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We have reported that a combination of delipation (removal of cytoplasmic lipid droplets from blastomeres) and vitrification by means of the minimum-volume cooling (MVC) method successfully cryopreserves porcine in vitro-matured/fertilized (IVM/IVF) embryos, and that normal piglets are produced from these embryos (Hiruma et al. 2006 Reprod. Fertil. Dev. 18, 157). We have also reported that IVM-derived embryos that undergo noninvasive delipation (i.e. micromanipulation is not required) and vitrification develop into blastocysts at a high rate (Esaki et al. 2004 Biol. Reprod. 71, 432–437). In this study, we examined whether fetuses can be produced from the IVM-derived embryos that have been delipated noninvasively and vitrified. Cumulus–oocyte complexes that had been collected from slaughterhouse ovaries were in vitro-matured in NCSU23 medium. The IVM oocytes were activated to produce parthenogenetic embryos. We used the embryos at the 4- to 8-cell (67 h after activation) and morula (98 h) stages in the following experiments. Embryos were treated with 4% trypsin (in PBS) at 38C for 1 to 4 min to expand the zona pellucida. Next, the embryos were centrifuged (12 000g, 38C, 23 min) in TL-HEPES-PVP containing 7.5 g mL-1 cytochalasin B to polarize cytoplasmic lipid droplets within the perivitelline space. These embryos were cultured for 1 to 3 h and then vitrified. The post-thaw viability of the embryos was assessed based on their ability to develop into blastocysts and fetuses (21 to 23 days old). The embryos were vitrified using the MVC method with 15% ethylene glycol, 15% DMSO, and 0.5 M sucrose as cryoprotective agents. PZM-5 was used for culturing the embryos. In embryo transfer experiments, after thawing, the embryos were cultured for 36 or 72 h until they developed into morulae or 4- to 8-cell blastocysts, respectively; they were then treated with 0.5% pronase to remove the zona pellucida, and transferred to the uterine horns of estrus-synchronized recipients 6 days after onset of estrus. The proportion of vitrified embryos that developed into blastocysts and the mean cell number of the blastocysts were similar to those of non-vitrified control embryos, irrespective of the embryonic stage (4- to 8-cell stage: 42.1%, 22/51, 63.0 7.8 vs. 64.7%, 22/34, 74.2 7.1, respectively; morula stage: 77.6%, 38/49, 69.6 7.2 vs. 83.3%, 45/54, 66.2 5.9, respectively). Seventeen embryos that had been vitrified at the 4- to 8-cell stage gave rise to 3 fetuses after transfer into one recipient (17.6%). Fifty-three embryos that had been vitrified at the morula stage were transferred into 3 recipients. All recipients became pregnant and produced a total of 17 fetuses (32.1%). These results suggest that porcine IVM-derived embryos that have been cryopreserved by the combination of noninvasive delipation and vitrification by the MVC method are highly viable. [ABSTRACT FROM AUTHOR]

Cryopreservation of mammalian metaphase-II (M-II) oocytes is still impractical compared to that of early stage embryos. In this study we examined the effects of delipation and mitotic spindle stabilization in order to improve the post-vitrification survival rate of in vitro-matured (IVM) porcine oocytes at the M-II stage. Cumulus–oocyte complexes that had been collected from slaughterhouse ovaries were matured in vitro in NCSU23 supplemented with 0.6 mm cysteine, 10 ng mL–1 epidermal growth factor (EGF), 10% porcine follcular fluid (PFF), and 10 IU mL–1 eCG and hCG. The denuded M-II oocytes were vitrified in the presence of 30% ethylene glycol and 0.5 m sucrose using the minimum volume cooling (MVC) method with a MVC plate (Cryotop; Kitazato Supply, Tokyo, Japan). Vitrified embryos were rewarmed by immersing the MVC plate directly into rewarming solution containing 1 m sucrose and 20% calf serum at 39C for 1 min, followed by stepwise dilution of the cryoprotectants. We compared the effects of previtrification treatments, namely, (1) delipation, (2) mitotic spindle stabilization, (3) delipation + mitotic spindle stabilization, and (4) no treatment. For delipation, we used a noninvasive method (Esaki et al. 2004 Biol. Reprod. 71, 432–437) that we had published previously with slight modification. The embryos were treated with 4% trypsin at 38C for approximately two min to expand the zona pellucida, and then centrifuged (12 000g, 38C 23 min) with 7.5 µg mL–1 cytochalasin B to polarize cytoplasmic lipid droplets within the perivitelline space. For mitotic spindle stabilization, M-II oocytes were vitrified in the presence of 1 µm paclitaxel. After the oocytes were rewarmed, electrical activation of the oocytes (150 V mm–1, 100 µs, one time) was carried out to induce parthenogenesis. These parthenogenetic embryos were cultured in PZM-5 for 7 days, and the number of vitrified embryos that developed into blastocysts with respect to each treatment was determined. The blastcyst formation rate and mean cell numbers of the blastcysts were compared among the treatment groups (chi-square test, Tukey''s test). Of the 50 M-II oocytes that had been vitrified without pretreatment, only one oocyte (2.0%) developed into a blastocyst with 20 cells. By contrast, the number of vitrified embryos that developed into blastocysts was significantly high when they were delipated prior to vitrification (37.8%, 14/37, 64.0 9.6; P < 0.01). Mitotic spindle stabilization also improved the survival rate of vitrified oocytes (18.6%, 21/113, 56.7 9.6; P < 0.01). The combination of delipation and mitotic spindle stabilization produced the highest number of vitrified oocytes that developed into blastocysts (43.8%, 35/80, 69.4 6.4), although the difference between the combination group and the delipation group was not significant. These results indicate that blastocysts can be produced very efficiently from IVM porcine oocytes that have been vitrified at the M-II stage using both noninvasive delipation and mitotic spindle stabilization procedures. [ABSTRACT FROM AUTHOR]

Cloned pigs that express cell markers such as fluorescent proteins (Vintersten et al. 2004 Genesis 40, 241–246) are useful in biomedical research in areas such as cell/tissue transplantation and regenerative medicine. In this study, we attempted to produce transgenic cloned pigs from porcine fetal fibroblasts which carry the gene of red fluorescent protein, humanized Kusabira-Orange (huKO). We examined whether huKO-transfected cells are suitable as nuclear donors for somatic cell cloning, and whether red fluorescence can be detected in the cloned embryos. We used porcine fetal fibroblasts transfected with the huKO gene and a retroviral vector as the nuclear donor cells. Non-transfected cells were used as the control. Cumulus–oocyte complexes collected from slaughterhouse ovaries were in vitro-matured in NCSU23 medium to produce recipient oocytes. Nuclear transfer was conducted using a previously reported method (Kurome et al. 2003 Cloning Stem Cells 5, 367–377); the following parameters which determine the overall efficiency of nuclear transfer were investigated: (1) fusion rate between the donor cells and recipient oocytes, (2) rates of normal cleavage and blastocyst formation of the NT embryos, and (3) cell numbers in each blastocyst. A DC pulse (190 V mm-1) was used for electric fusion, and NCSU23 or PZM-5 medium was used for culturing the cloned embryos. The NT embryos on Day 7 were examined under a fluorescence microscope (G excitation) in order to evaluate the expression of red fluorescence. Some cloned embryos at the 1- to 8-cell stage (Day 1 or 2) were transferred into oviducts of estrus-synchronized recipient gilts. There was no significant difference (chi-square test) between the huKO and the control groups in the rate of fusion (132/151, 87.4% vs. 134/147, 91.2%, respectively) and cleavage rate (78/132, 59.1% vs. 86/134, 64.2%, respectively). A significantly greater percentage of huKO cell-derived embryos developed into blastocysts than did control cell-derived embryos (37/132, 28.0% vs. 20/134, 14.9%, respectively; P < 0.05). However, there was no significant difference in the blastocyst cell numbers (Student''s t-test: 48.6 ± 4.8 vs. 42.3 ± 4.9, respectively). Of the 132 NT embryos, 116 (87.9%) expressed red fluorescence. The percentage of blastocysts expressing red fluorescence was 94.6% (35/37). These results demonstrate that it is possible to obtain cloned blastocysts at a high rate by nuclear transfer of cells that have been transfected with huKO using a retroviral vector, and that it is possible to observe the expression of red fluorescence in cloned embryos. With respect to the cloned embryos that did not show expression of red fluorescence, we hypothesize that this was the result of a small proportion (<1%) of donor cells which also lacked red fluorescence expression. An ultrasonic echo examination has confirmed that all 3 of the recipients which had received 93 to 119 embryos became pregnant.This study was supported by PROBRAIN. [ABSTRACT FROM AUTHOR]

Transgenic (Tg)-cloned pigs expressing fluorescent proteins are very useful in research such as cell or tissue transplantation studies. In this study, we produced Tg-cloned pigs with an orange fluorescent protein, humanized Kusabira-Orange (huKO), and analyzed the characteristics of these pigs. Fetal fibroblast cells transduced with huKO gene by a gene silencing-resistant retroviral vector, pDΔNhuKO (Suzuki et al. 2002 J. Neurochem. 82, 953–960) were used as nuclear donors. Recipient cytoplasts were prepared using oocytes matured in vitro in NCSU23. The nuclear transfer (NT) embryos were transferred into oviducts of estrus-synchronized recipient gilts after culture in PZM-5 for 1 or 2 days. Cloned pigs obtained were analyzed by Southern blotting for the transgene integration. A total of 23 organs and tissues, including brain, eye, internal and reproductive organs, skin, skeletal muscle, and cartilage were examined by fluorescence stereomicroscopy. Cryo- and paraffin-embedded tissue sections were also prepared to examine fluorescence expression. Immunofluorescent staining of brain cryosection and flow cytometry analysis of peripheral blood cells were performed to identify huKO-expressing cells. Transfer of 429 NT embryos into 4 recipients resulted in 18 (4.2%) cloned offspring. Southern blotting analysis of the cloned pigs confirmed transduction of 2 to 17 copies of the huKO gene in each pig. Autopsy was performed in 6 pigs, and orange fluorescence was confirmed in all the tissues and organs examined in each pig. In addition, prominent orange fluorescence was detected in pancreatic islets and renal glomeruli, indicating that these transgenic pigs are ideal for islet cell transplantation studies. Expression of huKO was also detected in neurons, microglia, and astrocytes in the brain, and granulocytes, monocytes, macrophages, lymphocytes, and platelets in the peripheral blood cells, whereas the expression level in red blood cells was lower. Re-cloning was performed using primary culture fibroblast cells established from 2 Tg-cloned pigs. Transfer of 300 re-cloned embryos into 4 recipients resulted in 3 pregnancies. A re-cloned fetus at Day 44 of gestation showed systemic fluorescence. These results demonstrate that the retroviral vector pD?NhuKO is resistant to gene silencing in pigs, that transduction and expression of the huKO gene had no lethal effects on fetal development, and that a Tg-cloned pig expressing orange fluorescence can be produced by NT of fetal fibroblast cells transduced with the huKO gene.This study was supported by PROBRAIN. [ABSTRACT FROM AUTHOR]

We previously reported that transgenic (TG) pigs can be produced from in vitro-matured oocytes using intracytoplasmic sperm injection-mediated gene transfer (ICSI-mediated method) (Kurome et al. 2006 Transgenic Res. 15, 229–240). We subsequently studied the expression of a foreign gene which had been introduced by the ICSI-mediated method. We found that the ICSI-mediated method is considerably less likely than the pronuclear microinjection method to produce embryos in which transgene-positive and transgene-negative cells co-exist, that is, mosaic embryos (Saito et al. 2006 Reprod. Fertil. Dev. 18, 297 abst). Therefore, in order to further investigate the ICSI-mediated method, the present study was conducted to address the integration patterns of foreign genes introduced by this method. In particular, we wished to determine the number of transgene copies and number of chromosomal integration sites. TG pig fetuses, obtained by the ICSI-mediated method in a separate cardiac disease model study, were used in the present study. Porcine cumulus-oocyte complexes that had been collected from slaughterhouse ovaries were subjected to in vitro maturation in NCSU23 medium to produce MII oocytes to be used in this study. Porcine spermatozoa frozen in Beltsville Thawing Solution (BTS) were thawed rapidly in a 37C water bath, and each spermatozoon was decapitated using ultrasound (28 kHz, 100 W; W-113; Honda Electronics Co., Ltd, Aichi, Japan). The heads (2 to 5 105/10 L) were co-incubated with 2.5 ng L-1 of rabbit calreticulin cDNA (MHC-CRT-HA: 7.5 kb) for five min at room temperature, and then microinjected into MII oocytes using a piezo-micromanipulator. An electric stimulus (DC 150 V mm-1, 100 s) was applied 10 to 40 min after microinjection in order to activate the oocytes. The embryos were cultured in PZM-5 medium for one to two days, and then transferred into the oviducts of recipient gilts, whose estrous cycle had been synchronized using 1000 IU eCG and 1500 IU hCG. Fetuses were collected 33 or 50 days later, and a primary cell line (fibroblast) was established. For each fetus, the number of transgene copies was determined by Southern blot. In addition, the chromosomal sites, where the foreign gene had integrated, were identified, and the number of integration sites was determined by fluoresent in situ hybridization (FISH). A total of 454 ICSI embryos were transferred to 4 recipients (92 to 135 embryos/recipient). All recipients became pregnant and 23 fetuses (5.1%, 23/454), including 7 TG fetuses (30.4%, 7/23), were obtained. Southern blot analysis showed that the number of transgene copies varied between 1 and 300 (1 copy: 1 fetus; 10 copies: 2 fetuses; 30 copies: 3 fetuses; 300 copies: 1 fetus). FISH analysis showed that in TG fetuses, the foreign gene had integrated at only a single chromosomal site, and this site varied from TG fetus to TG fetus. These results demonstrate that, in the case of ICSI-mediated gene transfer, as is the case for gene transfer by pronuclear microinjection, the integration patterns are: multiple copy, random site, and single site integration.This study was supported by PROBRAIN. [ABSTRACT FROM AUTHOR]

A 75-year-old Japanese woman experienced persistent fatigue and progressive jaundice for 6 weeks, and was subsequently diagnosed with acute liver failure. She had not received any immunosuppressive therapies and/or antineoplastic chemotherapy. Blood tests revealed elevated levels of HBsAg, HBV-DNA, and anti-HBc IgG, while anti-HBc IgM was negative. She had undergone hepatitis virus testing 48 weeks earlier, during which HBsAg was negative, indicating that HBV reactivation occurred in a patient with a previously resolved infection, without any drug therapies as triggers, ultimately leading to acute liver failure. Despite receiving multidisciplinary intensive treatment, her condition worsened, resulting in death. Full-length genomic analysis of the HBV strain, performed using nanopore sequencing technology, identified an I126S substitution in HBsAg, known as a vaccine escape mutation, along with a quasispecies consisting primarily of two HBV clone variants: one full-length and the other with a deletion in the nt2,448-nt488 region (sp1 spliced variant). These genetic factors may have contributed to the spontaneous HBV reactivation., Competing Interests: Declarations. Conflict of interest: Satoshi MOCHIDA has received speaking fees or honoraria from Abbvie GK, Gilead Sciences Inc., Ohtsuka Pharmaceutical Co. Ltd., Torey Medical Co. Ltd, Eisai Co., Ltd. Asuka Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co., Ltd., has received research grants from Abbvie GK, Eisai Co., Ltd. Sumitomo Pharma Co., Ltd. intellim Corporation. Human rights: All the procedures were performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. Informed consent: Informed consent was obtained from the patient to publish the clinical and virological findings., (© 2024. Japanese Society of Gastroenterology.)

The frozen domain (FD) approximation with the fragment molecular orbital (FMO) method is efficient for partial geometry optimization of large systems. We implemented the FD formulation (FD and frozen domain dimer [FDD] methods) already proposed by Fedorov, D. G. et al. ( J. Phys. Chem. Lett. 2011 , 2, 282-288); proposed a variation of it, namely frozen domain and partial dimer (FDPD) method; and applied it to several protein-ligand complexes. The computational time for geometry optimization at the FDPD/HF/6-31G* level for the active site (six fragments) of the largest β 2 -adrenergic G-protein-coupled receptor (440 residues) was almost half that of the conventional partial geometry optimization method. In the human estrogen receptor, the crystal structure was refined by FDPD geometry optimization of estradiol, surrounding hydrogen-bonded residues and a water molecule. The rather polarized ligand binding site of influenza virus neuraminidase was also optimized by FDPD optimization, which relaxed steric repulsion around the ligand in the crystal structure and optimized hydrogen bonding. For Serine-Threonine Kinase Pim1 and six inhibitors, the structures of the ligand binding site, Lys67, Glu121, Arg122, and benzofuranone ring and indole/azaindole ring of the ligand, were optimized at FDPD/HF/6-31G* and the ligand binding energy was estimated at the FMO-MP2/6-31G* level. As a result of examining three different optimization regions, the correlation coefficient between pIC 50 and ligand binding energy was considerably improved by expanding the optimized region; in other words, better structure-activity relationships was obtained. Thus, this approach is promising as a high-precision structure refinement method for structure-based drug discovery.

A seventh blind test of crystal structure prediction has been organized by the Cambridge Crystallographic Data Centre. The results are presented in two parts, with this second part focusing on methods for ranking crystal structures in order of stability. The exercise involved standardized sets of structures seeded from a range of structure generation methods. Participants from 22 groups applied several periodic DFT-D methods, machine learned potentials, force fields derived from empirical data or quantum chemical calculations, and various combinations of the above. In addition, one non-energy-based scoring function was used. Results showed that periodic DFT-D methods overall agreed with experimental data within expected error margins, while one machine learned model, applying system-specific AIMnet potentials, agreed with experiment in many cases demonstrating promise as an efficient alternative to DFT-based methods. For target XXXII, a consensus was reached across periodic DFT methods, with consistently high predicted energies of experimental forms relative to the global minimum (above 4 kJ mol -1 at both low and ambient temperatures) suggesting a more stable polymorph is likely not yet observed. The calculation of free energies at ambient temperatures offered improvement of predictions only in some cases (for targets XXVII and XXXI). Several avenues for future research have been suggested, highlighting the need for greater efficiency considering the vast amounts of resources utilized in many cases., (open access.)

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern. The use of CSP in the prediction of likely cocrystal stoichiometry was also explored, demonstrating multiple possible approaches. Crystallographic disorder emerged as an important theme throughout the test as both a challenge for analysis and a major achievement where two groups blindly predicted the existence of disorder for the first time. Additionally, large-scale comparisons of the sets of predicted crystal structures also showed that some methods yield sets that largely contain the same crystal structures., (open access.)

Background: The EF-14 clinical trial demonstrated the safety and efficacy of tumor-treating fields (TTFields) for newly diagnosed glioblastoma. This study aimed to clarify the current status, safety, and efficacy of TTFields in Japanese patients who meet the EF-14 inclusion criteria., Methods: This was a multicenter retrospective cohort study. Background, treatment, and outcome data of patients who satisfied the inclusion criteria of the EF-14 trial were collected from 45 institutions across Japan. The rate, determinants, and current status of TTField use, including its safety and efficacy in terms of progression and survival, were retrospectively investigated. This study was conducted in accordance with the STROBE checklist., Results: Among the 607 patients enrolled, 70 were excluded due to progressive disease during radiation and temozolomide therapy, age > 80 years old, and Karnofsky Performance Status score of <70. Among the remaining 537 patients, 210 (39%) underwent TTField treatment. Multivariate analysis revealed younger age and spouse as a caregiver as significant factors for TTField use. The compliance rate of TTField use exceeded 75% in 60% of patients, with a median TTField usage duration of 11 months. Skin disorders requiring medical treatment occurred in 56% of patients. Multivariate Cox proportional hazards analysis in the whole series and propensity score-matched analysis revealed that TTField use was not a prognostic factor for progression-free survival (PFS) or overall survival (OS)., Conclusions: TTField use did not have a substantial effect on either PFS or OS in Japanese patients with glioblastoma, despite compliance rates comparable to those observed in the EF-14., Competing Interests: M.Ka. received honoraria from Novocure and Eisai and research funding from Eisai. K.S. received honoraria from Novocure and Eisai and research funding from Eisai and Nippon Kayaku. S.Y. received honoraria from Novocure. M.N. received honoraria from Novocure and Eisai. T.M. received honoraria from Novocure and Eisai. M.N. received honoraria from Novocure, Eisai, and Nippon Kayaku and research funding from Eisai and MSD. K.Y. received honoraria from Novocure. H.Y. received honoraria from Novocure and Eisai. Y.Nakahara received honoraria from Novocure and Eisai. Y.H. received honoraria from Novocure and Eisai and research funding from Eisai. M.Ki. received honoraria from Novocure and Eisai. A.Y. received research funding from Eisai. Y.K. received honoraria from Novocure and Eisai. M.T. received research funding for clinical trial from Eisai. Y.A. received honoraria from Novocure, Eisai, and Nippon Kayaku. Y.Narita received honoraria from Novocure and Eisai and research funding from Eisai. All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Increased use of electronic devices such as smartphones has led to an increase in neck and shoulder stiffness to the forefront of the public people. It is said that prolonged posture with the head tilted forward causes excessive muscle activity in the head and neck region, resulting in muscle fatigue symptoms such as stiff shoulders. Various bathing methods have been proposed as a means of recovering from muscle stiffness, and in particular, contrast water therapy (CWT) is said to be highly effective in recovering from muscle fatigue. In the present study, we examined the effect of CWT with hot and cold stimulation of the neck and shoulders (CWTNS) on muscle fatigue recovery. As the result, in the CWTNS condition, the effects of vasodilation and vasoconstriction were observed, and muscle hardness was significantly lower than that in the Control condition in 20 subjects (2 males, 18 females). Stress hormones were also decreased during and after bathing compared to those before bathing. These results motivate further exploration of the possibility that the effects of CWTNS could be muscle-recovery without high stress load., Competing Interests: Declarations. Informed consent: Informed consent was obtained from all individual participants included in the study. Institutional review board statement: This study was approved by the Regional Board of Aichi Medical University. Conflict of interest: Ryoko Nomura, Kei Watanabe, and Tomohisa Kato are employees of TOTO Ltd. Satoshi Iwase received a research grant from TOTO Ltd., (© 2024. The Author(s) under exclusive licence to International Society of Biometeorology.)

Purpose: The laparoscopic approach (LA) for repairing inguinal hernias (IH), especially laparoscopic extraperitoneal percutaneous closure (LPEC) has become popular minimally invasive surgical technique. However, invasiveness is difficult to evaluate in children of < 5 years of age, as they cannot adequately express their pain. The current study utilized a pain scoring system compare pain in patients of < 5 years of age who were treated by LA or traditional open approach (OA)., Methods: The records of 74 IH patients of < 5 years of age who underwent surgery in our hospital between January 2022 and July 2023 were reviewed. Revised Face, Legs, Activity, Cry, and Consolability (FLACC) scores were used to quantitatively evaluate the degree of pain., Results: Forty-seven patients (mean age, 2.85 years) underwent treatment with an OA, and 27 patients (mean age, 2.37 years) underwent treatment with an LA. The FLACC scores in the OA and LA groups were 0.21 and 0.44, respectively. In a subanalysis by age groups, The FLACC scores in the OA and LA groups were 0.09 and 0.5 in patients of < 2 years of age, respectively, CONCLUSION: The reduced invasiveness of LA relative to OA did not minimize postoperative pain, especially in patients < 2 years of age., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: An increasing number of drug-resistant bacteria have been identified recently. In particular, drug-resistant bacteria have been linked to unfavorable prognoses in patients with bacteremia, highlighting the need for rapid testing. Our previous studies have focused on the utility of a drug susceptibility testing microfluidic (DSTM) method using microfluidic channels. A system with this DSTM method for screening for β-lactamases can rapidly detect extended-spectrum β-lactamases (ESBLs) and metallo-β-lactamases (MBLs). In this study, we have evaluated the clinical utility of pre-treatment for screening positive blood cultures using the DSTM method., Methods: A total of 178 positive blood cultures and five simulated samples of MBL-producing bacteria were prepared at Kochi University Hospital, Japan. The pretreatment consisted of a two-step centrifugation. The obtained sediments were screened with the DSTM method for the production of β-lactamase based on morphological changes in the bacteria after 3 h of incubation., Results: The pretreatment functioned properly for all samples. Of the 25 ESBL samples, 21 were positive for ESBLs. Four false-negative samples, all obtained from the same patient, contained CTX-M-2 enzyme-producing Proteus mirabilis and showed insusceptibility to an ESBL inhibitor. The simulated samples prepared for MBL screening were positive for MBLs., Conclusions: When combined with a method for rapidly identifying bacterial species, DSTM may enable patients with bloodstream infections to start receiving appropriate treatment within 4 h after positive blood cultures are screened., Competing Interests: Declaration of competing interest This study was conducted in collaboration with Fukoku., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Covert hepatic encephalopathy (CHE) significantly impacts the quality of life and prognosis in patients with liver cirrhosis. This study aims to analyze the prevalence and risk factors of CHE to identify high-risk patients who would benefit from therapeutic interventions., Methods: This single-center, retrospective observational study included 126 patients without a history of overt hepatic encephalopathy (OHE). CHE was defined as a score above the age-based cutoff value in the Stroop test. Factors associated with the occurrence of CHE and the subsequent development of OHE were evaluated., Results: CHE was detected in 47 patients (37.3%). A multiple logistic regression analysis identified serum zinc levels (per + 1 µg/dL, odds ratio 0.95, P = 0.0007) as the only risk factor associated with CHE, with a cutoff value of 60 µg/dL (AUC 0.71, P = 0.0001). Neither blood ammonia levels nor liver function were predictive of CHE. During a median observation period of 211 days, OHE developed in 18 patients (14.3%). The administration of more than 20 mg of furosemide was identified as a risk factor for developing OHE (hazard ratio 23.52, P = 0.0207)., Conclusion: Cirrhotic patients with serum zinc levels below 60 µg/dL exhibit a high risk of developing CHE, regardless of blood ammonia levels. These patients face a significant risk of developing OHE. Therefore, early zinc supplementation is recommended for the prevention of OHE, particularly for those prescribed 20 mg or more of furosemide., (© 2024. Japanese Society of Gastroenterology.)

Background: Cystic formation due to radiation necrosis in metastatic brain tumors is a rare condition. Surgical intervention is necessary if symptoms develop. Additionally, excising radiation necrosis lesions within the cyst is essential to prevent recurrence. Neuroendoscopic surgery is a minimally invasive method suitable for treating cystic diseases and accessing deep lesions in the brain. The authors herein present a method for removing radiation necrotic tissue from deep lesions of cystic radiation necrosis using neuroendoscopy., Observations: Endoscopic surgery was performed in two patients with symptomatic cystic radiation necrosis. Both cases involved multilocular cysts, with radiation necrosis located deep within the cyst. The authors performed a small craniotomy of approximately 3 cm and opened the cyst. After removing its contents, an endoscope was used to closely observe the interior of the cyst. Removal of the septum within the cyst allowed the endoscope to be inserted deeply. The authors identified and excised the nodular lesion diagnosed as radiation necrosis in the deep tissue. Following the surgery, the cyst shrank rapidly, and symptoms disappeared. Both patients showed no recurrence of the lesions., Lessons: The authors performed minimally invasive surgery and achieved good outcomes. Endoscopic surgery was considered beneficial for treating cystic radiation necrosis. https://thejns.org/doi/10.3171/CASE24250.

Liver transplantation is often the only lifesaving option for acute liver failure (ALF); however, the predictors of short-term mortality (death within one year) after living donor liver transplantation (LDLT) for ALF have yet to be defined. We retrospectively collected patients ≥18 years old who underwent LDLT for ALF between 2010 and 2020 at 35 centers in Asia. Univariate and multivariate logistic regression analyses were conducted to identify the clinical variables related to short-term mortality and establish a novel scoring system. The Kaplan-Meier method was performed to explore the association between the score and overall survival. Of the 339 recipients, 46 (13.6%) died within 1 year after LDLT. Multivariate analyses revealed 4 independent risk factors for death: use of vasopressors or mechanical ventilation, the higher model for end-stage liver disease score, and a lower graft-to-recipient weight ratio. The internally validated c-statistic of the short-term mortality after transplant (SMT) score derived from these 4 variables was 0.80 (95% confidence interval: 0.74-0.87). The SMT score successfully stratified recipients into low-, intermediate-, and high-risk groups with 1-year overall survival rates of 96%, 80%, and 50%, respectively. In conclusion, our novel SMT score based on 4 predictors will guide ALF recipient and living donor selection., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: Patients with chronic hepatitis B virus (HBV) infection experiencing viral breakthrough (BTH) or partial response (PR) during lamivudine (LAM) or entecavir hydrate (ETV) administration often took ETV plus tenofovir alafenamide fumarate (TAF) due to the emergence of a drug-resistance mutation. However, in patients lacking drug-resistance mutation against TAF, sufficient antiviral effects may be achievable with TAF monotherapy. We assessed the drug-resistance profile through nucleotide sequences of HBV pregenome RNA, and subsequently changed to TAF monotherapy from ETV plus TAF., Methods: This prospective study included 25 patients with serum HBV-DNA below 20 IU/mL under ETV plus TAF administration. Pregenome RNA nucleotide sequences of HBV in the sera were analyzed using direct sequencing and deep sequencing. ETV was discontinued in patients without rtA194T and rtS106C + rtH126Y + rtD134E + rtL269I quadruple mutations in direct sequencing., Results: LAM-PR, LAM-BTH, ETV-PR, and ETV-BTH were observed in 1, 16, 7, and 1 patient(s), respectively. Pregenome RNA nucleotide sequences were analyzable in 20 patients. Among the 12 patients classified as LAM-BTH, six patients showed rtL180M + rtM204V/I in direct sequencing, and one patient showed minor clones containing rtL180M + rtM204V + A194T in deep sequencing at a frequency of 0.3%. In the six patients classified as ETV-PR, one patient harbored rtM204I. No clones showing rtS106C + rtH126Y + rtD134E + rtL269I quadruple mutation were detected in deep sequencing. Subsequently, ETV was discontinued, and serum HBV-DNA remained undetectable up to 48 weeks in all patients., Conclusion: Patients receiving ETV plus TAF due to partial response or BTH during initial LAM or ETV administration were able to safely transition to TAF monotherapy based on nucleotide sequences of HBV pregenome RNA in the sera., (© 2024 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Histoplasmosis is caused by Histoplasma capsulatum and is prevalent in areas of the world where H. capsulatum is endemic. We herein report a patient diagnosed with HIV-1 who developed histoplasmosis from a non-H. capsulatum endemic area who experienced severe hemophagocytic syndrome due to a delayed diagnosis. The patient's symptoms emerged four years after residing in regions with a high histoplasmosis prevalence. The unrestricted administration of antifungal medication for oral candidiasis delayed the diagnosis because it improved the patient's condition. This case underscores the importance of prudent antifungal drug use in undiagnosed disseminated conditions and evaluating the travel history going back several years to facilitate a diagnosis.

The purpose of this study was to clarify the heart rate variability (HRV) transition after a single yoga program. Participants were 22 females who were healthy university students and had never practiced yoga before. They practiced yoga while recording their HRV. Heart rate (HR), high frequency (HF; 0.15-0.4 Hz) as parasympathetic and low frequency (LF; 0.04-0.15 Hz) components were extracted, and then the LF/HF ratio as sympathetic and normalized units of HF HFnu = HF/(LF + HF) as parasympathetic modulation in autonomic activity were calculated. HR and HRV indices after yoga were divided into four 5-minute periods (after 5, 10, 15, and 20 minutes) and compared before yoga. HR and LF/HF at all periods after yoga were significantly lower than before yoga (P < .01, all). HF after yoga was not significantly changed, but HFnu after 5, 10, and 15 minutes was significantly higher than before yoga (P < .01, <.01, and =.02, respectively). The short-term effects of yoga on HRV implied a decrease in sympathetic modulation and a relative increase in parasympathetic modulation. Therefore, yoga may be used as a fast-acting alternative therapy to significantly improve sympathetic activity., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Heart failure (HF) patients with complex care needs often experience exacerbations during the transitional phase as care providers and settings change. Regional collaboration aims to ensure continuity of care; however, its impact on vulnerable patients certified as needing support or care under the Japanese long-term care insurance (LTCI) system remains unclear., Methods and Results: We implemented a regional collaborative program for HF patients involving 3 pillars of transitional care with general practitioners and nursing care facilities: (1) standardized health monitoring using a patient diary and identification of exacerbation warning signs; (2) standardized information sharing among care providers; and (3) standardized HF management manuals. We evaluated outcomes within 1 year of discharge for patients hospitalized with HF and referred to other facilities for outpatient follow-up in 2017-2018 before program implementation (n=110) and in 2019-2020 after implementation (n=126). Patients with LTCI frequently received non-cardiologist follow up and care services and had a higher risk of all-cause mortality and HF readmission compared with those without LTCI (P<0.05). Program implementation was significantly associated with a greater reduction in HF readmissions among patients with LTCI compared with those without (P<0.05 for interaction), although mortality rates remained unchanged., Conclusions: A regional collaborative program significantly reduces HF readmissions in HF patients with LTCI who are at high risk of worsening HF.

The prompt initiation of stroke treatment significantly influences patient outcomes, highlighting the crucial role of prehospital triage. This study aimed to assess the implementation of the 7-Item Japan Urgent Stroke Triage (JUST-7) score by emergency medical services (EMS) in our region and its effect on emergency transportation for suspected stroke patients. Data were collected from patients suspected of having an acute stroke with a Cincinnati Prehospital Stroke Scale (CPSS) score of 1 or more who were transferred by ambulance within 24 h of symptom onset. Two prehospital stroke scales were employed during different periods: period 1 with CPSS alone (January to December 2020) and period 2 with both CPSS and JUST-7 (January 2021 to March 2023). On-scene time data were obtained from the EMS crews, and data regarding the final diagnosis of patients and their outcomes were obtained from the respective hospitals to which the patients were transferred. These data were compared between periods 1 and 2 and between the CPSS and JUST-7. The results revealed that additional evaluation with JUST-7 did not affect ambulance transport time. The CPSS+JUST-7 approach demonstrated higher specificity in identifying stroke and major artery occlusion than with the CPSS alone; however, an appropriate cut-off value needs to be considered. The JUST-7 achieved a diagnostic concordance rate of 35.9% for the most likely stroke type and 64.0% for the first two most likely types. This research emphasizes the potential of JUST-7 as a valuable addition to prehospital stroke diagnosis protocols. Its flexibility in adapting cut-off values based on regional factors and available medical resources optimizes its utility in diverse healthcare settings. The JUST-7 score is a promising tool for improving patient outcomes through prompt and accurate prehospital assessments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nishiwaki 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.)

The frequency of cardiac amyloidosis potentially present in patients with atrial fibrillation (AF) remains unclear. The purpose of this study is to determine the frequency and clinical characteristics of cardiac amyloidosis latent in AF by performing cardiac magnetic resonance imaging (MRI) in patients scheduled for AF ablation. We retrospectively analyzed 193 consecutive patients who underwent CA and cardiac MRI for atrial fibrillation. The primary endpoint of the study was the frequency of histologically confirmed cardiac amyloidosis or suspected cardiac amyloidosis [positive imaging findings on cardiac MRI strongly suspecting cardiac amyloidosis (diffuse subendocardial late gadolinium enhancement or MRI-derived extracellular volume of > 0.40)]. Among the 193 patients, 8 were confirmed or suspected cases of cardiac amyloidosis, representing a frequency of 4% (8/193 patients). Multivariate analysis identified interventricular septal thickness at end-diastole (LVSd) as an independent and significant predictor of cardiac amyloidosis (OR: 1.72, 95% CI 1.12-2.87, p = 0.020).The optimal cut-off value for IVSd was determined to be > 12.9 mm based on the Youden index. At this cut-off, the sensitivity was 75.0% (95% CI 34.9-96.8%) and the specificity was 92.3% (95% CI 87.4-95.7%), allowing for the identification of patients with definite or suspected cardiac amyloidosis. The frequency of confirmed and suspected cases of cardiac amyloidosis among patients with an IVSd > 12.9 mm was 30% (6/20 patients). In addition, prevalence of biopsy-proven cardiac amyloidosis was 10% (2/20). The prevalence of cardiac amyloidosis in atrial fibrillation patients scheduled for ablation with cardiac hypertrophy is not negligible., Competing Interests: Declarations. Conflict of interest: All authors have no conflict of interest regarding this study., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Aim: There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease., Methods: Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd-Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected., Results: The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH- primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd-Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination., Conclusion: SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases., (© 2024 Japan Society of Hepatology.)

End-stage liver disease (ESLD) is a life-threatening clinical syndrome and when complicated with infection the mortality is markedly increased. In patients with ESLD, bacterial or fungal infection can induce or aggravate the occurrence or progression of liver decompensation. Consequently, infections are among the most common complications of disease deterioration. There is an overwhelming need for standardized protocols for early diagnosis and appropriate management for patients with ESLD complicated by infections. Asia Pacific region has the largest number of ESLD patients, due to hepatitis B and the growing population of alcohol and NAFLD. Concomitant infections not only add to organ failure and high mortality but also to financial and healthcare burdens. This consensus document assembled up-to-date knowledge and experience from colleagues across the Asia-Pacific region, providing data on the principles as well as evidence-based current working protocols and practices for the diagnosis and treatment of patients with ESLD complicated by infections., (© 2024. Asian Pacific Association for the Study of the Liver.)

Arterial spin-labeling magnetic resonance imaging (ASL-MRI) is widely used for evaluating collateral development in patients with acute ischemic stroke (AIS). This study aimed to characterize the findings of multiphase ASL-MRI between embolic and atherosclerotic large vessel occlusion (LVO) to aid in the differential diagnosis. Among 982 patients with AIS, 44 who were diagnosed with acute, symptomatic, and unilateral occlusion of the horizontal segment of the middle cerebral artery (MCA) were selected and categorized into embolic stroke (ES) and atherosclerosis (AT) groups. Using ASL-MRI (postlabeling delay [PLD] of 1.5, 2.0, and 2.5 s) at admission, the ipsilateral to contralateral ratio (ICR) of the signal intensity and its time-course increasing rate (from PLD 1.5 to 2.0 and 2.5, ΔICR) were measured and compared between the two groups. The mean ICR was significantly higher in the AT group than in the ES group (AT vs. ES: 0.49 vs. 0.27 for ICR 1.5 , 0.73 vs. 0.32 for ICR 2.0 , and 0.92 vs. 0.37 for ICR 2.5 ). The ΔICR of PLD 1.5-2.0 (ΔICR 2.0 ) and 2.5 (ΔICR 2.5 ) were also significantly higher in the AT group than in the ES group (AT vs. ES: 50.9% vs. 26.3% for ΔICR 2.0 , and 92.6% vs. 42.9% for ΔICR 2.5 ). Receiver operating characteristic curves showed moderate-to-strong discriminative abilities of each ASL-MRI parameter in predicting MCA occlusion etiology. In conclusion, multiphase ASL-MRI parameters may aid in differentiating intracranial LVO etiology during the acute phase. Thus, it is applicable to AIS management.

Background: Microvascular decompression (MVD), the standard surgical approach for hemifacial spasm (HFS), can be divided into the interposition and transposition methods. Although the risk of HFS recurrence following interposition has been reported, there is limited data comparing long-term outcomes between both methods performed by a single surgeon. This study aimed to investigate the efficacy of MVD techniques on HFS by comparing surgical outcomes performed by a single surgeon in a single-center setting., Methods: A total of 109 patients who underwent MVD were analyzed and divided into the transposition (86 patients) and interposition (23 patients) groups. Postoperative outcomes at 1 month and 1 year were assessed and compared, including rates of spasm relief, complications, and recurrence., Results: Outcome assessment revealed higher rates of early spasm relief in the interposition group (66.3% vs. 100%, transposition vs. interposition, respectively, p = 0.0004), although spasm relief at 1-year postoperatively was comparable between the two groups (84.9% vs. 95.7%, transposition vs. interposition, respectively, p = 0.2929). No significant differences were observed in complication and recurrence rates. Kaplan-Meier analysis demonstrated no significant differences in the duration of spasm resolution by MVD method (p = 0.4347, log-rank test)., Conclusion: This study shows that both the transposition (Surgicel® and fibrin glue) and interposition (sponge) methods were excellent surgical techniques. The interposition method may achieve earlier spasm resolution compared to the transposition method., (© 2024. The Author(s).)

Aim: To clarify the efficacy of atezolizumab (ATZ) plus bevacizumab (BEV) as the second-line therapy for patients with unresectable hepatocellular carcinoma (HCC)., Methods: The subjects were 82 patients with HCC receiving ATZ/BEV, including 33 patients with previous therapies with molecular-targeted agents (MTA). Therapeutic efficacy was evaluated using contrast-enhanced CT according to the mRECIST., Results: The Child-Pugh scores were 5, 6,7 and 8 in 40, 35, 5 and 2 patients, respectively, and the extents of HCC progression were BCLC stage A, B and C in 3, 31 and 48 patients, respectively. Early therapeutic efficacy was evaluated in 67 patients, and percentages of patients achieving CR/PR/SD/PD until 12 weeks were 3.0%/29.9%/49.3%/17.9%, respectively, indicating ORR of 32.8% and DCR of 82.1%, The ORR was higher in MTA-naïve patients (40.5%) than in those after discontinuation of lenvatinib due to PD (7.7%, P = 0.0410), while the DCR was equivalent between both patients (83.3% vs 80.0%, P = 0.1184), and the multivariate analysis revealed previous MTA therapies with lenvatinib alone as a factor to deteriorate the ORR (HR of 4.846 (P = 0.0619)). The OS rates at 24 and 48 weeks were 86% and 72%, respectively, and the rates did not differ between MTA-naïve and MTA-experienced patients. Multivariate analyses revealed that achievement of CR, PR or SD and peripheral neutrophil/lymphocyte ratio were associated with a favorable outcome (HR of 0.124, P<0.0001 and 0.351, P = 0.0303)., Conclusions: ATZ/BEV merits consideration even for MTA-experienced patients, since the OS was equivalent to those in MTA-naïve patients despite of an unfavorable early therapeutic efficacy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yamaba 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: Evidence on transitional care for heart failure (HF) in Japan is limited. Methods and Results: We implemented a transitional HF management program in rural Japan in 2019. This involved collaboration with general practitioners or nursing care facilities and included symptom monitoring by medical/nursing staff using a handbook; standardized discharge care planning and information sharing on self-care and advance care planning using a collaborative sheet; and sharing expertise on HF management via manuals. We compared the outcomes within 1 year of discharge among patients hospitalized with HF in the 2 years before program implementation (2017-2018; historical control, n=198), in the first 2 years after program implementation (2019-2020; Intervention Phase 1, n=205), and in the second 2 years, following program revision and regional dissemination (2021-2022; Intervention Phase 2, n=195). HF readmission rates gradually decreased over Phases 1 and 2 (P<0.05). This association was consistent regardless of physician expertise, follow-up institution, or the use of nursing care services (P>0.1 for interaction). Mortality rates remained unchanged, but significantly more patients received end-of-life care at home in Phase 2 than before (P<0.05). Conclusions: The implementation of a transitional care program was associated with decreased HF readmissions and increased end-of-life care at home for HF patients in rural Japan., Competing Interests: Y.K. has received lecturer fees from AstraZeneca Co. Ltd and Boehringer Ingelhem Co., Ltd. K.Y. has received research grants from Abbott Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Biotronik Japan Inc., Japan Lifeline Co., Ltd., Fukuda Denshi; Medtronic Japan Co., Ltd., and Boston Scientific Co., Ltd., as well as lecturer fees from Otsuka Pharmaceutical Co., Ltd., Novartis, Daiichi-Sankyo Co. Ltd., and Bayer Yakuhin Ltd. The remaining authors have no conflicts of interest to declare., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

A high-resolution absorption spectrum of the S1-S0 transition of free-base phthalocyanine was observed and analyzed with improved reliability. The spectrum, with a partially resolved rotational structure, was obtained by using the buffer-gas cooling technique and a single-mode tunable laser. Our new analysis reveals that the S1←S0000 band belongs to the a-type transition, where the electronic transition moment aligns parallel to the NH-HN direction, allowing the assignment of the S1 state to 1B3u. These results agree with a prior study using supersonic expansion and are well supported by theoretical calculations. Interestingly, the rotational constant B in the S1 state, which is often smaller than that in the ground state for typical molecules, was found to be slightly larger than that in the S01Ag state. This suggests a change in the character of π bonds with the electronic excitation., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Despite advancements in coronary computed tomography angiography (CTA), challenges in positive predictive value and specificity remain due to limited spatial resolution. The purpose of this experimental study was to investigate the effect of 2nd generation deep learning-based reconstruction (DLR) on the quantitative and qualitative image quality in coronary CTA., Methods: A vessel model with stepwise non-calcified plaque was scanned using 320-detector CT. Image reconstruction was performed using four techniques: hybrid iterative reconstruction (HIR), model-based iterative reconstruction (MBIR), DLR, and 2nd generation DLR. The luminal peak CT number, contrast-to-noise ratio (CNR), and edge rise slope (ERS) were quantitatively evaluated via profile curve analysis. Two observers qualitatively graded the graininess, lumen sharpness, and overall lumen visibility on the basis of the degree of confidence for the stenosis severity using a five-point scale., Results: The image noise with HIR, MBIR, DLR, and 2nd generation DLR was 23.0, 21.0, 16.9, and 9.5 HU, respectively. The corresponding CNR (25% stenosis) was 15.5, 15.9, 22.1, and 38.3, respectively. The corresponding ERS (25% stenosis) was 203.2, 198.6, 228.9, and 262.4 HU/mm, respectively. Among the four reconstruction methods, the 2nd generation DLR achieved the significantly highest CNR and ERS values. The score of 2nd generation DLR in all evaluation points (graininess, sharpness, and overall lumen visibility) was higher than those of the other methods (overall vessel visibility score, 2.6±0.5, 3.8±0.6, 3.7±0.5, and 4.6±0.5 with HIR, MBIR, DLR, and 2nd generation DLR, respectively)., Conclusions: 2nd generation DLR provided better CNR and ERS in coronary CTA than HIR, MBIR, and previous-generation DLR, leading to the highest subjective image quality in the assessment of vessel stenosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1204/coif). D.U. reports that he has received research grants from Canon Medical Systems paid to Department of Diagnostic Radiology at Yokohama City University Graduate School of Medicine. T.T. reports that he is an employee of Canon Medical Systems Corporation. The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: 11C-methionine-PET (MET) and Thallium-201 chloride-SPECT (TL) are useful for predictive proliferation ability and tumor invasion range identification in glioma patients, however they are not always possible in any hospital or country. Our study aimed to assess whether the range of MET and Tl accumulation could be predicted from the contrast-enhanced lesions in Gadolinium (Gd)-T1 weighted magnetic resonance image in glioblastoma multiforme (GBM) patients., Methods: In 25 cases, the MET-area, TL-area, O-area where MET and TL overlap, and all accumulation area (AA-area) were measured in the same axial cross section as the Gd enhanced maximum area (Gd-area). This tracing operation was repeated with all axial fusion slices, and each volume was also measured (Gd-V, MET-V, TL-V, O-V, AA-V)., Results: The maximum accumulation distance of MET and TL beyond the Gd-area was limited to within 30 mm, 35 mm, respectively. Significant positive correlations were showed in all combinations with Gd-area: MET-area (r=0.851, P<0.0001), TL-area (r=0.955, P<0.0001), O-area (r=0.935, P<0.0001) and AA-area (r=0.893, P<0.0001), respectively. All combinations with Gd-V showed significant positive correlation: MET-V (r=0.867, P<0.0001), TL-V (r=0.952, P<0.0001), O-V (r=0.935, P<0.0001) and AA-V (r=0.897, P<0.0001), respectively., Conclusions: Approximate tumor volume Gd-V can be calculated using the formula A * B * C / 2, where A, B, and C represent the dimensions of Gd-enhanced lesion in 3 axes perpendicular to each other. The nuclide accumulation predictive table created using the obtained linear approximation functions can be used to predict the average tumor invasion range from the Gd-V without preoperative nuclear examinations.