 ng/ml, and castration resistance were present, the ctDNA detection rate was 96.7% while the ctDNA detection rate was 86.3% if no or only one feature was present., Conclusions: An algorithm created in this study is helpful in determining when to undertake comprehensive genomic profiling assay using blood., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We report a case of dilated cardiomyopathy-like hypertensive cardiomyopathy (HTN-CM) with polycystic kidney disease without family history when a 3-month-old boy developed bacteraemia secondary to a urinary tract infection. He was later confirmed as having autosomal recessive inheritance due to the proven PKHD1 gene mutation. The treatment consisted mainly of antihypertensive and anti-heart failure therapies and he was discharged on the 131st day. To prevent the development of heart failure in patients with HTN-CM due to autosomal recessive polycystic kidney disease (ARPKD), it is important to improve the fetal diagnosis rate of ARPKD, detect hypertension early, and strictly control the blood pressure after birth.

Introduction: In this study, we aimed to identify biomarkers for predicting treatment outcomes and efficacy of chemotherapy plus nivolumab, as well as predict immune-related adverse events (irAEs) characteristics of immune checkpoint inhibitors., Methods: This multicenter study included 104 patients who received chemotherapy plus nivolumab as the primary treatment for unresectable advanced recurrent gastric cancer. Blood test results were collected before the start and after two courses of treatment. The neutrophil-lymphocyte ratio, prognostic nutritional index, and lactate dehydrogenase/albumin ratio (LAR) were examined after treatment in each case to determine changes compared to values before the start of treatment., Results: A total of 57 (54.8%) patients experienced a complete or partial response. The LAR of the stable disease/progressive disease group significantly increased (p = 0.018). An examination of the presence of grade ≥3 irAEs and changes in related factors showed that the LAR of all patients increased., Conclusion: The LAR was correlated with the best therapeutic response; therefore, it may be a potential biomarker of treatment outcomes and efficacy., (© 2024 S. Karger AG, Basel.)

Background: In patients with persistent atrial fibrillation (AF), extensive ablation for substrate modification, such as linear ablation or complex fractionated atrial electrogram ablation in addition to pulmonary vein isolation (PVI) remains controversial. Previous studies investigating extensive ablation have demonstrated its varying efficacy, suggesting the possible heterogeneity of its efficacy. Aging is a major risk factor for AF and is associated with atrial remodeling. We aimed to compare the efficacy and safety of the extensive ablation strategy compared with PVI alone strategy between young and elderly patients., Methods: This study is a post-hoc analysis of the multicenter, randomized controlled, noninferiority trial investigating the efficacy and safety of PVI-only (PVI-alone arm) compared with extensive ablation (PVI-plus arm) in patients with persistent AF (EARNEST-PVI trial). We divided the overall population into 2 groups based on age and assessed treatment effects., Results: In the young group (age <65 years, N = 206), there was no significant difference in the recurrence rate between the PVI-alone group and PVI-plus group [hazard ratio (HR): 1.00, 95 % CI: 0.57-1.73, p = 0.987], whereas the recurrence rate was significantly lower in the PVI-plus group compared to the PVI-alone group in the elderly group (age ≥65 years, N = 291) (HR: 0.47, 95 % CI: 0.29-0.76, p = 0.0021) (p for interaction = 0.0446). There were no fatal procedural complications., Conclusion: In patients with persistent AF, the extensive ablation strategy was more effective than the PVI-alone strategy in elderly patients, while the effectiveness of both approaches was comparable in young patients., Trial Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT03514693. URL: https://center6.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000022454 Unique ID issued by UMIN: UMIN000019449., Competing Interests: Declaration of competing interest Y. Sotomi has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical, TOA EIYO, Bristol-Myers Squibb, Biosense Webster, Abbott Medical Japan, and NIPRO, and personal fees from Abiomed, Abbott Medical Japan, AstraZeneca, Amgen Astellas BioPharma, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Boston Scientific Japan, Bayer, Daiichi Sankyo, Eli Lilly, Novartis, TERUMO, Medtronic, and Pfizer Pharmaceuticals. S. Hikoso has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical, Actelion Pharmaceuticals; and personal fees from AstraZeneca, Daiichi Sankyo, Astellas Pharma, Bayer, Pfizer Pharmaceuticals, Boehringer Ingelheim Japan, Kowa Company, and Ono Pharmaceutical. D. Nakatani has received personal fees from Roche Diagnostics. T. Dohi has received grants from Medtronic, Johnson & Johnson, and Abbott, during the conduct of the study. A. Sunaga has received grants from Medtronic, Johnson & Johnson, and Abbott, during the conduct of the study and personal fees from Bayer, Daiichi Sankyo, and Medtronic, outside the submitted work. M. Masuda has received personal fees from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson, Boston Scientific, Abbott, Nihon Kohden, Otsuka Pharmaceutical, AstraZeneca, and Medtronic, outside the submitted work. T. Watanabe has received personal fees from Biosense Webster, Abbott, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, Bayer, Daiichi Sankyo, Nihon Kohden, and Fukuda Denshi, outside the submitted work. H. Minamiguchi has received grants from Medtronic, Johnson & Johnson, and Abbott, during the conduct of the study, and personal fees from Medtronic, Abbott, Johnson & Johnson, Nihon Kohden, Biotronik, Japan Lifeline, Daiichi Sankyo, Bayer, Pfizer, Squibb, Boehringer Ingelheim, Kowa, Ono Pharmaceutical, and Otsuka Pharmaceutical, outside the submitted work. Y. Egami has received personal fees from Japan Lifeline and Medtronic, and non-financial support from Johnson & Johnson, Abbott, and Medtronic, outside the submitted work; T. Oka has received personal fees from Medtronic, Biotronik, Abbott, Daiichi Sankyo, Beyer, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, and AstraZeneca, outside the submitted work. Y. Matsuda has received personal fees from Daiichi Sankyo, Boehringer Ingelheim, Bayer, Medtronic, and Biotronik, outside the submitted work. M. Kawasaki has received personal fees from Medtronic, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Bristol-Myers Squibb, and Abbott, and grants from Osaka Heart Club, outside the submitted work. K. Inoue has received personal fees from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson, and Medtronic, outside the submitted work. Y. Sakata has received personal fees from Otsuka Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, AstraZeneca K.K. and Actelion Pharmaceuticals, and grants from Roche Diagnostic, FUJIFILM Toyama Chemical, Bristol-Myers Squibb, Co, Biosense Webster, Inc., Abbott Medical Japan, Otsuka Pharmaceutical, Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation, Astellas Pharma, Kowa Company, Boehringer Ingelheim Japan, and Biotronik. Other authors have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The number of older people in Japan is increasing more quickly than in other countries; with this aging of society, the number of elderly patients hospitalized for acute heart failure (HF) is also increasing. The treatment and prognosis of acute HF may be changing, but there are insufficient recent data, especially for octogenarian and older patients., Methods and Results: This study investigated the characteristics and treatment of acute HF patients in Japan. From 2018 to 2020, 1,146 patients from 7 Tokai area hospitals were followed for at least 1 year. The mean age was 78 years. Compared with patients aged <80 years, those aged ≥80 years were more likely to be female (57.4% vs. 34.2%), have a lower body mass index (22.2 vs. 24.9 kg/m 2 ), and have HF with preserved ejection fraction (43.1% vs. 21.4%), and less likely to have HF with reduced ejection fraction (38.9% vs. 61.7%). During hospitalization, 6.5% died. After discharge, patients faced high risks of rehospitalization for HF and death (27.6 and 14.2 per 100 patient-years, respectively). Notably, prescription rates of HF medications have declined over time for all patients, but especially for those aged ≥80 years., Conclusions: Guideline-directed medical therapy should be provided based on a thorough understanding of an individual's background rather than withheld simply because of clinical inertia due to a patient's advanced age.

An unguarded mitral valve orifice is a rare condition characterized by a thinned, hypocontractile left ventricle on fetal echocardiogram. This is the first report of an unguarded mitral valve orifice with a double-outlet right ventricle and intact ventricular septum diagnosed prenatally from these typical ultrasound features., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

The profunda artery perforator (PAP) flap, commonly used for small- to medium-sized breast reconstructions, offers easy harvest and inconspicuous donor-site scars. However, its shorter vascular pedicle compared with the deep inferior epigastric perforator flap limits its reach to lateral recipient vessels. This often requires strategic placement of perforators at the flap's edge to extend reach, potentially causing congestion in the distal part of the flap. To address these challenges, using the posterior accessory saphenous vein (pASV) has proven effective. Using the pASV as a vein graft significantly extends the pedicle length of the PAP flap, enhancing anastomosis success with recipient vessels. Additionally, in cases of flap congestion, the proximal segment of the pASV can be used as an additional venous outflow pathway, while grafting the distal segment further extends its length. This dual approach improves overall flap viability and reduces venous congestion risks. This discussion highlights two cases demonstrating the innovative use of the pASV within the PAP flap. In case 1, the pASV extended the pedicle length, enhancing the flap's placement flexibility and facilitating anastomosis with thoracodorsal vessels. In case 2, the pASV served as a secondary venous outflow pathway, with the distal segment grafted to extend the proximal portion. This adaptation provided additional venous drainage and effectively managed positioning constraints imposed by recipient vessel locations. These examples illustrate the significant benefits of utilizing the pASV in PAP flap breast reconstructions, offering a novel strategy to improve viability and expand its use in complex scenarios requiring extended vascular reach., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: There are few reports on conversion surgery (CS) after chemotherapy plus nivolumab as a first-line treatment in patients with unresectable advanced or recurrent gastric cancer (GC). This multicenter study was conducted to analyze real-world data on CS after chemotherapy plus nivolumab as a first-line treatment and to identify predictive biomarkers., Methods: This multicenter study included 104 patients who received chemotherapy plus nivolumab as primary treatment for unresectable advanced recurrent GC from 12 institutes. We investigated and analyzed patient characteristics and blood test data in the presence or absence of CS, the relationship between the Gustave Roussy Immune Score (GRIm-s) and CS, and the characteristics of CS cases., Results: CS was performed in 12 patients (11.5%). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was significantly better in patients who underwent CS (p < 0.0001). There were no CS cases with high-risk GRIm-s (0%), however there were 22 non-CS cases (23.9%). No high-risk GRIm-s cases were converted to CS. Minimally invasive surgery was performed in 50.0% of the cases, with R0 resection in all cases and only one case of urinary retention (Grade II) as a postoperative complication, indicating a good postoperative short-term outcome. There were two cases of postoperative recurrence (16.7%), both of which were grade 1b., Conclusions: The short-term postoperative results of CS after chemotherapy plus nivolumab as the first-line treatment for GC were acceptable in this study. There were no high-risk GRIm-s cases among those who underwent CS, suggesting that the GRIm-s may be a predictor of CS., (© 2024. Society of Surgical Oncology.)

Phytochemical study on the flowers of Hypericum formosanum Maxim. (Hypericaceae) led to the isolation of formohyperins G-L (1-6), whose structures were assigned by detailed spectroscopic analysis. Formohyperins G-L (1-6) are new benzoylphloroglucinols substituted by a C 10 unit, a prenyl group, and a methyl group. Formohyperins G-J (1-4) possess a 6/6/6-tricyclic structure, while formohyperins K (5) and L (6) have a unique 6/6/5/4-tetracyclic structure consisting of cyclohexadienone, dihydropyrane, cyclopentane, and cyclobutane rings. The absolute configurations of 1-6 were deduced by analysis of the ECD spectra. Formohyperins G-J (1-4) and L (6) were found to show potent inhibitory activities against IL-1β release from LPS-treated murine microglial cells with EC 50 values of 5.0, 10.9, 6.3, 10.8, and 13.7 µM, respectively, without cytotoxicity. 6-O-Methylformohyperins G (1a) and I (3a) also exhibited the inhibitory activities with EC 50 values of 4.7 and 2.7 µM, respectively, although they were cytotoxic against microglial cells., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)