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Hisaharu Suzuki,* Miho Nishiyama* Ophthalmology, Zengyo Suzuki Eye Clinic, Fujisawa City, Kanagawa, Japan*These authors contributed equally to this workCorrespondence: Hisaharu Suzuki, Zengyo Suzuki Eye Clinic, 1-22-11 Zengyo, Fujisawa City, Kanagawa, 251-0871, Japan, Tel +81-466-0055, Fax +81-466-0056, Email s5054@nms.ac.jpPurpose: To compare and evaluate uncorrected visual acuity (UCVA) from far to near distance for four different optical designs of intraocular lenses (IOLs), developed on the same IOL platform.Patients and Methods: In a cohort of 121 patients, who underwent uncomplicated cataract surgery in Zengyo Suzuki Eye Clinic, Japan, between June 2018 and November 2023, and who received a single-piece TECNIS OptiBlue™ platform series IOL, the following four groups were established based on the IOL implant type: ZCB00V (TE), ZXR00V (SF), DFR00V (SG), and DIB00V (EH). UCVA at 5 m, 1 m, 70 cm, 50 cm, 40 cm, and 30 cm, as well as contrast sensitivity (with and without glare), was compared at one month post-operation.Results: Regarding diffractive IOLs, patients in the SG group demonstrated significantly improved visual acuity at 5 m, 50 cm, 40 cm, and 30 cm, while those in SF group performed significantly better at 1 m. Among non-diffractive IOLs, patients in the EH group demonstrated significantly improved visual acuity scores at 1 m, 70 cm, 40 cm, and 30 cm, compared to individuals in the TE group, with comparable results between the two groups at 5 m and 50 cm. Patients in the SF and EH groups achieved similar results for visual acuity and contrast sensitivity, while those in the SG group exhibited a distinctive decrease in contrast sensitivity (with glare) relative to the other three groups.Conclusion: DFR00V seemingly provides excellent UCVA from near to far distances, aiming for spectacle independence, although at the potential cost of decreased contrast sensitivity compared to the other three IOL types. Furthermore, although ZXR00V and DIB00V differ lens structures, they may nonetheless provide similar visual quality and spectacle independence in daily life.Plain Language Summary: The study focused on the TECNIS platform, specifically the OptiBlue lens, which is available primarily in Japan. Uncorrected visual acuity (UCVA) from far to near distance was compared and evaluated among four optical designs of intraocular lenses (IOLs), developed on the same IOL platform.Keywords: postoperative visual outcome, cataract surgery, contrast sensitivity, non-diffractive lenses, continuous focus

A 63-year-old woman fell and sustained a rib fracture 2 years ago, fractures of the lumbar spine the next year and had difficulty walking. TIO due to colon cancer has been reported previously,[1] but enhanced computed tomography (CT) and colonoscopy indicated no abnormalities. We suspected a right thigh lesion, and magnetic resonance imaging revealed a mass lesion in the right femur (Figure 1C). [Extracted from the article]

Numerical health risk assessment models have been developed to describe faecal contamination of water using Escherichia coli as an indicator bacterium. Although many previously established numerical models for E. coli in aquatic environments have only considered the effects of one or two water quality parameters such as temperature and sunlight, it is difficult to simulate E. coli survival with only one or two parameters because the aquatic environment is a complex system. This study conducted a series of comparative experiments to select water quality parameters that should be preferentially considered in a numerical model for E. coli survival in lakes. The parameters considered were temperature, pH, dissolved oxygen (DO), total dissolved solids (TDS), suspended solids (SS), coexisting microbes, and light intensity. In the laboratory experiments, the survival of E. coli was observed by controlling two of these seven parameters, and the effects of these parameters on the rate of E. coli population change were statistically compared. Consequently, light intensity affected the survival of E. coli most significantly, followed by the presence of coexisting microbes, temperature, pH, and TDS. However, DO and SS had smaller effects on survival than other parameters. High-impact interactions on E. coli survival were observed between temperature and TDS and temperature and coexisting microbes. These results suggest that existing numerical models for simulating E. coli survival in lakes should be modified to consider the independent and interactive effects of multiple parameters such as sunlight, coexisting microbes, temperature, pH, and TDS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Although psychological distress is a prevalent issue among patients with amyotrophic lateral sclerosis (ALS) and can impact survival, the risk factors contributing to this distress remain insufficiently understood., Methods: Patients with ALS who completed the Profile of Mood States (POMS) between June 2017 and March 2022 were included. Participants with moderate to severe cognitive decline were excluded, resulting in the recruitment of 121 patients. The associations between POMS profiles and clinical characteristics were analyzed. Physical motor symptoms were evaluated using the Revised ALS Functional Rating Scale (ALSFRS-R) for objective measurement and the 40-item ALS Assessment Questionnaire (ALSAQ-40) for subjective assessment., Results: Our model, employing the ALSFRS-R, revealed significant factors associated with overall psychological distress, as assessed by the POMS, including upper limb symptoms, the presence of sleep apnea syndrome, older age at onset, and male sex, with an inverse association with tracheostomy. The POMS subscale scores revealed that anger and depression were significantly associated with upper limb symptoms. The second model, which employed subjective scales, yielded similar results, reinforcing the robustness of our findings. Moreover, subjective bulbar symptoms on the ALSAQ-40 were significantly associated with psychological distress, particularly in female patients., Conclusion: This study identified the main clinical characteristics significantly associated with psychological distress in patients with ALS. Our findings may be useful in developing individualized psychological management strategies for these patients., Competing Interests: Declaration of competing interest The authors have no competing interests to report., (Copyright © 2024. Published by Elsevier Inc.)

Although growth hormone (GH) and prolactin (PRL) are usually recognized as pituitary hormones, their expression is not restricted to the adenohypophysis and can also be found in extra-pituitary tissues including placenta. Furthermore, GH, PRL, and their receptors structurally belong to the cytokine family of proteins, and indeed they have remarkable pleiotropic effects. In this review, we analyzed the biological roles of GH/PRL from an evolutionary perspective. We have recognized that the biological significance of GH/PRL can be summarized as follows: cytokines (metabokines) that regulate the shift of nutrients and even of whole bodies to live in the most appropriate environment(s) for conducting growth and reproduction. In this sense, the common keyword of the two metabokines is "shift" for environmental adaptation. Considering that these metabokines flexibly changed their biological roles, GH/PRL may have played important roles during vertebrate evolution.

Background: Platinum/taxane (TC) chemotherapy with debulking surgery stays the mainstay of the treatment in ovarian cancer patients with peritoneal metastasis, and recently its novel modality, intraperitoneal carboplatin with dose-dense paclitaxel (ddTCip), was shown to have greater therapeutic impact. Nevertheless, the response varies among patients and consequent recurrence, or relapse often occurs. Discovery of therapeutic response predictor to ddTCip and/or TC therapy is eagerly awaited to improve the treatment outcome., Methods: Using datasets in 76 participants in our ddTCip study and published databases on patients received TC therapy, we first validated a total of 75 previously suggested markers, sought out more active biomarkers through the association analyses of genome-wide transcriptome and genotyping data with progression-free survival (PFS) and adverse events, and then developed multiplex statistical prediction models for PFS and toxicity by mainly using multiple regression analysis and the classification and regression tree (CART) algorithm., Results: The association analyses revealed that SPINK1 could be a possible biomarker of ddTCip efficacy, while ABCB1 rs1045642 and ERCC1 rs11615 would be a predictor of hematologic toxicity and peripheral neuropathy, respectively. Multiple regression analyses and CART algorithm finally provided a potent efficacy prediction model using 5 gene expression data and robust multiplex toxicity prediction models-CART models using a total of 4 genotype combinations and multiple regression models using 15 polymorphisms on 12 genes., Conclusion: Biomarkers and multiplex models composed here could work well in the response prediction of ddTCip and/or TC therapy, which might contribute to realize optimal selection of the key therapy., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objective: Signal transducer and activator of transcription 3 (STAT3) plays key roles in regulating cancer cell proliferation, survival, and metastasis. We aimed to determine the effects of YHO-1701, an oral STAT3 inhibitor, in ovarian cancer (OC)., Methods: We evaluated the impact of YHO-1701 on cell growth in patient-derived cells (PDCs) and OC cell lines using standard cell proliferation assays. Spheroid models derived from PDCs were assessed using three-dimensional (3D) cell viability assays. Antitumor activity was performed in SKOV3 xenograft mice treated orally administrated YHO-1701 with 20 mg/kg. Changes in STAT3 signaling were analyzed by western blotting. The molecular mechanisms of STAT3 inhibition were investigated by sequencing RNA and analyzing pathways in the SKOV3 using a small interfering RNA targeting STAT3 (STAT3 siRNA) and YHO-1701., Results: YHO-1701 inhibited the growth of OC cell lines by preventing STAT3 dimerization and decreasing the expression of its downstream signaling molecule, survivin. The growth of PDCs and spheroids obtained from patients with primary and recurrent OCs was significantly inhibited. Antitumor effect was observed in the SKOV3 xenograft mice with YHO-1701. YHO-1701 induced apoptosis in OC cells. Additionally, p53 and/or MAPK signaling pathways were upregulated in SKOV3 cells incubated with YHO-1701 and in those with STAT3 siRNA., Conclusion: Our results showed that YHO-1701 suppressed cell growth in PDCs of OC, accompanied by survivin inhibition, and a decrease in the number of peritoneal metastasis in the mice by YHO-1701, compared with those treated with control. Therefore, YHO-1701 could be a promising candidate agent for treating OC., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Introduction: KCNQ1 and KCNE1 form slowly activating delayed rectifier potassium currents (I Ks ). Loss-of-function of I Ks by KCNQ1 variants causes type-1 long QT syndrome (LQTS). Also, some KCNQ1 variants are reported to cause epilepsy. Segment 4 (S4) of voltage-gated potassium channels has several positively-charged amino acids that are periodically aligned, and acts as a voltage-sensor. Intriguingly, KCNQ1 has a neutral-charge glutamine at the third position (Q3) in the S4 (Q234 position in KCNQ1), which suggests that the Q3 (Q234) may play an important role in the gating properties of I Ks . We identified a novel KCNQ1 Q234K (substituted for a positively-charged lysine) variant in patients (a girl and her mother) with LQTS and epileptiform activity on electroencephalogram. The mother had been diagnosed with epilepsy. Therefore, we sought to elucidate the effects of the KCNQ1 Q234K on gating properties of I Ks ., Methods: Wild-type (WT)-KCNQ1 and/or Q234K-KCNQ1 were transiently expressed in tsA201-cells with KCNE1 (E1) (WT + E1-channels, Q234K + E1-channels, and WT + Q234K + E1-channels), and membrane currents were recorded using whole-cell patch-clamp techniques., Results: At 8-s depolarization, current density (CD) of the Q234K + E1-channels or WT + Q234K + E1-channels was significantly larger than the WT + E1-channels (WT + E1: 701 ± 59 pA/pF; Q234K + E1: 912 ± 50 pA/pF, p < 0.01; WT + Q234K + E1: 867 ± 48 pA/pF, p < 0.05). Voltage dependence of activation (VDA) of the Q234K + E1-channels or WT + Q234K + E1-channels was slightly but significantly shifted to depolarizing potentials in comparison to the WT + E1-channels ([V 1/2 ] WT + E1: 25.6 ± 2.6 mV; Q234K + E1: 31.8 ± 1.7 mV, p < 0.05; WT + Q234K + E1: 32.3 ± 1.9 mV, p < 0.05). Activation rate of the Q234K + E1-channels or WT + Q234K + E1-channels was significantly delayed in comparison to the WT + E1-channels ([half activation time] WT + E1: 664 ± 37 ms; Q234K + E1: 1,417 ± 60 ms, p < 0.01; WT + Q234K + E1: 1,177 ± 71 ms, p < 0.01). At 400-ms depolarization, CD of the Q234K + E1-channels or WT + Q234K + E1-channels was significantly decreased in comparison to the WT + E1-channels (WT + E1: 392 ± 42 pA/pF; Q234K + E1: 143 ± 12 pA/pF, p < 0.01; WT + Q234K + E1: 209 ± 24 pA/pF, p < 0.01) due to delayed activation rate and depolarizing shift of VDA., Conclusion: The KCNQ1 Q234K induced I Ks gain-of-function during long (8-s)-depolarization, while loss of-function during short (400-ms)-depolarization, which indicates that the variant causes LQTS, and raises a possibility that the variant may also cause epilepsy. Our data provide novel insights into the functional consequences of charge addition on the Q3 in the S4 of KCNQ1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Nakajima, Tamura, Kawabata-Iwakawa, Itoh, Hasegawa, Kobari, Harasawa, Sekine, Nishiyama, Kurabayashi, Imoto, Kaneko, Nakatani, Horie and Ishii.)

Friedreich's ataxia (FRDA) is one of the most common hereditary ataxias. It is caused by a GAA repeat in the first intron of the FXN gene, which encodes an essential mitochondrial protein. Patients suffer from progressive motor dysfunction due to the degeneration of mechanoreceptive and proprioceptive neurons in dorsal root ganglia (DRG) and cerebellar dentate nucleus neurons, especially at early disease stages. Postmortem analyses of FRDA patients also indicate pathological changes in motor cortex including in the projection neurons that give rise to the cortical spinal tract (CST). Yet, it remains poorly understood how early in the disease cortical spinal neurons (CSNs) show these alterations, or whether CSN/CST pathology resembles the abnormalities observed in other tissues affected by FXN loss. To address these questions, we examined CSN driven motor behaviors and pathology in the YG8JR FRDA mouse model. We find that FRDA mice show impaired motor skills, exhibit significant reductions in CSN functional output, and, among other pathological changes, show abnormal mitochondrial distributions in CSN neurons and CST axonal tracts. Moreover, some of these alterations were observed as early as two months of age, suggesting that CSN/CST pathology may be an earlier event in FRDA disease than previously appreciated. These studies warrant a detailed mechanistic understanding of how FXN loss impacts CSN health and functionality.

Background/aim: Gemcitabine (GEM)-based chemotherapy has been established as the core multimodal therapy for biliary tract cancer (BTC). However, the prognosis of BTC is unfavorable because of its resistance to GEM. Exosomes play important roles in the regulation of tumor progression and metastasis, immune dysregulation, and chemoresistance. This study investigated the effects of exosomes on GEM resistance in BTC., Materials and Methods: The human intrahepatic cholangiocarcinoma cell line CC-LP-1, its GEM-resistant (GR) derivative cell line CC-LP-1-GR, and the human intrahepatic cholangiocarcinoma cell lines HuCCA-1 and HuCCT1, were used. GEM resistance was examined by measuring cell viability in the presence of GEM using an MTS assay. Exosomes were isolated using ultracentrifugation and quantified using ELISA. Comprehensive expression analysis was performed using RNA sequencing. The effects of microRNAs were examined by miRNA mimic transfection., Results: The conditioned medium and exosomes derived from CC-LP-1-GR cells enhanced the GEM resistance of parental CC-LP-1 cells. In the presence of GEM, the p53 pathway was negatively enriched in CC-LP-1-GR and CC-LP-1 cells treated with exosomes from CC-LP-1-GR (rExo) compared to CC-LP-1 cells. The expression of miR-141-3p was higher in rExos than in CC-LP-1 cells. CC-LP-1 cells transfected with miR-141-3p mimic showed significantly (p<0.05) increased viability in the presence of GEM., Conclusion: A GEM-resistant human BTC cell line, CC-LP-1-GR, may acquire resistance to GEM by exosomes containing miR-141-3p., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: We evaluated the usefulness of prophylactic mini-tracheostomy (PMT) and perioperative administration of tazobactam/piperacillin (TAZ/PIPC) in high-risk patients after esophagectomy., Patients and Methods: We retrospectively studied 89 consecutive high-risk patients who underwent esophagectomy for esophageal cancer between January 2013 and December 2021. We defined patients with two or more of the following factors as high risk: age ≥70 years, performance status ≥1, respiratory dysfunction, liver dysfunction, cardiac dysfunction, renal dysfunction, diabetes mellitus, albumin <3.5 g/dl, and Brinkman index >600. Standard management was administered to the first 50 patients (standard group). PMT and TAZ/PIPC were administered to the next 39 patients (combination group). Patient characteristics and short-term outcomes were compared before and after propensity-score matching., Results: Before propensity-score matching, 24-hour urine creatinine clearance, retrosternal route, 3-field lymph node dissection, and open abdominal approach were more common, postoperative pneumonia (13% vs. 36%, p=0.045) and complications of grade ≥3b (2.6% vs. 22%, p=0.01) were less frequent, and the postoperative hospital stay was shorter (median: 23 vs. 28 days, p=0.022) in the combination group than in the standard group. In propensity-score matching, patient characteristics, except for 24-h creatinine clearance and reconstructive route, were matched for 23 paired patients. Postoperative pneumonia (8.7% vs. 39%, p=0.035) and complications of grade ≥3b (0% vs. 26%, p=0.022) were less frequent and postoperative hospital stay was shorter (median: 22 vs. 25 days, p=0.021) in the combination group than in the standard group., Conclusion: PMT with TAZ/PIPC can potentially prevent postoperative pneumonia in high-risk patients after esophagectomy., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Antimicrobials are used on livestock farms to treat and prevent infectious animal diseases and to promote the growth of livestock. We monitored the prevalence of antibiotic-resistant Escherichia coli (AR-EC) isolates from beef cattle (BC) and dairy cows (DCs) on a livestock farm in Yamagata, Japan. Fecal samples from 5 male BC and 10 male DCs were collected monthly from October 2022 to November 2023. In total, 152 and 884 E. coli isolates were obtained from the BC and DC fecal samples, respectively. Notably, 26 (17.1%) and 29 (3.3%) E. coli isolates in the BC and DC groups, respectively, were resistant to at least one antibiotic. The resistance rates to tetracycline, ampicillin, gentamicin, and chloramphenicol of the isolates were significantly higher than those to the other antimicrobials. The tetracycline resistance genes tetA (70.6%) in DCs and tetB (28%) in BC were identified, along with the bla TEM gene in ampicillin-resistant isolates (BC: 84.2%, DCs: 42.8%). Despite significant variations in the monthly detection rates of AR-EC isolated from BC and DCs throughout the sampling period, the judicious use of antimicrobials reduced the occurrence of AR-EC in both BC and DCs, thereby minimizing their release into the environment.

The present study aimed to identify preoperative and perioperative risk factors for postoperative infectious complications in older patients with gastric cancer. The present retrospective study included 504 patients with gastric cancer aged >65 years who underwent radical gastrectomy. After determining the cutoff values for various perioperative factors in the receiver operating characteristic curve analysis, preoperative and perioperative risk factors for the development of infectious complications after gastrectomy were examined using logistic regression analysis. Of the 504 patients who underwent gastrectomy, 95 (18.8%) developed infectious complications of grade II-V based on the Clavien-Dindo classification. In an analysis restricted to preoperative factors, male sex, low prognostic nutritional index, high visceral fat area and total gastrectomy were independent risk factors for infectious complications after gastrectomy. Among all perioperative factors, a low prognostic nutritional index and long operative duration were identified as independent risk factors for infectious complications after gastrectomy. The patients were divided into five groups according to the number of positive preoperative risk factors for infectious complications, and the incidence of infectious complications differed among the five groups (0 factors, 6.7%; 1 factor, 10.4%; 2 factors, 18.9%; 3 factors, 27.8%; and 4 factors, 47.6%; P<0.001). Older patients with gastric cancer who have a number of preoperative risk factors require careful consideration of the indication for gastrectomy and a shorter operative time to reduce infectious complications., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Iida et al.)

Currently available numerical models that describe the fecal contamination of aquatic environments using Escherichia coli as an indicator bacterium did not consider its survival in sediments. We conducted a series of comparative experiments to reveal the independent and interactive effects of sediment factors, including temperature, pH, water-extractable total dissolved solids (TDSs), coexisting microbes, and sampling sites, in lake environments on E. coli survival. In experiments, E. coli survival was observed by controlling any two factors at a time. Consequently, the decrease in pH and presence of coexisting microbes enhanced E. coli die-off, whereas the addition of water-extractable TDSs promoted its growth. To select factors to be considered for modelling E. coli survival in sediments, the independent effects of each factor and the interaction effect of the two factors were statistically compared based on their effect sizes (η 2 ). As a result, pH (η 2 = 59.5-89.0%) affected E. coli survival most significantly, followed by coexisting microbes (1.7-48.4%). Among the interactions affecting E. coli survival, including pH or coexisting microbes-which had larger independent effects-relatively larger statistically significant interactions were observed between pH and coexisting microbes (31.1%), coexisting microbes and water-extractable TDSs (85.4%), and coexisting microbes and temperature (26.4%).

Background: The docking-free design of the Japanese Hinotori surgical robotic system allows the robotic arm to avoid trocar grasping, thereby minimising excessive abdominal wall stress. The aim of this study was to evaluate the safety and efficacy of robotic-assisted radical prostatectomy (RARP) using the Hinotori system and to explore the potential contribution of its docking-free design to postoperative pain reduction., Methods: This study reviewed the clinical records of 94 patients who underwent RARP: 48 patients in the Hinotori group and 46 in the da Vinci Xi group., Results: Hinotori group had significantly longer operative and console times (p = 0.030 and p = 0.029, respectively). Perioperative complications and oncologic outcomes did not differ between the two groups. On postoperative day 4, the rate of decline from the maximum visual analogue scale score was marginally significant in the Hinotori group (p = 0.062)., Conclusions: The docking-free design may contribute to reducing postoperative pain., (© 2024 John Wiley & Sons Ltd.)

Meiosis is a key step during germ cell differentiation, accompanied by the activation of thousands of genes through germline-specific chromatin reorganization. The chromatin remodeling mechanisms underpinning early meiotic stages remain poorly understood. Here we focus on the function of one of the major autism genes, CHD8, in spermatogenesis, based on the epidemiological association between autism and low fertility rates. Specific ablation of Chd8 in germ cells results in gradual depletion of undifferentiated spermatogonia and the failure of meiotic double-strand break (DSB) formation, leading to meiotic prophase I arrest and cell death. Transcriptional analyses demonstrate that CHD8 is required for extensive activation of spermatogenic genes in spermatogonia, necessary for spermatogonial proliferation and meiosis. CHD8 directly binds and regulates genes crucial for meiosis, including H3K4me3 histone methyltransferase genes, meiotic cohesin genes, HORMA domain-containing genes, synaptonemal complex genes, and DNA damage response genes. We infer that CHD8 contributes to meiotic DSB formation and subsequent meiotic progression through combined regulation of these meiosis-related genes. Our study uncovers an essential role of CHD8 in the proliferation of undifferentiated spermatogonia and the successful progression of meiotic prophase I., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Glutamate is an essential biological compound produced for various therapeutic and nutritional applications. The current glutamate production process requires a large amount of ammonium, which is generated through the energy-consuming and CO 2 -emitting Haber-Bosch process; therefore, the development of bio-economical glutamate production processes is required. We herein developed a strategy for glutamate production from aerial nitrogen using the nitrogen-fixing bacterium Klebsiella oxytoca. We showed that a simultaneous supply of glucose and citrate as carbon sources enhanced the nitrogenase activity of K. oxytoca. In the presence of glucose and citrate, K. oxytoca strain that was genetically engineered to increase the supply of 2-oxoglutarate, a precursor of glutamate synthesis, produced glutamate extracellularly more than 1 g L -1 from aerial nitrogen. This strategy offers a sustainable and eco-friendly manufacturing process to produce various nitrogen-containing compounds using aerial nitrogen., (© 2024. The Author(s).)

Introduction: This study was performed to evaluate the differences in the perioperative results, renal function, and incidence of hydronephrosis over time between the use of Bricker anastomosis and Wallace anastomosis for robot-assisted intracorporeal ileal conduit urinary diversion (RICIC)., Methods: Fifty-five patients who underwent RICIC at two institutions were evaluated (Bricker, n = 23; Wallace, n = 32). We investigated changes in estimated glomerular filtration rate and hydronephrosis before surgery and at 3, 6, and 12 months after surgery., Results: The patients in the Bricker group were significantly older than those in the Wallace group. The urinary diversion time was significantly longer in the Bricker group. No significant difference in postoperative renal function was observed. Additionally, no significant difference was observed in the incidence of postoperative hydronephrosis. However, the incidence of right hydronephrosis tended to be high overall, especially in the Wallace group. No patients in either group required repair surgery or ureteral stent placement., Conclusions: In patients undergoing RICIC, there was no difference in postoperative renal function or the incidence of hydronephrosis between Wallace and Bricker anastomosis. Symptomatic hydronephrosis was not observed in either group. The present study showed that each method was equally effective and safe., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

A 59-year-old man was admitted to our hospital with hyponatremia. An endocrine examination indicated panhypopituitarism, and magnetic resonance imaging revealed a mass-like lesion in the pituitary gland. Sinus endoscopy revealed a fungal mass in the sphenoid sinus, and the patient was diagnosed with hypopituitarism due to aspergillosis of the central nervous system (CNS). The patient's hyponatremia resolved with hydrocortisone replacement. Although the right internal carotid artery was eventually occluded, antifungal medications were administered for the aspergillosis, and the patient's general condition improved. The patient's CNS lesions have remained under control since discharge. This is the first case to suggest that ACTH secretion may be relatively preserved in Aspergillus-induced hypopituitarism.

CHD8 is an ATP-dependent chromatin-remodeling factor encoded by the most frequently mutated gene in individuals with autism spectrum disorder (ASD). Although many studies have examined the consequences of CHD8 haploinsufficiency in cells and mice, few have focused on missense mutations, the most common type of CHD8 alteration in ASD patients. We here characterized CHD8 missense mutations in ASD patients according to six prediction scores and experimentally examined the effects of such mutations on the biochemical activities of CHD8, neural differentiation of embryonic stem cells, and mouse behavior. Only mutations with high prediction scores gave rise to ASD-like phenotypes in mice, suggesting that not all CHD8 missense mutations detected in ASD patients are directly responsible for the development of ASD. Furthermore, we found that mutations with high scores cause ASD by mechanisms either dependent on or independent of loss of chromatin-remodeling function. Our results thus provide insight into the molecular underpinnings of ASD pathogenesis caused by missense mutations of CHD8., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Lymphedema, resulting from impaired lymphatic drainage, causes inflammation, fibrosis and tissue damage leading to symptoms such as limb swelling and restricted mobility. Despite various treatments under exploration, no standard effective therapy exists. Here a novel technique using the pyro-drive jet injection (PJI) was used to create artificial clefts between collagen fibers, which facilitated the removal of excess interstitial fluid. The PJI was used to deliver a mixture of lactated Ringer's solution and air into the tail of animals with secondary skin edema. Edema levels were assessed using micro-CT scanning. Histopathological changes and neovascularization were evaluated on the injury-induced regenerative tissue. Regarding tissue remodeling, we focused on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF)-C. PJI markedly diminished soft tissue volume in the experimental lymphedema animals compared to the non-injected counterparts. The PJI groups exhibited a significantly reduced proportion of inflammatory granulation tissue and an enhanced density of lymphatic vessels and α-smooth muscle actin (αSMA)-positive small vessels in the fibrous granulation tissue compared to the controls. In addition, PJI curtailed the prevalence of CTGF- and VEGF-C-positive cells in regenerative tissue. In a lymphedema animal model, PJI notably ameliorated interstitial edema, promoted lymphatic vessel growth, and bolstered αSMA-positive capillaries in fibrous granulation tissue. PJI's minimal tissue impact post-lymph node dissection indicates significant potential as an early, standard preventative measure. Easily applied in general clinics without requiring specialized training, it offers a cost-effective and highly versatile solution to the management of lymphedema., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

Mycoplasma genitalium (MG) is an emerging sexually transmitted infection, which appears to be a cause of urethritis and cervicitis and has been associated with pelvic inflammatory disease (PID), epididymitis, proctitis, infertility, complications during pregnancy, and human immunodeficiency virus (HIV) transmission. Three Food and Drug Administration (FDA) approved tests are available. Testing should be focused to avoid inappropriate antibiotic use. The Center of Disease Control and Prevention (CDC) guidelines recommend testing for persistent male urethritis, cervicitis, and proctitis and state that testing should be considered in cases of PID. Testing is also recommended for sexual contacts of patients with MG. Testing is not recommended in asymptomatic patients, including pregnant patients, who do not have a history of MG exposure. Although resistance-guided therapy is recommended, there are currently no FDA approved tests for MG macrolide resistance, and tests are not widely available in the United States. The CDC recommends 2-step treatment with doxycycline followed by azithromycin or moxifloxacin. Moxifloxacin is recommended if resistance testing is unavailable or testing demonstrates macrolide resistance.., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to clarify the panoramic image differences of cleft alveolus patients with or without a cleft palate, with emphases on the visibility of the line formed by the junction between the nasal septum and nasal floor (the upper line) and the appearances of the maxillary lateral incisor., Materials and Methods: Panoramic radiographs of 238 patients with cleft alveolus were analyzed for the visibility of the upper line, including clear, obscure or invisible, and the appearances of the maxillary lateral incisor, regarding congenital absence, incomplete growth, delayed eruption and medial inclination. Differences in the distribution ratio of these visibility and appearances were verified between the patients with and without a cleft palate using the chi-square test., Results: There was a significant difference in the visibility distribution of the upper line between the patients with and without a cleft palate (p<0.05). In most of the patients with a cleft palate, the upper line was not observed. In the unilateral cleft alveolus patients, the medial inclination of the maxillary lateral incisor was more frequently observed in patients with a cleft palate than in patients without a cleft palate., Conclusion: Two differences were identified in panoramic appearances. The first was the disappearance (invisible appearance) of the upper line in patients with a cleft palate, and the second was a change in the medial inclination on the affected side maxillary lateral incisor in unilateral cleft alveolus patients with a cleft palate., Competing Interests: Conflicts of Interest: None, (Copyright © 2024 by Korean Academy of Oral and Maxillofacial Radiology.)

Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sometimes triggers acute encephalopathy as a serious neurological complication in children. We previously reported the clinico-radiological findings of SARS-CoV-2-associated encephalopathy. The advent of the SARS-CoV-2 omicron variant led to a marked increase in pediatric patients with coronavirus disease 2019 (COVID-19); however, epidemiological changes with acute encephalopathy according to the emergence of SARS-CoV-2 have not yet been documented. Therefore, the present study investigated epidemiological differences in SARS-CoV-2-associated encephalopathy during the BA.1/BA.2 and BA.5 predominant periods and also between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy., Methods: We conducted a nationwide survey of SARS-CoV-2-associated encephalopathy in Japanese children between June and November 2022. We compared the present results during the BA.5 predominant period and previous findings during the BA.1/BA.2 predominant period. We also compared the clinico-radiological syndromes of encephalopathy between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy., Results: Although many patients with SARS-CoV-2-associated encephalopathy in the BA.5 predominant period had seizures as their initial symptoms, no significant differences were observed in the clinical features. Patients with SARS-CoV-2-associated encephalopathy had worse outcomes than those with non-SARS-CoV-2-associated encephalopathy (p-value = 0.003). Among 103 patients with SARS-CoV-2-associated encephalopathy, 14 (13.6%) had severe types of acute encephalopathy, namely, encephalopathy with acute fulminant cerebral edema (AFCE) and hemorrhagic shock and encephalopathy syndrome (HSES). Also, 28 (27.2%) patients with SARS-CoV-2-associated encephalopathy had poor outcome: severe neurological sequelae or death. Ninety-five patients (92.2%) were not vaccinated against SARS-CoV-2., Conclusions: In SARS-CoV-2-associated encephalopathy, high percentages of AFCE and HSES can result in poor outcomes., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Although the causes of neurodevelopmental disorders remain unknown, several environmental risk factors have attracted considerable attention. We conducted a retrospective, longitudinal, population-based cohort study using data from infant health examinations of children born to mothers with pregnancies between April 1, 2014 and March 31, 2016 in Kobe City to identify the perinatal factors associated with neurodevelopmental referrals in 3-year-old children. There were 15,223 and 1283 children in the normal and referral groups, respectively. Neurodevelopmental referrals at the health checkup for 3-year-old children were significantly associated with the lack of social support during pregnancy (adjusted odds ratio [aOR] 1.99, 99% CI 1.14-3.45, p = 0.001), history of psychiatric consultation (aOR 1.56, 99% CI 1.10-2.22, p = 0.001), no social assistance post-delivery (aOR 1.49, 99% CI 1.03-2.16, p = 0.006), Edinburgh Post-natal Depression Scale (EPDS) score ≥ 9 (aOR 1.36, 99% CI 1.01-1.84, p = 0.008), infant gender (male) (aOR 2.51, 99% CI 2.05-3.06, p < 0.001), and cesarean delivery (aOR 1.39, 99% CI 1.11-1.75, p < 0.001). In conclusion, this exploratory study in the general Japanese population identified six perinatal factors associated with neurodevelopmental referrals in 3-year-old children: infant gender (male), cesarean section, maternal history of psychiatric consultation, EPDS score ≥ 9, lack of social support during pregnancy, and no social assistance post-delivery., (© 2024. The Author(s).)

Background/aim: In gastric cancer, accurate determination of human epidermal growth factor receptor type 2 (HER2) status is crucial for treatment decision-making. However, the optimal formalin fixation time of gastric cancer specimens for HER2 status determination remains unestablished. Here, we investigated real-world data on formalin overfixation and its effect on HER2 status determination in gastric cancer., Patients and Methods: We comprehensively analyzed HER2 testing results in 228 gastric cancer specimens, including those subjected to formalin overfixation. Subsequently, we divided 52 resected specimens of advanced gastric cancer into three groups and studied the effects of short-term (6-72 h) and long-term (1 and 2 weeks) fixation on HER2 status determination using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH)., Results: A total of 21.5% (49/228) of the specimens were HER2-positive, whereas 78.5% (179/228) were negative. Among the HER2-negative specimens, no biopsies were overfixed, whereas 12.5% (9/72) of the surgical resection specimens were overfixed. The HER2 status of the 6-72-h group was 82.7% and 76.9% identical to that of the 1- and 2-week groups, when determined using IHC, and 73.1% and 36.5%, when determined using FISH, respectively. However, HER2 determination was not feasible in 26.9% and 63.5% of the specimens in the 1- and 2-week groups, respectively., Conclusion: Formalin overfixation may hinder the determination of HER2 status and should be avoided in gastric cancer sample preparation., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

In verapamil-sensitive left posterior fascicular ventricular tachycardia (LPF-VT), radiofrequency catheter ablation (RFA) is performed targeting mid-to-late diastolic potential (P1) and presystolic potential (P2) during tachycardia. This study included four patients who had undergone electrophysiological study (EPS) and pediatric patients with verapamil-sensitive LPF-VT who had undergone RFA using high-density three-dimensional (3D) mapping. The included patients were 11-14 years old. During EPS, right bundle branch block and superior configuration VT were induced in all patients. VT mapping was performed via the transseptal approach. P1 and P2 during VT were recorded in three of the four patients. All patients initially underwent RFA via the transseptal approach. In three patients, P1 during VT was targeted, and VT was terminated. The lesion size indices in which VT was terminated were 4.6, 4.6, and 4.7. For one patient whose P1 could not be recorded, linear ablation was performed perpendicularly in the area where P2 was recorded during VT. Among the three patients in whom VT was terminated, linear ablation was performed in two to eliminate the ventricular echo beats. In all patients, VT became uninducible in the acute phase and had not recurred 8-24 months after RFA. High-density 3D mapping with an HD Grid Mapping Catheter allows recording of P1 and P2 during VT and may improve the success rate of RFA in pediatric patients with verapamil-sensitive LPF-VT., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Using treated wastewater (TWW) resources in agriculture is a major pathway for disseminating nanoparticles. Copper-oxide nanoparticles (nCuO) offer potential benefits, but their presence in the environment poses risks to agricultural and environmental sustainability. This study examined soil microbial transformations and the composition of leachate dissolved organic matter (DOM) of paddy soils irrigated with nCuO-contaminated TWW at different concentrations (T2: 0.02 mgL -1 , T3: 0.2 mgL -1 , T4: 2.0 mgL -1 ) and examined the differences in Cu source (T5: 0.2 mgL -1 CuSO 4 ). Results showed negative impacts on the absolute microbial abundance with up to 46 % reduction relative to the control treatment (T1). Changes in relative abundance of specific microbes at the genus level deviated from the corresponding phyla. Acidobacteria, Actinobacteria, Chloroflexi, and Verrucomicrobia phyla increased in the surface (0-3 cm) and subsurface (3-15 cm) layers responding differently to nCuO. In the 0-3 cm layer, Nitrospirae, Euryarchaeota, and Crenarchaeota increased, but only Dechloromonas genus from Proteobacteria increased with increasing nCuO. No significant variations were observed in the DOM composition, except in T4, which had a significantly low content of dissolved organic carbon (DOC), total dissolved nitrogen, and terrestrial humic-like and protein-like components. Ninety-eight distinct genera were identified, of which 44%, including 15 bacteria and two archaea, varied between the surface and subsurface, among treatments, and significantly correlated with more DOM parameters in the subsurface. T4 had the highest microbial diversity in the 0-3 layer, and Cu treatments slightly increased the diversity index in the subsurface. Moreover, the effects differed by Cu source, with T3 showing 10 % more reduction in the subsurface and 17 % less reduction in the surface than T5. The variable microbial responses to nCuO and their strong correlations with DOM highlight the need to consider the potential consequences of low nCuO concentrations on biogeochemical cycles., 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 © 2023 Elsevier Ltd. All rights reserved.)

Membrane transporters expressed in the choroid plexus (CP) are involved in the transport of substances between the blood and cerebrospinal fluid (CSF). Carnitine/organic cation transporter 1 (OCTN1, also known as SLC22A4) is expressed in rodent CP; however, its specific roles in blood-CSF transport remain unclear. Therefore, in this study, we aimed to evaluate the potential role of OCTN1 in the elimination of substances from CSF. Tritium-labeled ergothioneine ([ 3 H]ERGO), a typical in vivo substrate of OCTN1, was injected into the lateral ventricles of wild-type and octn1 gene knockout (octn1 -/- ) mice. Clearance of [ 3 H]ERGO from CSF was higher than that of the bulk flow marker, [ 14 C]mannitol, in wild-type mice. However, [ 3 H]ERGO clearance was significantly lower in octn1 -/- mice than in wild-type mice. Furthermore, OCTN1 expression in CP was determined via immunohistochemical analysis. CP/CSF ratio of [ 3 H]ERGO was significantly lower in octn1 -/- mice than in wild-type mice. These results suggest that OCTN1 is functionally expressed in CP and involved in the elimination of ERGO from CSF in mice.

Cardiac ryanodine receptor (RyR2) gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Conversely, RyR2 loss-of-function mutations cause a new disease entity, termed calcium release deficiency syndrome (CRDS), which may include RYR2-related long QT syndrome (LQTS). Importantly, unlike CPVT, patients with CRDS do not always exhibit exercise- or epinephrine-induced ventricular arrhythmias, which precludes a diagnosis of CRDS. Here we report a boy and his father, who both experienced exercise-induced cardiac events and harbor the same RYR2 E4107A variant. In the boy, an exercise stress test (EST) and epinephrine provocation test (EPT) did not induce any ventricular arrhythmias. QTc was slightly prolonged (QTc: 474 ms), and an EPT induced QTc prolongation (QTc-baseline: 466 ms, peak: 532 ms, steady-state: 527 ms). In contrast, in his father, QTc was not prolonged (QTc: 417 ms), and neither an EST nor EPT induced QTc prolongation. However, an EST induced multifocal premature ventricular contraction (PVC) bigeminy and bidirectional PVC couplets. Thus, they exhibited distinct clinical phenotypes: the boy exhibited LQTS (or CRDS) phenotype, whereas his father exhibited CPVT phenotype. These findings suggest that, in addition to the altered RyR2 function, other unidentified factors, such as other genetic, epigenetic, and environmental factors, and aging, may be involved in the diverse phenotypic manifestations. Considering that a single RYR2 variant can cause both CPVT and LQTS (or CRDS) phenotypes, in cascade screening of patients with CPVT and CRDS, an EST and EPT are not sufficient and genetic analysis is required to identify individuals who are at increased risk for life-threatening arrhythmias.

Type II polyketide synthases (PKSs) normally synthesize polycyclic aromatic compounds in nature, and the potential to elaborate further diverse skeletons was recently revealed by the discovery of a polyene subgroup. Here, we show a type II PKS machinery for the biosynthesis of a five-membered nonaromatic skeleton contained in the nonproteinogenic amino acid cispentacin and the plant toxin coronatine. We successfully produce cispentacin in a heterologous host and reconstruct its biosynthesis using seven recombinant proteins in vitro. Biochemical analyses of each protein reveal the unique enzymatic reactions, indicating that a heterodimer of type II PKS-like enzymes (AmcF-AmcG) catalyzes a single C 2 elongation as well as a subsequent cyclization on the acyl carrier protein (AmcB) to form a key intermediate with a five-membered ring. The subsequent reactions, which are catalyzed by a collection of type II PKS-like enzymes, are also peculiar. This work further expands the definition of type II PKS and illuminates an unexplored genetic resource for natural products., (© 2023. The Author(s).)

The patient was a 75-year-old man who had undergone potentially curative surgery for Stage Ⅲb rectal cancer followed by resection of liver metastases. Two years after the resection of liver metastases, lung and remnant liver metastases were found. He received chemotherapy for unresectable metastatic tumors. Based on the findings of molecular and pathological examinations(RAS: wild type; BRAF: wild type; MSI: negative; HER2: negative), the following chemotherapy regimens were administered: first-line, FOLFIRI plus panitumumab(PANI); second-line, mFOLFOX6; third-line, trifluridine/tipiracil; fourth- line, regorafenib. After fourth-line treatment, he was judged to have disease progression due to the increase in his lung and liver metastases and the elevation of tumor markers. All standard regimens were refractory, but the Eastern Cooperative Oncology Group performance status was zero and a liquid biopsy for RAS still showed wild type. Therefore, rechallenge therapy with anti-epidermal growth factor receptor(EGFR)drugs, cetuximab(CET)and irinotecan(IRI), was administered 13 months after the final course of FOLFIRI plus PANI treatment. After 4 courses of CET plus IRI, the size of the 2 metastatic tumors markedly decreased and his tumor marker levels normalized.

Soil microbial communities control biogeochemical processes, nutrient cycling, and organic carbon storage and release in wetlands, which are influenced by flooding. To predict soil nutrient function in wetland ecosystems, understanding the effect of flooding on soil biogeochemical cycling and energy flux, including soil properties, dissolved organic matter (DOM), and microbial communities is essential. This study investigated how different flood durations (1, 3, 8, 16, and 30 d) affect the interactions between physicochemical properties and bacterial communities in a river wetland. The DOM composition was measured using ultraviolet/visible spectrophotometry coupled with fluorescence spectroscopy, and the bacterial communities were identified using 16S rRNA sequencing. Simpson's diversity index varied from 0.92 to 0.94, indicating high bacterial diversity throughout the treatments; the highest and lowest bacterial diversities were found at 1 and 8 flooding days, respectively. The abundance of Desulturomonadales, Clostridiales, Bacteroidales, and Gaiellales was positively correlated with pH, electrical conductivity, water-extractable dissolved organic carbon (WEOC), and water-extractable total dissolved nitrogen (TDN) but negatively correlated with dissolved oxygen (DO) and soil organic matter (SOM), suggesting complex interactions among these factors in response to flooding. Structural equation model revealed that flooding directly increased TDN but indirectly increased WEOC through increasing soil pH; and directly decreased DO and SOM, leading to decreases in total protein-like fraction. Three significant pathways were identified, showing the impacts of flooding on bacterial diversity: (1) flood duration decreased DO, resulting in decreased bacterial diversity; (2) flood duration decreased SOM, leading to increased bacterial diversity; and (3) flood duration decreased DO and SOM, leading to increased bacterial diversity via decreased total protein-like fraction. This study indicated that prolonged flooding has both positive and negative impacts on bacterial diversity, depending on environmental factors. It highlights the importance of flooding in shaping soil bacterial communities, with implications for nutrient cycling and carbon storage in wetlands., 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 © 2023 Elsevier B.V. All rights reserved.)