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Traumatic brain injury is the most common cause of death and disability in young people including sport athletes and soldiers, people under 45 years of age in the industrialized countries, representing a growing health problem in developing countries, as well as in aging communities. Treatment of the latter is a serious challenge for modern medicine. This type of injury leads to many kinds of disorders and, quite often, to disability. These issue require development of new methods for brain trauma treatment. The new approach to brain trauma treatment was studied in murine experiments. In particular, sodium salt of deoxyribonucleic acid (DNA) was used. This preparation is a drug known as a mixture of peptides with immunomodulatory effect which is widely used for different kinds of therapy. Derinat, a sodium salt of DNA, isolated from the caviar of Russian sturgeon, is a proven immunomodulator for treatment of diseases associatd with reactive oxygen species (ROS), including brain ischemia-reperfusion (IR) injury. Here we show that treatment with Derinat exert neuroprotective, anti-oxidative, and anti-inflammatory effects in experimental model of traumatic brain injury (TBI) in rats. Intraperitoneal injection of Derinat several times over 3 days after TBI showed less pronounced damage of the injured brain area. Immunohistochemical study showed that the Derinat-induced morphological changes of microglia in cerebral cortex and hippocampus 7 days after TBI. TBI-induced accumulation of 8-oxoguanine (8-oxoG), the marker of oxidative damage, was significantly attenuated by Derinat administration, both on 7th and 14th day after TBI. To investigate cellular mechanism of anti-inflammatory effects, the primary cultures of murine microglia supplied with ATP (50 M and 1 mM), as a substance released at injured site, were used to mimic the in vitro inflammatory response. Derinate treatment caused an increase of glial levels of mRNAs encoding neurotrophic factor (GDNF) and nerve growth factor (NGF) in the presence of ATP, whereas tissue plasminogen activator (tPA) mRNA was inhibited by ATP with or without Derinat. Interleukin-6 (IL-6) mRNA expression was not affected by ATP but was increased by Derinat. Both mRNA and protein levels of ATP-induced TNFα production were significantly inhibited by Derinat. These results partially contribute to understanding mechanisms of immunomodulatory effects of DNA preparations in traumatic brain injury.

Myxobacteria are non-photosynthetic bacteria distinguished among prokaryotes by a multicellular stage in their life cycle known as fruiting bodies that are formed in response to nutrient deprivation and stimulated by light. Here, we report an entrained, rhythmic pattern of Myxococcus macrosporus fruiting bodies, forming consistently spaced concentric rings when grown in the dark. Light exposure disrupts this rhythmic phenotype, resulting in a sporadic arrangement and reduced fruiting-body count. M. macrosporus genome encodes a red-light photoreceptor, a bacteriophytochrome (BphP), previously shown to affect the fruiting-body formation in the related myxobacterium Stigmatella aurantiaca. Similarly, the formation of M. macrosporus fruiting bodies is also impacted by the exposure to BphP-specific wavelengths of light. RNA-Seq analysis of M. macrosporus revealed constitutive expression of the bphP gene. Phytochromes, as light-regulated enzymes, control many aspects of plant development including photomorphogenesis. They are intrinsically correlated to circadian clock proteins, impacting the overall light-mediated entrainment of the circadian clock. However, this functional relationship remains unexplored in non-photosynthetic prokaryotes. Genomic analysis unveiled the presence of multiple homologs of cyanobacterial core oscillatory gene, kaiC, in various myxobacteria, including M. macrosporus, S. aurantiaca and M. xanthus. RNA-Seq analysis verified the expression of all kaiC homologs in M. macrosporus and the closely related M. xanthus, which lacks bphP genes. Overall, this study unravels the rhythmic growth pattern during M. macrosporus development, governed by environmental factors such as light and nutrients. In addition, myxobacteria may have a time-measuring mechanism resembling the cyanobacterial circadian clock that links the photoreceptor (BphP) function to the observed rhythmic behavior., (© 2024. The Author(s).)

Background: Chemotherapy-induced nausea and vomiting (CINV) commonly affects patient quality of life and the overall effectiveness of chemotherapy. This study aimed to evaluate whether adding neurokinin-1 receptor antagonists (NK1RAs) to 5-hydroxytryptamine-3 receptor antagonists (5-HT 3 RAs) and corticosteroids provides clinically meaningful benefits in preventing CINV in patients receiving moderately emetogenic chemotherapy (MEC)., Methods: We conducted a systematic review of PubMed, Cochrane Library, and Ichushi-Web to identify clinical studies evaluating NK1RAs combined with 5-HT 3 RAs and dexamethasone for managing CINV in MEC. The endpoints were complete response (CR), complete control (CC), total control (TC), adverse events, and costs. The data were analyzed using a random effects model., Results: From 142 articles identified, 15 randomized controlled trials (RCTs), involving 4,405 patients, were included in the meta-analysis. Approximately 60% of the patients received carboplatin (CBDCA)-based chemotherapy. The meta-analysis showed that triplet antiemetic prophylaxis with NK1RA was significantly more effective for achieving CR than doublet prophylaxis in each phase. Regarding CC, the triplet antiemetic prophylaxis was significantly more effective than the doublet in the overall (risk difference [RD]: 0.11, 95% confidence interval [CI]: 0.06-0.17) and delayed (RD: 0.08, 95% CI: 0.02-0.13) phases. For TC, no significant differences were observed in any phase. Adding NK1RA did not cause adverse events., Conclusions: Adding NK1RA to CBDCA-based chemotherapy has shown clinical benefits. However, the clinical benefits of NK1RA-containing regimens for overall MEC have not yet been established and require RCTs that exclusively evaluate MEC regimens other than CBDCA-based chemotherapy., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

The increasing prevalence of AmpC- and extended-spectrum β-lactamase (ESBL)- producing food pathogens is a serious public health concern. AmpC- and ESBL-producing Salmonella species pose a high risk of food contamination., Aims: This study aimed to investigate changes in the prevalence of Salmonella among food handlers in Japan from 2006 to 2021 using 100 randomly selected isolates from 2006, 2012, 2018, and 2021 with different serotypes and antimicrobial resistance patterns., Methods and Results: The average Salmonella isolation rate was 0.070% (19,602/27,848,713). Serotyping revealed that the most common serotypes were Enteritidis in 2006, Infantis in 2012, Agoueve/Cubana in 2018, and Schwarzengrund in 2021. Antimicrobial susceptibility testing showed that Salmonella isolates exhibited the highest resistance to streptomycin (< 40%), followed by tetracycline (< 20%-40%). Moreover, 6% of the Salmonella isolates produced cephalosporinases with the blaCMY-2, blaCTX-M-14, and blaTEM genes. The annual incidence of cephalosporin resistance has increased. Plasmid conjugation assays revealed that cephalosporin-resistant Salmonella spp. transmitted their resistance to Escherichia coli. Additionally, plasmid genome analysis showed that the insertion sequence IS26 was encoded in the upstream and downstream regions of blaCTX-M-14 and qnrS1 in the IncHI1 plasmid, which could be transmitted to other bacteria., Conclusions: The tested Salmonella isolates showed high resistance to specific antibiotics, with differences in resistance depending on the serotype. Further increase and spread of transmissible cephalosporin-resistant strains should be noted., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

RECK is a candidate tumor suppressor gene isolated as a gene that induces flat reversion in a cell line transformed by the KRAS oncogene. Since RECK knockout mice die in utero, they are not suitable for studying the effects of RECK on tumor formation. In this study, we found an increased incidence of spontaneous pulmonary adenomas in mice with reduced RECK expression (RECK-Hypo mice). To evaluate the effects of RECK expressed by either tumor cells or host cells on tumor growth, we established a tumorigenic cell line (MKER) from the kidney of a C57BL/6 mouse and performed syngeneic transplantation experiments. Our results indicate that when RECK expression is low in host cells, transplanted MKER cells grow faster and kill the animal more rapidly. Since RECK is required for the formation of proper fibrillin fibers that serve as a tissue reservoir for precursors of TGFβ-family cytokines, we assessed the levels of TGFβ1 in the peripheral blood. We found a significant increase in TGFβ1 in RECK-Hypo mice compared to wild-type mice. We also found that the proportion of FOXP3-positive regulatory T (Treg) cells among splenocytes was higher in RECK-Hypo mice compared to the control mice. Furthermore, the number of FOXP3-positive cells in spontaneous hematopoietic neoplasms in the lungs as well as tumors that formed after MKER transplantation was significantly higher in RECK-Hypo mice compared to the control mice. These findings indicate that RECK-mediated tumor suppression involves a non-cell-autonomous mechanism and that possible roles of TGFβ1 and Treg cells in such a mechanism warrant further study., (© 2024 The Author(s). Journal of Cellular Physiology published by Wiley Periodicals LLC.)

Teriparatide is a peptide derived from a parathyroid hormone (PTH) and an osteoporosis therapeutic drug with potent bone formation-promoting activity. To identify novel druggable genes that act downstream of PTH signaling and are potentially involved in bone formation, we screened PTH target genes in mouse osteoblast-like MC3T3-E1 cells. Here we show that Gprc5a, encoding an orphan G protein-coupled receptor, is a novel PTH-inducible gene and negatively regulates osteoblast proliferation and differentiation. PTH treatment induced Gprc5a expression in MC3T3-E1 cells, rat osteosarcoma ROS17/2.8 cells, and mouse femurs. Induction of Gprc5a expression by PTH occurred in the absence of protein synthesis and was mediated primarily via the cAMP pathway, suggesting that Gprc5a is a direct target of PTH signaling. Interestingly, Gprc5a expression was induced additively by co-treatment with PTH and 1α, 25-dihydroxyvitamin D3 (calcitriol), or retinoic acid in MC3T3-E1 cells. Reporter analysis of a 1 kb fragment of human GPRC5A promoter revealed that the promoter fragment showed responsiveness to PTH via the cAMP response element, suggesting that GPRC5A is also a PTH-inducible gene in humans. Gprc5a knockdown promoted cell viability and proliferation, as demonstrated by MTT and BrdU assays. Gprc5a knockdown also promoted osteoblast differentiation, as indicated by gene expression analysis and mineralization assay. Mechanistic studies showed that Gprc5a interacted with BMPR1A and suppressed BMP signaling induced by BMP-2 and constitutively active BMP receptors, ALK2 (ACVR1) Q207D and ALK3 (BMPR1A) Q233D. Thus, our results suggest that Gprc5a is a novel gene induced by PTH that acts in an inhibitory manner on both cell proliferation and osteoblast differentiation and is a candidate for drug targets for osteoporosis., (© 2024 Wiley Periodicals LLC.)

Background: Although robot-assisted radical prostatectomy (RARP) and intensity-modulated radiotherapy are the leading respective techniques of prostatectomy and radiotherapy for localized prostate cancer, almost no study has directly compared their outcomes; none have compared mortality outcomes., Methods: We compared 6‑year outcomes of RARP (n = 500) and volumetric modulated arc therapy (VMAT, a rotational intensity-modulated radiotherapy, n = 360) in patients with cT1-4N0M0 prostate cancer. We assessed oncological outcomes, namely overall survival (OS), cancer-specific survival (CSS), radiological recurrence-free survival (rRFS), and biochemical recurrence-free survival (bRFS), using propensity score matching (PSM). We also assessed treatment-related complication outcomes of prostatectomy and radiotherapy., Results: The median follow-up duration was 79 months (> 6 years). PSM generated a matched cohort of 260 patients (130 per treatment group). In the matched cohort, RARP and VMAT showed equivalent results for OS, CSS, and rRFS: both achieved excellent 6‑year outcomes for OS (> 96%), CSS (> 98%), and rRFS (> 91%). VMAT had significantly longer bRFS than RARP, albeit based on different definitions of biochemical recurrence. Regarding complication outcomes, patients who underwent RARP had minimal (2.6%) severe perioperative complications and achieved excellent continence recovery (91.6 and 68.8% of the patients achieved ≤ 1 pad/day and pad-free, respectively). Patients who underwent VMAT had an acceptable rate (20.0%) of grade ≥ 2 genitourinary complications and a very low rate (4.4%) of grade ≥ 2 gastrointestinal complications., Conclusion: On the basis of PSM after a 6-year follow-up, RARP and VMAT showed equivalent and excellent oncological outcomes, as well as acceptable complication profiles., (© 2024. The Author(s).)

Objective: It is presumed that people with nervous tendencies brush their teeth for long durations, and, we aimed to investigate how nervous tendencies affect oral health status and lifestyle habits., Subjects and Methods: Three hundred and sixty patients who visited the Senri Dental Clinic, affiliated with the Sunstar Foundation, and were being treated for periodontal diseases between 11 January 2017 and 10 April 2017 were enrolled. A total of 323 respondents (101 men and 222 women) were considered eligible. Nervous tendencies were investigated using the Fujinami neurotic index (FNI) and its derivative, the neurotic index (NI). Patients with NIs of ≥20 were included in the 'needs caution' group, whereas those with NIs of <19 comprised the 'healthy' group. The plaque score; periodontal pocket depth; bleeding on probing degree; gingival recession; crevice defects; oral conditions, such as cervical fillings and lifestyle habits were compared between the groups., Results and Discussion: No statistically significant differences in oral status were observed between the groups. On the other hand, the needs caution group had significantly longer brushing durations and lower usage of auxiliary teeth cleaning tools than the healthy group. Sleep duration was significantly shorter in the needs caution group than in the healthy group., Conclusions: Patients with strong nervous tendencies had long oral brushing durations and low usage of auxiliary cleaning tools. However, these factors did not negatively affect oral health status. These results could aid in understanding patients with strong nervous tendencies and in developing appropriate dental health guidance measures., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To investigate the precise mechanism of xenon (Xe), pharmacologically isolated AMPA/KA and NMDA receptor-mediated spontaneous (s) and evoked (e) excitatory postsynaptic currents (s/eEPSC AMPA/KA and s/eEPSC NMDA ) were recorded from mechanically isolated single spinal sacral dorsal commissural nucleus (SDCN) neurons attached with glutamatergic nerve endings (boutons) using conventional whole-cell patch-clamp technique. We analysed kinetic properties of both s/eEPSC AMPA/KA and s/eEPSC NMDA by focal single- and/or paired-pulse electrical stimulation to compare them. The s/eEPSC NMDA showed smaller amplitude, slower rise time, and slower 1/e decay time constant (τ Decay ) than those of s/eEPSC AMPA/KA . We previously examined how Xe modulates s/eEPSC AMPA/KA , therefore, examined the effects on s/eEPSC NMDA in the present study. Xe decreased the frequency and amplitude of sEPSC NMDA , and decreased the amplitude but increased the failure rate and paired-pulse ratio of eEPSC NMDA without affecting their τ Decay . It was concluded that Xe might suppress NMDA receptor-mediated synaptic transmission via both presynaptic and postsynaptic mechanisms., (Copyright © 2024. Published by Elsevier B.V.)

The intricate distribution of the facial nerve within the temporal bone is crucial in otological surgery. Anomalous facial nerve pathways are occasionally observed in middle ear malformations, although intra-tympanic bifurcation of the facial nerve is rare. When managing ossicular malformations with atypical facial nerve trajectories, hearing reconstruction should be prioritized based on the trajectory pattern and presence of the oval window. In this case, stapes surgery was performed due to facial nerve bifurcation within the tympanic cavity. In this case report, a 15-year-old female underwent stapes surgery due to gradually worsening conductive hearing loss. She was monitored at another hospital because of left-sided hearing loss at birth screening using automated auditory brainstem response. Her left ear initially had mild hearing loss, while her right ear remained within normal limits. However, her hearing deteriorated progressively, leading to significant daily challenges by age seven, prompting referral to our hospital. Intraoperatively, findings included defects in the incus-long process and stapes head, along with facial nerve bifurcation around the oval window, and the stapes footplate had poor flexibility. Stapedotomy was performed cautiously to preserve the facial nerve, utilizing a Teflon piston wire for sound transmission reconstruction. Postoperatively, the patient experienced no complications or facial nerve palsy, with hearing improving to 28.8 dB. Understanding the precise pathophysiology of middle ear anomalies is crucial for selecting appropriate surgical approaches. Even though the anomalies could not be evaluated prior to surgery, surgeons must carefully consider the risk of facial nerve injury and choose the optimal technique and reconstruction method tailored to each case, as predicting outcomes solely from preoperative evaluations can be challenging., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Miura et al.)

ADP-ribosylation factors (ARFs) are a family of small GTPases that regulate vesicle trafficking and actin dynamics in cells. Recent genetic analyses have revealed associations between variations in ARF genes and neurodevelopmental disorders, although their pathophysiological significance remains unclear. In this study, we conducted biochemical, cell biological, and in vivo analyses of ARF1 variants linked to neurodevelopmental disorders. The mant-GDP dissociation assay revealed that ARF1-p.R19C, -p.F51L, -p.R99C, and -p.R99H exhibit higher GDP/GTP exchange activity compared to ARF1 wild type (WT). The GTPase-activating protein (GAP) increased the GTPase activity of WT, p.R19C, p.Y35H, p.F51L, p.P131L, and p.P131R, but not of p.Y35D, p.T48I, p.R99C, and p.R99H. The transient expression of p.R99C, p.R99H, and p.K127E in mammalian cells resulted in the disruption of the Golgi apparatus. In utero electroporation-mediated gene transfer into the cortical neurons of embryonic mice demonstrated that p.R99C, p.R99H, and p.K127E cause a migration defect. Expression of these variants resulted in the expansion of the Golgi apparatus in migrating cortical neurons. These findings suggest that the ARF1 variants linked to neurodevelopmental disorders, specifically p.R99C, p.R99H, and p.K127E, disrupt the structure of the Golgi apparatus, thereby leading to a developmental defect of cortical neurons., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Area under the concentration-time curve (AUC)-guided dosing of vancomycin was introduced in a clinical setting; however, the target range of non-steady-state AUCs, such as Day 1 AUC and Day 2 AUC, remains controversial. Therefore, we sought to determine pharmacokinetic parameter thresholds and identify independent risk factors associated with acute kidney injury (AKI) to establish a safe initial dosing design for vancomycin administration., Methods: A single-centre, retrospective, cohort study of hospitalized patients treated with vancomycin was conducted to determine the threshold of both non-steady-state AUCs (Day 1 and 2 AUCs) and trough levels at the first blood sampling point (therapeutic drug monitoring, TDM). In addition, independent risk factors associated with AKI were evaluated using univariate and multivariate logistic regression analyses., Results: The thresholds for predicting AKI were estimated as 456.6 mg·h/L for AUC0-24h, 554.8 mg·h/L for AUC24-48h, 1080.8 mg·h/L for AUC0-48h and 14.0 μg/mL for measured trough levels, respectively. In a multivariate analysis, Day 2 AUC ≥ 554.8 mg·h/L [adjusted odds ratio (OR), 57.16; 95% confidence interval (CI), 11.95-504.05], piperacillin/tazobactam (adjusted OR, 15.84; 95% CI, 2.73-127.70) and diuretics (adjusted OR, 4.72; 95% CI, 1.13-21.01) were identified as risk factors for AKI., Conclusions: We identified thresholds for both AUCs in the non-steady-state and trough levels at the first TDM. Our results highlight the importance of monitoring not only the AUC but also trough levels during vancomycin treatment to reduce the likelihood of AKI., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Sleep deprivation (SD) triggers mitochondrial dysfunction and neural inflammation, leading to cognitive impairment and mental issues. However, the mechanism involving mitochondrial dysfunction and neural inflammation still remains unclear. Here, we report that SD rats exhibited multiple behavioral disorders, brain oxidative stress, and robust brain mitochondrial DNA (mtDNA) oxidation. In particular, SD activated microglia and microglial mtDNA efflux to the cytosol and provoked brain pro-inflammatory cytokines. We observed that the mtDNA efflux and pro-inflammatory cytokines significantly reduced with the suppression of the mtDNA oxidation. With the treatment of a novel mitochondrial nutrient, hydroxytyrosol butyrate (HTHB), the SD-induced behavioral disorders were significantly ameliorated while mtDNA oxidation, mtDNA release, and NF-κB activation were remarkably alleviated in both the rat brain and the N9 microglial cell line. Together, these results indicate that microglial mtDNA oxidation and the resultant release induced by SD mediate neural inflammation and HTHB prevents mtDNA oxidation and efflux, providing a potential treatment for SD-induced mental issues.

Adjuvants are effective tools to enhance vaccine efficacy and control the type of immune responses such as antibody and T helper 1 (Th1)- or Th2-type responses. Several studies suggest that interferon (IFN)-γ-producing Th1 cells play a significant role against infections caused by intracellular bacteria and viruses; however, only a few adjuvants can induce a strong Th1-type immune response. Recently, several studies have shown that lipid nanoparticles (LNPs) can be used as vaccine adjuvants and that each LNP has a different adjuvant activity. In this study, we screened LNPs to develop an adjuvant that can induce Th1 cells and antibodies using a conventional influenza split vaccine (SV) as an antigen in mice. We observed that LNP with 1,2-di-O-octadecenyl-3-trimethylammonium-propane (DOTMA) as a component lipid (DOTMA-LNP) elicited robust SV-specific IgG1 and IgG2 responses compared with SV alone in mice and was as efficient as SV adjuvanted with other adjuvants in mice. Furthermore, DOTMA-LNPs induced robust IFN-γ-producing Th1 cells without inflammatory responses compared to those of other adjuvants, which conferred strong cross-protection in mice. We also demonstrated the high versatility of DOTMA-LNP as a Th1 cell-inducing vaccine adjuvant using vaccine antigens derived from severe acute respiratory syndrome coronavirus 2 and Streptococcus pneumoniae . Our findings suggest the potential of DOTMA-LNP as a safe and effective Th1 cell-inducing adjuvant and show that LNP formulations are potentially potent adjuvants to enhance the effectiveness of other subunit vaccines.

Background: Anticipatory chemotherapy-induced nausea and vomiting (CINV) is a conditioned response influenced by the severity and duration of previous emetic responses to chemotherapy. We aimed to evaluate the efficacy of non-pharmacologic interventions for anticipatory CINV among patients with cancer., Methods: We conducted a systematic search in databases, including PubMed, the Cochrane Library, CINAHL, and Ichushi-Web, from January 1, 1990, to December 31, 2020. Randomized controlled trials, non-randomized designs, observational studies, or case-control studies that utilized non-pharmacological therapies were included. The primary outcomes were anticipatory CINV, with an additional investigation into adverse events and the costs of therapies. The risk-of-bias for each study was assessed using the Cochrane risk-of-bias tool, and meta-analysis was performed using Revman 5.4 software., Results: Of the 107 studies identified, six met the inclusion criteria. Three types of non-pharmacological treatments were identified: systematic desensitization (n = 2), hypnotherapy (n = 2), and yoga therapy (n = 2). Among them, systematic desensitization significantly improved anticipatory CINV as compared to that in the control group (nausea: risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.49-0.72, p < 0.00001; vomiting: RR = 0.54, 95% CI = 0.32-0.91, p = 0.02). However, heterogeneity in outcome measures precluded meta-analysis for hypnotherapy and yoga. Additionally, most selected studies had a high or unclear risk of bias, and adverse events were not consistently reported., Conclusions: Our findings suggest that systematic desensitization may effectively reduce anticipatory CINV. However, further research is warranted before implementation in clinical settings., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: To investigate the surgical outcomes and postoperative survival prognostic factors of intractable secondary spontaneous pneumothorax., Methods: A total of 95 patients who underwent thoracoscopic surgery for intractable secondary spontaneous pneumothorax between April 2010 and March 2020 were included in this study. These patients were classified into interstitial pneumonia and non-interstitial pneumonia groups, and a comparative study was performed on surgical outcomes and postoperative survival prognostic factors., Results: There was no difference in the 1-year overall survival rate between the two groups. However, the 3-year overall survival rate was significantly lower in the interstitial pneumonia group than in the non-interstitial pneumonia group. The differences in short-term surgical outcomes (persistent air leakage, postoperative complications, etc.) were not significant between the two groups. Univariate analysis revealed that the drainage period, the development of postoperative complications, and recurrence were significant independent postoperative survival prognostic factors for all cases. Postoperative complications were the only associated postoperative survival prognostic factor for interstitial pneumonia pneumothorax in the multivariate analysis., Conclusion: The development of postoperative complications can cause poor postoperative survival prognosis of intractable secondary spontaneous pneumothorax due to interstitial pneumonia., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis 2023 was extensively revised to reflect the latest advances in antineoplastic agents, antiemetics, and antineoplastic regimens. This update provides new evidence on the efficacy of antiemetic regimens., Methods: Guided by the Minds Clinical Practice Guideline Development Manual of 2017, a rigorous approach was used to update the guidelines; a thorough literature search was conducted from January 1, 1990, to December 31, 2020., Results: Comprehensive process resulted in the creation of 13 background questions (BQs), 12 clinical questions (CQs), and three future research questions (FQs). Moreover, the emetic risk classification was also updated., Conclusions: The primary goal of the present guidelines is to provide comprehensive information and facilitate informed decision-making, regarding antiemetic therapy, for both patients and healthcare providers., (© 2024. The Author(s).)

We report a rare case of spontaneous regression (SR) in an elderly untreated patient with multiple solitary plasmacytoma (MSP). Diagnosis of MSP was confirmed through surgical resection of the left nasal cavity mass and subsequent biopsy of the right humerus. The patient was considered ineligible for chemotherapy due to poor performance status. At 3-month post-diagnosis, the patient's condition worsened with deteriorating bone lesions and emergence of a new serum monoclonal protein. However, these clinical findings completely disappeared at 6 months, and positron emission tomography-computed tomography at 1 year confirmed complete metabolic remission. Notably, peripheral blood lymphocyte counts were inversely correlated with tumor progression and remission. Pathological re-evaluation of the initial biopsy specimens revealed programmed cell death protein 1 (PD-1) expression in tumor-infiltrating CD8 + T cells. In addition, tumor cells were infected with Epstein-Barr virus (EBV) but were negative for programmed cell death ligand 1 (PD-L1) expression, which is the most potent immune escape mechanism in tumor cells. While the mechanism underlying SR remains unclear, our findings suggest that host immune response as well as EBV infection may contribute to SR. Further studies are needed to elucidate the clinicopathologic mechanisms of tumor regression in plasma cell neoplasms., (© 2024. Japanese Society of Hematology.)

In recent years, randomized controlled trials have demonstrated that upfront androgen receptor signaling inhibitors (ARSIs) prolong overall survival (OS) compared with androgen deprivation therapy (ADT) alone or combined androgen blockade (CAB) in patients with metastatic castration-sensitive prostate cancer (mCSPC). However, it remains unclear whether upfront ARSI is superior to CAB in Asian populations, among which the efficacy of ADT/CAB is considered relatively high. In this study, we compared the oncological outcomes of upfront ARSI and CAB in Japanese patients with mCSPC. Patients with mCSPC who underwent systemic therapy between May 2009 and October 2023 were enrolled retrospectively. Propensity score matching (PSM) was performed to compare the castration-resistant prostate cancer-free survival (CRPC-FS), cancer-specific survival (CSS), and OS between patients treated with upfront ARSI (ARSI group) and those treated with CAB (CAB group). In total, 30 and 142 patients were enrolled in the ARSI and CAB groups, respectively. After PSM (25 patients in each group), CRPC-FS was significantly longer in the ARSI group than in the CAB group (median: 36.7 vs. 12.3 months, hazard ratio: 0.44, 95% confidence interval: 0.20-0.97, p = 0.035). No significant differences were observed in CSS or OS between the two groups. In conclusion, when compared to CAB, upfront ARSI might have the potential to extend CRPC-FS among individuals in the Japanese population., Competing Interests: The authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)

Background: Interoception encompasses the conscious awareness of homeostasis in the body. Given that fetal movement awareness is a component of interoception in pregnant women, the timing of initial detection of fetal movement may indicate individual differences in interoceptive sensitivity., Objective: The aim of this study is to determine whether the association between the gestational week of initial movement awareness and interoception can be a convenient evaluation index for interoception in pregnant women., Methods: A cross-sectional study was conducted among 32 pregnant women aged 20 years or older at 22-29 weeks of gestation with stable hemodynamics in the Obstetric Outpatient Department. Interoception was assessed using the heartbeat-counting task, with gestational weeks at the first awareness of fetal movement recorded via a questionnaire. Spearman rank correlation was used to compare the gestational weeks at the first awareness of fetal movement and heartbeat-counting task scores., Results: A significant negative correlation was found between the gestational weeks at the first fetal movement awareness and heartbeat-counting task performance among all participants (r=-0.43, P=.01) and among primiparous women (r=-0.53, P=.03) but not among multiparous women., Conclusions: Individual differences in interoception appear to correlate with the differences observed in the timing of the first awareness of fetal movement., (©Miku Furusho, Minami Noda, Yoko Sato, Yoshiko Suetsugu, Seiichi Morokuma. Originally published in the Asian/Pacific Island Nursing Journal (https://apinj.jmir.org), 26.06.2024.)

Background: The innovative peak frequency mapping facilitates the quantification of electrogram sharpness. However, reference values for normal atrial tissue are currently undefined. In this study, we explored the distribution of peak frequency and omnipolar peak-to-peak voltage (V-max) in a normal heart., Methods: Twenty-two patients with structurally normal heart were included. Either the right atrium (RA) and superior vena cava (SVC) or the left atrium (LA) and pulmonary veins (PVs) were mapped during sinus rhythm., Results: In total, 13,654 points in the RA and 4143 points in the SVC from 15 patients and 4662 points in the LA and 2761 points in PVs from 7 patients were analyzed. The correlation between peak frequency and V-max was weak (R = 0.223). The median peak frequency was larger in the SVC than in the RA (441 [358-524] Hz vs. 358 [291-441] Hz, P < 0.0001) and in PVs than in the LA (346 [253-441] Hz vs. 323 [262-397] Hz, P < 0.0001). Conversely, the median V-max was smaller in the SVC than in the RA (1.96 [0.77-3.75] mV vs. 4.11 [2.10-6.83] mV, P < 0.0001) and in PVs than in the LA (1.16 [0.33-3.17] mV vs. 4.42 [2.63-6.84] mV, P < 0.0001). More than 95% of peak frequencies were > 174 Hz in the RA and > 185 Hz in the LA, and > 95% of V-maxes were > 0.52 and > 1.07 mV in the RA and LA, respectively., Conclusion: Given the limited correlation between peak frequency and V-max, and recognizing their potential to provide distinct information, they can be used complementarily. Employing these parameters to extract varied insights can provide comprehensive understandings of tissue characteristics., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Although uterine perforation is a rare but serious complication, intrauterine devices are globally popular and effective contraceptive methods., Case Presentation: A 76-year-old female patient manifesting symptoms of vaginal leakage and lower abdominal discomfort was admitted to our hospital. Diagnostic imaging identified a vesicovaginal fistula and bladder calculi attributable to perforation of the bladder by an intrauterine device that had been inserted over four decades ago. The patient underwent open surgery for cystolith removal and vesicovaginal fistula repair., Conclusions: If a patient with an intrauterine device complains of bladder stones or ongoing lower urinary tract symptoms, bladder perforation caused by the device should be considered in the differential diagnosis., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Objective: Pediatric obstructive sleep apnea (OSA) caused by adenoids or an enlarged palatine tonsil has a negative impact on physical and mental growth. Surgical removal of the tissue is effective but entails a life-threatening risk of postoperative bleeding, which is up to 30 times higher in chronic pediatric disease cases. However, endoscopes and resection devices provide safe, reliable surgical methods. Here, we report the efficacy and safety of endoscopic powered intracapsular tonsillectomy and adenoidectomy (PITA) for pediatric OSA in patients with high-risk comorbidities., Methods: This retrospective case series included pediatric patients with OSA who underwent PITA at a single tertiary medical center between April 2017 and May 2023. Ten patients (three males and seven females; mean age 6.4 years, range 2-12 years) were included; all met the Japanese criteria for complex chronic pediatric conditions., Results: The average operative time was 61 min; a microdebrider was used in eight cases and a coblator in two cases. Although there was no postoperative bleeding, one case experienced regrowth., Conclusions: Our data show that an endoscopic PITA approach could reduce the risk of severe bleeding and relieve the sleeping conditions of pediatric patients with complex chronic OSA., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Noda et al.)

Bacteria produce and release small signal molecules, autoinducers, as an indicator of their cell density. The system, called a quorum-sensing (QS) system, is used to control not only virulence factors but also antibiotic production, sporulation, competence, and biofilm formation in bacteria. Different from antibiotics, QS inhibitors are expected to specifically repress the virulence factors in pathogenic bacteria without inhibiting growth or bactericidal effects. Therefore, since QS inhibitors have little risk of antibiotic-resistant bacteria emergence, they have been proposed as promising anti-bacterial agents. In the present study, we aimed to find new QS inhibitors that prohibit the signaling cascade of autoinducer 3 (AI-3) recognized by a QseCB two-component system that regulates some virulence factors of pathogens, such as enterohemorrhagic Escherichia coli (EHEC) and Salmonella enterica subsp. enterica serovar Typhimurium. We have established the method for QS-inhibitor screening using a newly constructed plasmid pLES-AQSA. E. coli DH5α transformed with the pLES-AQSA can produce β-galactosidase that converts 5-bromo-4-chloro-3-indolyl β-d-galactopyranoside (X-gal) into blue pigment (5-bromo-4-chloro-indoxyl) under the control of the QseCB system. By screening, Heyndrickxia coagulans (formerly Bacillus coagulans) 29-2E was found to produce an exopolysaccharide (EPS)-like water-soluble polymer that prohibits QseCB-mediated β-galactosidase production without antibacterial activities. Further, the simultaneous injection of the 29-2E strain significantly improves the survival rate of Salmonella Typhimurium-infected silkworm larvae (from 0% to 83.3%), suggesting that the substance may be a promising inhibitor against the virulence of pathogens without risk of the emergence of antibiotic-resistant bacteria., (Copyright © 2024 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Objective: This study aims to compare the post-transplant survival of untwinned single lung transplantation (SLT) to twinned SLT. In untwinned SLT, the contralateral lung is judged unsuitable for transplantation and might affect the lung graft within the donor body and recipient survival after SLT., Methods: A retrospective analysis was conducted on 84 SLT recipients at our center, divided into untwinned SLT and twinned SLT groups. The demographics of donors and recipients, surgical characteristics, complications, mortality, and survival rates were compared., Results: There were no significant differences in recipient and donor demographics between the two groups. Surgical characteristics showed no significant differences. Microbiological findings of the transplanted lungs indicated a low incidence of positive cultures in both groups. 3-month to 1-year mortality and overall survival rates were comparable between the two groups., Conclusion: At our institution, both untwinned and twinned SLT procedures exhibited excellent survival rates without significant differences between the two procedures. The favorable outcomes observed may be associated with the strategic advantages of Japan's MC system and the diligent management of marginal donor lungs although this requires further investigation to elucidate the specific contributory factors., (© 2023. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

A 41-year-old woman with lymphangioleiomyomatosis developed a bronchial anastomotic stenosis after left single lung transplantation (LTx). A part of the hyperinflated right native lung was excised in an attempt to remedy the left lung compression, which appeared to affect the bronchial anastomotic stenosis and ventilation/perfusion mismatch. However, a persistent air leak after the surgery caused empyema and an open window thoracotomy (OWT) was performed. She remained oxygen-dependent and was relisted for lung transplantation. A right single LTx on the side of OWT was performed, achieving long-term survival with no activity limitations for the patient. We report here the first successful LTx after OWT for empyema., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Plant-derived lactic acid bacteria are major fermentation organisms that can grow in medicinal herb extracts enriched with phytochemicals like glycosides, phenolic acids, flavonoids, and tannins. Fermentation with strain-specific Lactobacilli harboring metabolic enzymes can increase the bioactivity and bioavailability of medicinal herbs. Fermentation of extracts of Artemisia princeps and Paeonia lactiflora has been previously found to increase their bioactivities. Therefore, this study explores the possibility of increasing the bioactivity of Mentha arvensis (Mentha) extract against lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells by fermenting with plant-derived probiotic strains Lactobacillus (Lact.) plantarum SN13T and Pediococcus (Ped.) pentosaceus LP28. As a result, fermentation with SN13T significantly increased the bioactivity of Mentha extract as compared to unfermented or LP28-fermented extracts. This higher bioactivity was associated with the metabolism of rosmarinic acid (RA) and caffeic acid (CA), the major bioactive phenolic acids reported in Mentha, along with the production of the metabolite dihydrocaffeic acid (DHCA). DHCA was found to be a more potent LPS-induced nitric oxide (NO) inhibitor than its precursor phenolic acids. The metabolism of RA to DHCA via CA could be mediated by the enzymes cinnamoyl ester hydrolase and hydroxycinnamate reductases, encoded by the ceh gene and the hcrRABC gene operon, respectively, which were identified in the complete genome sequence of Lact. plantarum SN13T but were absent in Ped. pentosaceus LP28. The genes hcrA, hcrB, and hcrC were significantly and time-dependently overexpressed in Lact. plantarum SN13T when grown in the Mentha extract, suggesting the role of phenolic acid metabolism in enhancing its bioactivity., (© 2023. The Author(s).)

This study investigated the wettability and consistency of various endodontic sealers, both inorganic and organic, and evaluated their sealing ability of root canals using the single-cone obturation technique, with and without ethylenediaminetetraacetic acid (EDTA) treatment. Bovine root canals were endodontically prepared and filled in preparation for the dye penetration test with toluidine blue solution. All sealers exhibited contact angles similar to or lower than dentin and displayed superior consistency. Among the sealers, organic sealers used without EDTA treatment showed reduced dye penetration compared to inorganic sealers. However, some inorganic and organic sealers showed dye penetration in the sealer and dentin of root canals subjected to EDTA treatment. In conclusion, the single-cone obturation technique, combined with these endodontic sealers, achieved close contact with root canal dentin due to their wettability and consistency. However, the sealing ability of certain sealers was influenced by EDTA treatment.

Background: The integration of artificial intelligence (AI), particularly deep learning models, has transformed the landscape of medical technology, especially in the field of diagnosis using imaging and physiological data. In otolaryngology, AI has shown promise in image classification for middle ear diseases. However, existing models often lack patient-specific data and clinical context, limiting their universal applicability. The emergence of GPT-4 Vision (GPT-4V) has enabled a multimodal diagnostic approach, integrating language processing with image analysis., Objective: In this study, we investigated the effectiveness of GPT-4V in diagnosing middle ear diseases by integrating patient-specific data with otoscopic images of the tympanic membrane., Methods: The design of this study was divided into two phases: (1) establishing a model with appropriate prompts and (2) validating the ability of the optimal prompt model to classify images. In total, 305 otoscopic images of 4 middle ear diseases (acute otitis media, middle ear cholesteatoma, chronic otitis media, and otitis media with effusion) were obtained from patients who visited Shinshu University or Jichi Medical University between April 2010 and December 2023. The optimized GPT-4V settings were established using prompts and patients' data, and the model created with the optimal prompt was used to verify the diagnostic accuracy of GPT-4V on 190 images. To compare the diagnostic accuracy of GPT-4V with that of physicians, 30 clinicians completed a web-based questionnaire consisting of 190 images., Results: The multimodal AI approach achieved an accuracy of 82.1%, which is superior to that of certified pediatricians at 70.6%, but trailing behind that of otolaryngologists at more than 95%. The model's disease-specific accuracy rates were 89.2% for acute otitis media, 76.5% for chronic otitis media, 79.3% for middle ear cholesteatoma, and 85.7% for otitis media with effusion, which highlights the need for disease-specific optimization. Comparisons with physicians revealed promising results, suggesting the potential of GPT-4V to augment clinical decision-making., Conclusions: Despite its advantages, challenges such as data privacy and ethical considerations must be addressed. Overall, this study underscores the potential of multimodal AI for enhancing diagnostic accuracy and improving patient care in otolaryngology. Further research is warranted to optimize and validate this approach in diverse clinical settings., (©Masao Noda, Hidekane Yoshimura, Takuya Okubo, Ryota Koshu, Yuki Uchiyama, Akihiro Nomura, Makoto Ito, Yutaka Takumi. Originally published in JMIR AI (https://ai.jmir.org), 31.05.2024.)

Recent advancements in computed tomography (CT) scanning have improved the detection rates of peripheral pulmonary nodules, including those with ground-glass opacities (GGOs). This study focuses on part-solid pure ground-glass nodules (GGNs) and aims to identify imaging predictors that can reliably differentiate primary lung cancer from nodules with other diagnoses among part-solid GGNs on high-resolution CT (HRCT). A retrospective study was conducted on 609 patients who underwent surgical treatment or observation for lung nodules. Radiological findings from pre-operative HRCT scans were reviewed and several CT imaging features of part-solid GGNs were examined for their positive predictive value to identify primary lung cancer. The proportions of the nodules with a final diagnosis of primary lung cancer were significantly higher in part-solid GGNs (91.9%) compared with solid nodules (70.3%) or pure GGNs (66.7%). Among CT imaging features of part-solid GGNs that were evaluated, consolidation-to-tumor ratio (CTR) < 0.5 (98.1%), pleural indentation (96.4%), and clear tumor border (96.7%) had high positive predictive value to identify primary lung cancer. When two imaging features were combined, the combination of CTR < 0.5 and a clear tumor border was identified to have 100% positive predictive values with a sensitivity of 40.8%. Thus we conclude that part-solid GGNs with a CTR < 0.5 accompanied by a clear tumor border evaluated by HRCT are very likely to be primary lung cancers with an acceptable sensitivity. Preoperative diagnostic procedures to obtain a pathological diagnosis may potentially be omitted in patients harboring such part-solid GGNs.

Non-islet cell tumor hypoglycemia (NICTH) is one of the paraneoplastic syndromes manifesting severe hypoglycemia caused by aberrant production of high-molecular-weight insulin-like growth factor 2 (big-IGF2). Two surgical cases of extremely large thoracic solitary fibrous tumors (SFT) with unusual history of NICTH are presented. One case manifested severe hypoglycemia after four years of the first complete surgical resection of the tumor with potential malignant transformation, and the other case showed severe hypoglycemia after ten years of the first detection of the tumor. Meticulous laboratory testing, including serum endocrinological tests and western immunoblotting before and after surgery was performed, and both cases were diagnosed as NICTH. Both patients underwent open thoracic surgery. The patients showed normal glucose and hormone levels immediately after the resection of responsible tumors with elevated blood insulin concentration. SFTs are generally considered benign; however, life-threatening hypoglycemia can happen regardless of treatment. Careful follow-up of the tumor growth is warranted.

Purpose: Nutritional scores have been reported to be useful prognostic factors for various cancers. This study evaluated the usefulness of the preoperative controlling nutritional status (CONUT) score as a predictor of recurrence of non-small cell lung cancer (NSCLC)., Methods: The present study included 422 patients with stage I-IIIA NSCLC who underwent complete resection at Tohoku University Hospital between January 2010 and December 2016. The patients were divided into the low-CONUT and high-CONUT groups based on their CONUT scores. Overall survival (OS), recurrence-free survival (RFS), and cumulative recurrence rates in the low- and high-CONUT groups were evaluated retrospectively., Results: One hundred forty-seven patients (34.8%) were assigned to the high-CONUT group. The high-CONUT group had a significantly worse performance status, pleural invasion, vascular invasion, and lung metastasis. In the whole cohort, the low-CONUT group showed better overall survival, recurrence-free survival, and a low cumulative recurrence rate in comparison to the high-CONUT group. There was no significant difference in prognosis or recurrence between the low- and high-CONUT groups after propensity score matching., Conclusion: Patients with a high CONUT score may be at high risk of recurrence because of the high frequency of pleural invasion, vascular invasion, and lung metastasis., (© 2024. The Author(s).)

A biomembrane-related fibrillogenesis of Amyloid β from Alzheimer' disease (Aβ) is closely related to its accumulation behavior. A binding property of Aβ peptides from Alzheimer' disease to lipid membranes was then classified by a quartz crystal microbalance (QCM) method combined with an immobilization technique using thiol self-assembled membrane. The accumulated amounts of Aβ, Δf max , was determined from the measurement of the maximal frequency reduction using QCM. The plots of Δf max to Aβ concentration gave the slope and saturated value of Δf max , (Δf max ) sat that are the parameters for binding property of Aβ to lipid membranes. Therefore, the Aβ-binding property on lipid membranes was classified by the slope and (Δf max ) sat . The plural lipid system was described as X + Y where X = L 1 , L 1 /L 2 , and L 1 /L 2 /L 3 . The slope and (Δf max ) sat values plotted as a function of mixing ratio of Y to X was classified on a basis of the lever principle (LP). The LP violation observed in both parameters resulted from the formation of the crevice or pothole, as Aβ-specific binding site, generated at the boundary between l d and l o phases. The LP violation observed only in the slope resulted from glycolipid-rich domain acting as Aβ-specific binding site. Furthermore, lipid planar membranes indicating strong LP violation favored strong fibrillogenesis. Especially, lipid planar membranes indicating the LP violation only in the slope induced lateral aggregated and spherulitic fibrillar aggregates. Thus, the classification of Aβ binding property on lipid membranes appeared to be related to the fibrillogenesis with a certain morphology., 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. Toshinori Shimanouchi and Minoru Noda report financial support was provided by JSPS KAKENHI., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Genetic epidemiological evidence for the kidney function traits in East Asian population including Japanese remain still relatively unclarified. Especially, the number of GWASs for kidney traits reported still remains limited, and the sample size of each independent study is relatively small. Given the genetic variability between ancestries/ethnicities, implementation of GWAS with sufficiently large sample sizes in specific population of Japanese is considered meaningful., Methods: We conducted the GWAS meta-analyses of kidney traits by leveraging the GWAS summary data of the representative large genome cohort studies with about 200,000 Japanese participants (n = 202,406 for estimated glomerular filtration rate [eGFR] and n = 200,845 for serum creatinine [SCr])., Results: In the present GWAS meta-analysis, we identified 110 loci with 169 variants significantly associated with eGFR (on chromosomes 1-13 and 15-22; p < 5×10 -8 ), whereas we also identified 112 loci with 176 variants significantly associated with SCr (on chromosomes 1-22; p < 5×10 -8 ), of which one locus (more than 1Mb distant from known loci) with one variant (CD36 rs146148222 on chromosome 7) for SCr was considered as the truly novel finding., Conclusions: The present GWAS meta-analysis of largest genome cohort studies in Japanese provided some original genomic loci associated with kidney function in Japanese, which may contribute to the possible development of personalized prevention of kidney diseases based on genomic information in the near future.

Objective: This study aimed to reveal the association between pretreatment serum testosterone levels and prognosis in patients with metastatic hormone-sensitive prostate cancer treated with androgen deprivation therapy., Methods: A total of 91 patients were included in this retrospective study. Clinical data were obtained through chart review. Multivariate cox proportional hazards analyses addressed the impact of variables on castration-resistant prostate cancer-free and overall survivals., Results: During a median follow-up of 41.7 months, 61 (67%) and 49 (54%) patients developed castration-resistant prostate cancer and died, respectively. The median castration-resistant prostate cancer-free and overall survivals were 15.5 and 59.9 months, respectively. The cutoff value for discriminating between low- and high-testosterone levels was determined as 450 ng/dl by calculating the receiver operating characteristic curve. Patients in the low-testosterone group (n = 37) had a significantly higher body mass index, worse comorbidities represented by the higher Charlson comorbidity index and higher serum lactate dehydrogenase levels, than those in the high-testosterone group (n = 54). Castration-resistant prostate cancer free and overall survivals were significantly shorter in the low-testosterone group than in the high-testosterone group (P = 0.021 and P < 0.001, respectively). Multivariate analysis identified testosterone level of <450 ng/dl as an independent factor predicting development of castration-resistant prostate cancer (hazard ratio 2.28, P = 0.007), along with high-volume disease and Gleason score 9-10. Similarly, testosterone level of <450 ng/dl was independently associated with shorter overall survival (hazard ratio 2.84, P = 0.006), along with higher Charlson comorbidity index, visceral metastasis and higher alkaline phosphatase level., Conclusions: Lower baseline serum testosterone levels predict poor prognosis in patients with metastatic hormone-sensitive prostate cancer., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This study aimed to develop models to predict the 5-year incidence of type 2 diabetes mellitus (T2DM) in a Japanese population and validate them externally in an independent Japanese population., Methods: Data from 10,986 participants (aged 46-75 years) in the development cohort of the Japan Public Health Center-based Prospective Diabetes Study and 11,345 participants (aged 46-75 years) in the validation cohort of the Japan Epidemiology Collaboration on Occupational Health Study were used to develop and validate the risk scores in logistic regression models., Results: We considered non-invasive (sex, body mass index, family history of diabetes mellitus, and diastolic blood pressure) and invasive (glycated hemoglobin [HbA1c] and fasting plasma glucose [FPG]) predictors to predict the 5-year probability of incident diabetes. The area under the receiver operating characteristic curve was 0.643 for the non-invasive risk model, 0.786 for the invasive risk model with HbA1c but not FPG, and 0.845 for the invasive risk model with HbA1c and FPG. The optimism for the performance of all models was small by internal validation. In the internal-external cross-validation, these models tended to show similar discriminative ability across different areas. The discriminative ability of each model was confirmed using external validation datasets. The invasive risk model with only HbA1c was well-calibrated in the validation cohort., Conclusion: Our invasive risk models are expected to discriminate between high- and low-risk individuals with T2DM in a Japanese population.

Whole lung engineering and the transplantation of its products is an ambitious goal and ultimately a viable solution for alleviating the donor-shortage crisis for lung transplants. There are several limitations currently impeding progress in the field with a major obstacle being efficient revascularization of decellularized scaffolds, which requires an extremely large number of cells when using larger pre-clinical animal models. Here, we developed a simple but effective experimental pulmonary bioengineering platform by utilizing the lung as a scaffold. Revascularization of pulmonary vasculature using human umbilical cord vein endothelial cells was feasible using a novel in-house developed perfusion-based bioreactor. The endothelial lumens formed in the peripheral alveolar area were confirmed using a transmission electron microscope. The quality of engineered lung vasculature was evaluated using box-counting analysis of histological images. The engineered mouse lungs were successfully transplanted into the orthotopic thoracic cavity. The engineered vasculature in the lung scaffold showed blood perfusion after transplantation without significant hemorrhage. The mouse-based lung bioengineering system can be utilized as an efficient ex-vivo screening platform for lung tissue engineering., (© 2024. The Author(s).)

Facial nerve injuries stem from trauma or tumor surgery, triggering neurodegeneration and neuronal cell death in the facial nucleus, consequently inducing irreversible nerve paralysis. Following facial nerve transection, glial cells are activated and undergo proliferation, facilitating motor neuron survival, repair, and regeneration. Clinical approaches, including nerve anastomosis and hypoglossal nerve grafting, require delicate microscopic techniques. Recent advancements involve nerve reconstruction using polyglycolic acid (PGA) tubes, which yield nerve function improvement. However, the central pathophysiological effects of these procedures remain unclear. Therefore, using PGA tubes, we evaluated neurodegeneration and microglial inflammatory response in rats after facial nerve transection. Facial nerve functions were evaluated using vibrissae and blink reflex scores. In the end-to-end anastomosis and PGA tube reconstruction groups, a partial improvement in facial motor function was observed, with increased nerve fiber survival in the former. Approximately 90% of neurons survived in both groups, wherein gliosis exhibited increased microglial activation compared to that in the transection group. These results indicate that PGA tube-assisted nerve reconstruction post-facial nerve transection, although inferior to end-to-end anastomosis, improved certain functions and prevented neuronal cell death. Furthermore, the prolonged inflammatory response in the facial nerve nucleus underscored the correlation between neuronal function and survival and microglia., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Noda et al.)

Background: Artificial intelligence models can learn from medical literature and clinical cases and generate answers that rival human experts. However, challenges remain in the analysis of complex data containing images and diagrams., Objective: This study aims to assess the answering capabilities and accuracy of ChatGPT-4 Vision (GPT-4V) for a set of 100 questions, including image-based questions, from the 2023 otolaryngology board certification examination., Methods: Answers to 100 questions from the 2023 otolaryngology board certification examination, including image-based questions, were generated using GPT-4V. The accuracy rate was evaluated using different prompts, and the presence of images, clinical area of the questions, and variations in the answer content were examined., Results: The accuracy rate for text-only input was, on average, 24.7% but improved to 47.3% with the addition of English translation and prompts (P<.001). The average nonresponse rate for text-only input was 46.3%; this decreased to 2.7% with the addition of English translation and prompts (P<.001). The accuracy rate was lower for image-based questions than for text-only questions across all types of input, with a relatively high nonresponse rate. General questions and questions from the fields of head and neck allergies and nasal allergies had relatively high accuracy rates, which increased with the addition of translation and prompts. In terms of content, questions related to anatomy had the highest accuracy rate. For all content types, the addition of translation and prompts increased the accuracy rate. As for the performance based on image-based questions, the average of correct answer rate with text-only input was 30.4%, and that with text-plus-image input was 41.3% (P=.02)., Conclusions: Examination of artificial intelligence's answering capabilities for the otolaryngology board certification examination improves our understanding of its potential and limitations in this field. Although the improvement was noted with the addition of translation and prompts, the accuracy rate for image-based questions was lower than that for text-based questions, suggesting room for improvement in GPT-4V at this stage. Furthermore, text-plus-image input answers a higher rate in image-based questions. Our findings imply the usefulness and potential of GPT-4V in medicine; however, future consideration of safe use methods is needed., (©Masao Noda, Takayoshi Ueno, Ryota Koshu, Yuji Takaso, Mari Dias Shimada, Chizu Saito, Hisashi Sugimoto, Hiroaki Fushiki, Makoto Ito, Akihiro Nomura, Tomokazu Yoshizaki. Originally published in JMIR Medical Education (https://mededu.jmir.org), 28.03.2024.)

Objective: This study aimed to identify the amount of weight loss needed in patients with obesity to improve metabolic syndrome (MetS), a risk factor for cardiovascular disease (CVD), over a long period of time., Methods: A total of 576 patients with obesity were enrolled in this study. Effects of continuous physician-supervised weight loss on the cumulative MetS components excluding abdominal circumference (defined as obesity-related CVD risk score) were investigated during a 5-year follow-up period. The extent of weight loss required to reduce the obesity-related CVD risk components was assessed using receiver operating characteristic (ROC) curve analyses., Results: Of the 576 participants, 266 completed 5-year follow-up, with 39.1% and 24.1% of them achieving ≥5.0% and ≥7.5% weight loss at the 5-year follow-up, respectively. The area under the ROC curve for reducing the obesity-related CVD risk components was 0.719 [0.662-0.777] at 1 year and 0.694 [0.613-0.775] at 5 years. The optimal cut-off value for weight loss was 5.0% (0.66 sensitivity and 0.69 specificity) and the value with 0.80 specificity was 7.5% (0.45 sensitivity) at 5 years. Greater reductions in weight were associated with greater improvements in the obesity-related CVD risk score at all follow-up periods ( P -trend <0.001). Obesity-related CVD risk score was significantly improved by 5.0-7.5% and ≥7.5% weight loss at 1 year ( P = 0.029 and P < 0.001, respectively) and ≥7.5% weight loss at 5 years ( P = 0.034)., Conclusions: A weight loss of ≥5.0% at 1 year and ≥7.5% at 5 years could reduce the number of obesity-related CVD risk components in patients with obesity., 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 MT is an Editorial Board Member of this journal but was not involved in the peer-review process nor had access to any information regarding its peer-review., (Copyright © 2024 Yamakage, Jo, Tanaka, Kato, Hasegawa, Masuda, Matsuhisa, Kotani, Noda and Satoh-Asahara.)

Background: γ1-Adaptin is a subunit of adaptor protein complex-1 (AP-1), which regulates intracellular transport between the trans-Golgi network (TGN) and endosomes. Since expression levels of AP-1 subunits have been reported to be associated with cell proliferation and cancer malignancy, we investigated the relationships between the immunohistochemical expression of γ1-adaptin and both clinicopathological factors and relapse-free survival (RFS) in breast cancer tissue., Materials and Methods: SK-BR-3 cell line depleted of γ1-adaptin was used for cell proliferation, migration, and invasion assay. Intracellular localization of γ1-adaptin was examined with immunohistochemistry (IHC) using an antibody against γ1-adaptin, and with double immunohistofluorescence (IHF) microscopy using markers for the TGN and endosome. γ1-Adaptin intensities in IHC samples from 199 primary breast cancer patients were quantified and assessed in relation to clinicopathological factors and RFS., Results: Cell growth, migration, and invasion of SK-BR-3 cells were significantly suppressed by the depletion of γ1-adaptin. Although the staining patterns in the cancer tissues varied among cases by IHC, double IHF demonstrated that γ1-adaptin was mainly localized in EEA1-positive endosomes, but not in the TGN. γ1-Adaptin intensity was significantly higher in the tumor regions than in non-tumor regions. It was also higher in patients with Ki-67 (high), ER (-), PgR (-), and HER2 (+). Among subtypes of breast cancer, γ1-adaptin intensity was higher in HER2 than in luminal A or luminal B. The results of the survival analysis indicated that high γ1-adaptin intensity was significantly associated with worse RFS, and this association was also observed in group with ER (+), PgR (+), HER2 (-), Ki-67 (high), or luminal B. In addition, the Cox proportional hazards model showed that high γ1-adaptin intensity was an independent prognostic factor., Conclusion: These results suggest that the endosomal expression of γ1-adaptin is positively correlated with breast cancer malignancy and could be a novel prognostic marker., (© 2024. The Author(s).)