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The evidence of topological origin for the recently observed anomalous Hall effect remains elusive. Here, the authors report that the resonance of the optical Hall conductivity resulted from topological electronic structure gives rise to the large intrinsic anomalous Hall effect in the magnetic Weyl semimetal Co3Sn2S2.

The isotopic distribution of nuclei produced in the 50Ti + 249Cf reaction has been studied at the gas-filled recoil separator TASCA at GSI Darmstadt, which separates ions according to differences in magnetic rigidity. The bombardment was performed at an energy around the Bass barrier and with the TASCA magnetic fields set for collecting fusion-evaporation reaction products. Fifty-three isotopes located “north-east” of 208Pb were identified as recoiling products formed in non-fusion channels of the reaction. These recoils were implanted with energies in two distinct ranges; besides one with higher energy, a significant low-energy contribution was identified. The latter observation was not expected to occur according to kinematics of the known types of reactions, namely quasi-elastic, multi-nucleon transfer, deep-inelastic collisions or quasifission. The present observations are discussed within the framework of two-body kinematics passing through the formation of a composite system. Keywords: Production of radioactive nuclei, α decay, Multi-nucleon transfer reactions, Quasifission

Hypernuclear production cross sections have been deduced for the first time with induced reaction of heavy ion beam on fixed target and by means of the invariant mass method by the HypHI Collaboration exploiting the reaction of 6Li + 12C at 2A GeV or sNN=2.70 GeV. A production cross section of 3.9±1.4 μb for 3ΛH and of 3.1±1.0 μb for 4ΛH respectively in the projectile rapidity region was inferred as well as the total production cross section of the Λ hyperon was measured and found to be equal to 1.7±0.8 mb. A global fit based on a Bayesian approach was performed in order to include and propagate statistical and systematic uncertainties. Production ratios of 3ΛH/4ΛH, 3ΛH/Λ and 4ΛH/Λ were included in the inference procedure. The strangeness population factors S3 and S4 of 3ΛH and 4ΛH respectively were extracted. In addition, the multiplicities of the Λ hyperon, 3ΛH, and 4ΛH together with the rapidity and transversal momentum density distributions of the observed hypernuclei were extracted and reported.

The modification of Pt surfaces with organic compounds like melamine enhances oxygen reduction reaction activity and catalyst durability. Through first-principles free energy calculations utilizing thermodynamic integration and finite-temperature molecular dynamics, enhanced by machine learning force fields for efficient sampling of nanosecond-scale interfacial water fluctuations and incorporating corrections to accurately reproduce first-principles free energies, we demonstrate that melamine destabilizes OH adsorbates, facilitating their removal and enhancing catalytic activity. Unlike alloys, where OH destabilization is driven by changes in electronic structure and surface strain, melamine disrupts hydrogen bonding between OH and interfacial water. Structural and vibrational analyses reveal that melamine alters the water solvation structure, which is evident in modified radial distribution functions and a blue shift in the O-H stretching vibrations. These findings indicate that manipulating interfacial solvation with organic compounds could be a promising approach to enhance catalytic activity without compromising durability.

Insulin receptor substrate (IRS)-1 and IRS-2 are major molecules that transduce signals from insulin and insulin-like growth factor-I receptors. The physiological functions of these proteins have been intensively investigated in mice, while little is known in other animals. Our previous study showed that the disruption of IRS-2 impairs body growth but not glucose tolerance or insulin sensitivity in rats, which led us to hypothesize that IRS-1 plays more pivotal roles in insulin functions than IRS-2. Here, we created IRS-1 knockout (KO) rats to elucidate the physiological roles of IRS-1 in rats. The body weight of IRS-1 KO rats at birth was lower than that of wild-type (WT) littermates, and postnatal growth of IRS-1 KO rats was severely impaired. Compared with WT rats, IRS-1 KO rats displayed insulin resistance but maintained euglycemia because of compensatory hyperinsulinemia. In addition, despite the increased activity of insulin-stimulated IRS-2-associated phosphatidylinositol-3 kinase (PI3K), insulin-induced phosphorylation of the kinases downstream of PI3K was suppressed in the liver and skeletal muscle of IRS-1 KO rats. Taken together, these results indicate that in rats, IRS-1 is essential for normal growth and the glucose-lowering effects of insulin. IRS-1 appears to be more important than IRS-2 for insulin functions in rats., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

There are hundreds of rare syndromic diseases involving hearing loss, many of which are not targeted for clinical genetic testing. We systematically explored the genetic causes of undiagnosed syndromic hearing loss using a combination of whole exome sequencing (WES) and a phenotype similarity search system called PubCaseFinder. Fifty-five families with syndromic hearing loss of unknown cause were analyzed using WES after prescreening of several deafness genes depending on patient clinical features. Causative genes were identified in 22 families, including both established genes associated with syndromic hearing loss (PTPN11, CHD7, KARS1, OPA1, DLX5, MITF, SOX10, MYO7A, and USH2A) and those associated with nonsyndromic hearing loss (STRC, EYA4, and KCNQ4). Association of a DLX5 variant with incomplete partition type I (IP-I) anomaly of the inner ear was identified in a patient with cleft lip and palate and acetabular dysplasia. The study identified COL1A1, CFAP52, and NSD1 as causative genes through phenotype similarity search or by analogy. ZBTB10 was proposed as a novel candidate gene for syndromic hearing loss with IP-I. A mouse model with homozygous Zbtb10 frameshift variant resulted in embryonic lethality, suggesting the importance of this gene for early embryonic development. Our data highlight a wide spectrum of rare causative genes in patients with syndromic hearing loss, and demonstrate that WES analysis combined with phenotype similarity search is a valuable approach for clinical genetic testing of undiagnosed disease., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. This study was approved by the institutional ethics review board at the National Hospital Organization Tokyo Medical Center (R21-053), RIKEN Center for Integrative Medical Sciences (Yokohama H24-15(3)), and the Tokyo Medical and Dental University (O2015-503). All the experimental procedures for generation and use of Zbtb10-deficient mice were approved by National Hospital Organization Tokyo Medical Center (14-animal-05). Consent to participate: Studies were conducted only after patients or their parents signed informed consent forms to participate. Consent to publish: The participant has consented to the submission of the case report to the journal., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable form of osteonecrosis of the jaw that rarely occurs in patients using bone resorption inhibitors such as bisphosphonates (BPs). Then, extracellular vesicles (EVs) carry various signaling molecules, such as mRNAs, microRNAs (miRNAs), and proteins, and have attracted attention as intercellular communication tools. Recently, the role of EVs in communication between osteoclasts and surrounding bone cells has been confirmed. This study aimed to elucidate the effects of EVs derived from osteoclasts treated with zoledronic acid (ZA), one of the BPs on osteoclast function. EVs were isolated by ultracentrifugation of the culture supernatant of osteoclasts treated with ZA, and miRNAs were extracted from these EVs. Tartrate-resistant acid phosphatase staining of the ZA treated osteoclasts showed reduced osteoclastogenesis. In addition, pit assay showed that ZA significantly decreased the bone resorption capacity of osteoclasts. miRNA-seq analysis identified 11 upregulated and 5 downregulated differentially expressed genes (DEGs) in the miRNA of EVs derived from ZA-treated osteoclasts compared to EVs derived from osteoclasts not treated with ZA. qRT-PCR analysis confirmed the amount of these specific miRNAs, with miR-146a-5p, and miR-322-3p being significantly upregulated by ZA. Overexpression of miR-146a-5p in osteoclasts inhibited osteoclastogenesis and decreased the mRNA expression of osteoclast markers. In addition, Traf6 was identified as a candidate target gene of miR-146a-5p in several miRNA databases. Indeed, the overexpression of miR-146a-5p decreased the expression level of Traf6 in osteoclasts. Additionally, overexpression of miR-322-3p in the pre-osteoblast, MC3T3-E1 cells, resulted in a significant increase in the mRNA expression levels of Sp7. Our data indicate that BPs attenuate osteoclastogenesis by simultaneously altering the characteristics of osteoclast-derived EVs. Overexpression of miR-146a-5p and miR-322-3p influences osteoclast differentiation, and Traf6 is a target gene of miR-146a-5p. On the other hand, Overexpression of miR-322-3p affects osteoblast differentiation. We suggest that ZA-treated osteoclast-derived EVs may play an important role in osteoclast function and bone resorption., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

With the aging of society, the incidence of chronic kidney disease (CKD), a common cause of death, has been increasing. Transcription factor EB (TFEB), the master transcriptional regulator of the autophagy-lysosomal pathway, is regarded as a promising candidate for preventing various age-related diseases. However, whether TFEB in the proximal tubules plays a significant role in elderly CKD patients remains unknown. First, we found that nuclear TFEB localization in proximal tubular epithelial cells (PTECs) declined with age in both mice and humans. Next, we generated PTEC-specific Tfeb-deficient mice and bred them for up to 24 months. We found that TFEB deficiency in the proximal tubules caused metabolic disorders and occasionally led to apolipoprotein A4 (APOA4) amyloidosis. Supporting this result, we identified markedly decreased nuclear TFEB localization in the proximal tubules of elderly patients with APOA4 amyloidosis. The metabolic disturbances were accompanied with mitochondrial dysfunction due to transcriptional changes involved in fatty acid oxidation and oxidative phosphorylation pathways, as well as decreased mitochondrial clearance reflected by the accumulation of mitochondria-lysosome-related organelles, which depends on lysosomal function. These results shed light on the presumptive mechanisms of APOA4 amyloidosis pathogenesis and provide a therapeutic strategy for CKD-related metabolic disorders and APOA4 amyloidosis.

Reverse genetics systems for rotaviruses (RV) facilitate the generation of genetically engineered RVs by transfection of 11 plasmids encoding 11 genomic viral RNA segments. In addition to viral genome expression, overexpression of NSP2 and NSP5 has been used to increase the rescue efficiency of recombinant RVs. Here, we showed that the overexpression of nucleotide sequence-modified NSP2 and NSP5 enabled the rapid and efficient production of recombinant RVs. Using improved reverse genetics, we established a reverse genetics system for human and bovine RV clinical isolates, as well as laboratory strains of bovine RV (NCDV and UK) and porcine RV (Gottfried). In addition, we rescued low-replicating recombinant RVs carrying a mutant NSP4 lacking the double-layered particle-binding domain, which was deficient in the efficient production of mature virions. These advancements in reverse genetics enabled the generation of molecular clones of RV clinical isolates and recombinant RVs harboring critical amino acid mutations, offering a versatile platform for investigating RV biology and pathogenesis.IMPORTANCERecombinant rotavirus (RV) synthesis via reverse genetics relies on both the viral propagation capacity and the efficiency of the experimental system. Since the establishment of our reverse genetics system, several enhancements have been implemented to augment the rescue efficiency. Nevertheless, challenges persist in generating RV clinical strains and recombinant viruses with low replication capacities. Notably, this improved reverse genetics system successfully facilitated the establishment of molecular clones of human and bovine RV clinical isolates. Fecal samples from patients with RV typically harbor quasi-species or, occasionally, multiple genotypes of RV. In the present study, we performed the genetic sequencing of clinical viral strains during the early propagation stages in cultured cells. Subsequently, infectious viruses were synthesized, allowing the characterization of circulating viruses in nature. This approach provides valuable insights into the genetic diversity and dynamics of RV populations and contributes to a more comprehensive understanding of viral pathogenesis and evolution., Competing Interests: The authors declare no conflict of interest.

Competing Interests: The authors declare that they have no conflict of interest.

Objective: NF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS), often causing severe damage to the bilateral auditory function. Auditory brainstem implantation (ABI) provides hearing-impaired patients with an opportunity to reacquire auditory sensation through electrical stimulation of auditory neurons in the cochlear nucleus. However, ABI is not covered by public health insurance in Japan, leading to a large difference in financial burden compared to cochlear implantation (CI). The aim of the present study was to demonstrate the effectiveness of CI as an alternative to ABI for hearing reacquisition in patients with profound hearing loss caused by VS., Methods: To investigate the current situation of ABI and CI for hearing reconstruction in VS patients, we conducted a questionnaire survey of 102 facilities in Japan. Based on the responses to the questionnaire, a multicenter research group consisting of otolaryngologists and neurosurgeons was established. We collected detailed data on patients with VS who underwent ABI (n = 7, all NF2) and CI (n = 14 [nine NF2, and five non-NF2])., Results: Some sense of hearing was obtained in all patients but one with CI indicating the efficacy of CI and ABI for profound hearing loss caused by VS. The mean hearing levels were 45.4 dB HL in the ABI patients and 32.7 dB HL in the CI patients, indicating that CI was effective as an alternative to ABI., Conclusion: The results of the present study suggest the effectiveness of CI as an alternative to ABI for hearing reacquisition in patients with profound hearing loss caused by VS., (Copyright © 2024. Published by Elsevier B.V.)

Competing Interests: The authors declare that they have no conflict of interest.

Background: Patients with residual adolescent idiopathic scoliosis (AIS) and thoracolumbar/lumbar curves may present with progression after cessation of growth, with lateral translation as a major risk factor. Nonetheless, radiographic predictors and underlying mechanisms remain indefinite. This study aimed to determine these radiographic predictors and structural mechanisms in patients with residual AIS., Methods: Radiographic and clinical data were collected from 45 consecutive patients with preoperative residual AIS and thoracolumbar/lumbar Cobb angle >40° who subsequently underwent corrective surgery at our institution. Lateral translation was defined as intervertebral slippage ≥6 mm on computed tomography. Statistical analyses included Student's t-test, Pearson's correlation coefficients, receiver operating characteristic curve analysis, and multivariate logistic regression analysis., Results: Of 45 patients, 3 were male, whereas 42 were female, with a mean age of 40.6 ± 17.4 years. L3 slippage was observed in 21 patients, resulting in the categorization into the slippage and nonslippage cohorts. Multivariate logistic regression analysis revealed statistically significant disparities in the bilateral facet angles, facet joint opening, and facet joint vacuum phenomenon between the 2 cohorts. The receiver operating characteristic analysis determined a 20.5° cut-off value for predicting L3 slippage. In the nonslippage cohort, a strong correlation was particularly observed between L3 slippage and L2-L3 bridging., Conclusions: Facet joint instability, L4 tilt ≥20.5°, and L3 cranial vertebral bridging are predictive radiographic factors for L3 lateral translation in patients with residual AIS. Thus, patients exhibiting these characteristics require consistent follow-up or early surgical intervention before lateral translation occurs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Orientia tsutsugamushi (OT) is an obligate intracellular bacterium transmitted by larval trombiculid mites, responsible for scrub typhus in humans. In Japan, approximately 500 human cases are reported annually, with six major serotypes identified as Kato, Karp, Gilliam, Irie/Kawasaki, Shimokoshi, and Hirano/Kuroki. However, the prevalence of OT in Yamaguchi prefecture remains largely unknown. This study aimed to investigate the prevalence and serotypes of OT in wild rodents collected from eight locations within the prefecture. DNA was extracted from spleen and liver samples of 135 wild rodents collected between 2015 and 2024, and PCR was conducted to detect OT targeting the 56 kDa type-specific antigen gene. As a result, five individuals (3.7%) were detected positive for OT DNA. OT was successfully isolated from two of the five rodents and characterized by multi-locus sequence analysis (MLSA) based on 11 housekeeping genes. The MLSA results indicated that both isolates clustered with OT strain Ikeda (JG serotype). Additionally, we performed a serological test on 117 serum samples from wild rodents using the indirect immune peroxidase test. The results showed that 59.8% (n = 70/117) of the rodents had antibodies against OT, with 73% (n = 51/70) showing the highest titer against the OT strains Gilliam (Gilliam serotype) and Ikeda (JG serotype), known to be transmitted by Leptotrombidum pallidum mites. Overall, the present study identified the OT serotypes and potential primary vector species in Yamaguchi prefecture, emphasizing the need for further surveillance, particularly, in humans., (© 2024 The Societies and John Wiley & Sons Australia, Ltd.)

Objective: The objective of this study was to determine whether a reduction in the retrocrural space (RCS) area is a risk factor for postoperative ileus (POI) in patients with adult spinal deformity (ASD) treated with spinal corrective surgery., Methods: In total, 100 patients (mean age 67.5 ± 8.3 years, 9 males and 91 females) with ASD treated with spinal corrective surgery were included in this study. Spinal parameters, including thoracolumbar kyphosis (TLK), and RCS area were measured pre- and postoperatively. The change (Δ) in spinal parameters was calculated. The percent change between pre- and postoperative RCS areas was calculated as ΔRCS. Patients were identified as having POI if they exhibited both gastrointestinal symptoms and radiographic findings. Each parameter was compared between patients with and without POI. Multivariable logistic regression analysis was performed with development of POI as the dependent variable., Results: The incidence of POI was 11.0%. The RCS area was significantly smaller in the POI group than in the non-POI group (p < 0.001). Multivariable logistic regression analysis revealed that ΔTLK and ΔRCS were risk factors for POI (p = 0.029 and p = 0.033, respectively)., Conclusions: A reduction in the RCS area is a risk factor for the development of POI after corrective spinal surgery in patients with ASD. Overcorrection of the thoracolumbar junction should be avoided to prevent POI.

The live attenuated vaccine (P7-P8 strain) against cyprinid herpesvirus 2 (CyHV-2) infection of goldfish shows high protective efficacy. However, the underlying immune mechanism induced by P7-P8 vaccination remains unknown. It is known that the fish survived in the primary infection with CyHV-2 by the virus non-permissive high temperature (HT) water treatment elicit immunity against secondary virus challenge. In this study, the immunity induced by the P7-P8 vaccine was compared with that by HT treatment. To further explore the immunological responses of cyprinids, in addition to goldfish Carassius auratus, susceptible isogenic ginbuna C. auratus langsdorfii was included in this study. In the primary immune response, cyprinids were vaccinated with P7-P8, or treated with HT. In the secondary immune response, cyprinids were challenged with the virulent CyHV-2. The percentage dynamics of CD4-1 and CD8α positive lymphocytes were determined during the primary and secondary immune responses of the two cyprinids. Blood plasma was sampled to assess the anti-CyHV-2 IgM antibody titers. The vaccination with P7-P8 and HT-treatment induced high protection immunity in the cyprinids with relative percentage survival of over 88 % against virulent virus challenge. Our finding shows that the CD8α positive lymphocytes rather than CD4-1 positive lymphocytes play an important role in the secondary immune responses of cyprinids vaccinated with P7-P8. The CD4-1 positive lymphocytes rather than CD8α positive lymphocytes play an important role in the secondary immune responses of cyprinids treated with HT. The antibody titer of vaccinated cyprinids did not increase greatly even after virulent virus challenge. The results suggest the vaccine activates the CD8α cells and the secondary cell-mediated immunity. The differences in the induced immunity mechanisms in fish by the two measures might be based on the virus either being an avirulent virus form that cannot evade host responses or a virulent virus form that cannot propagate at non-permissive temperature., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Emerging polar skyrmion crystals (SkX) have raised much interest for technological applications owing to their nontrivial topologies of electric dipoles, quasiparticle-like behaviors, and unique electrical responses. Understanding SkX defects, especially dislocations, is crucial for their unique lattice dynamics and responses; however, it still remains elusive. Here, we have not only demonstrated that a SkX dislocation exhibits an anomalously deformed core structure with over 50% elongation of skyrmions but also discovered that Volterra's elasticity theory of dislocation is broken down in SkX. Our phase-field simulation reveals that these distinct features of SkX dislocation arise from a rigid to soft quasiparticle transition of skyrmions depending on the electric field and temperature. In SkX, there exist inherent mechanics that mitigate the mismatch by both migration and deformation of skyrmions. This work provides novel insights into a new class of lattice mechanics and related functionality arising from the unique properties of quasi-particle SkX.

The renoprotective effects of SLC5A2/SGLT2 (solute carrier 5 (sodium/glucose cotransporter), member 2) inhibitors have recently been demonstrated in non-diabetic chronic kidney disease (CKD), even without overt albuminuria. However, the mechanism underlying this renoprotection is largely unclear. We investigated the renoprotective mechanisms of the SLC5A2 inhibitor empagliflozin with a focus on ALB (albumin) reabsorption and macroautophagy/autophagy in proximal tubules using wild-type or drug-inducible lrp2/Megalin or atg5 knockout mice with high-fat diet (HFD)-induced obesity or 5/6 nephrectomy that elevated intraglomerular pressure without overt albuminuria. Empagliflozin treatment of HFD-fed mice reduced several hallmarks of lipotoxicity in the proximal tubules, such as phospholipid accumulation in the lysosome, inflammation and fibrosis. Empagliflozin, which decreases intraglomerular pressure, not only reduced the HFD-induced increase in ALB reabsorption via LRP2 in the proximal tubules ( i.e . total nephron ALB filtration), as assessed by urinary ALB excretion caused by genetic ablation of Lrp2 , but also ameliorated the HFD-induced imbalance in circulating ALB-bound fatty acids. Empagliflozin alleviated the HFD-induced increase in autophagic demand and successfully prevented autophagic stagnation in the proximal tubules. Similarly, empagliflozin decreased ALB exposure and autophagic demand in 5/6 nephrectomized mice. Finally, empagliflozin reduced HFD-induced vulnerability to ischemia-reperfusion injury, whereas LRP2 blockade and atg5 ablation separately diminished this effect. Our findings indicate that empagliflozin reduces ALB exposure and prevents autophagic stagnation in the proximal tubules even without overt albuminuria. Autophagy improvement may be critical for the renoprotection mediated by SLC5A2 inhibition.

Background : Sarcopenia, the age-related loss of muscle mass, is a negative prognostic factor in gastrointestinal cancer. Sarcopenia combined with visceral obesity (sarcopenic obesity) is associated with poor outcomes. We explored the influence of obesity and other factors on the prognosis of patients with colorectal cancer diagnosed with sarcopenia. Methods : We enrolled 211 patients with colorectal cancer diagnosed with preoperative sarcopenic obesity who underwent radical resection at Osaka University Hospital between January 2009 and January 2012. Muscle mass was assessed using the psoas muscle mass index. Obesity was evaluated by measuring the visceral fat area in the umbilical region. Patients were categorized into two groups: sarcopenia with obesity (SO) and sarcopenia without obesity (non-SO). Overall survival, cancer-specific survival, and cancer-related relapse-free survival (CRRFS) were compared between the two groups. Patient characteristics, including age, sex, body mass index, serum albumin, C-reactive protein, tumor markers, prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and geriatric nutritional risk index (GNRI), were also analyzed. Results : CRRFS was significantly shorter in the SO group than in the non-SO group ( p = 0.028). PNI, mGPS, and GNRI were not identified as significant prognostic factors for CRRFS. Multivariate analysis highlighted sarcopenic obesity, elevated carcinoembryonic antigen levels, and unfavorable histological types as significant predictors of poor CRRFS outcomes. Conclusions : Sarcopenic obesity is an independent predictor of poor prognosis in patients with CRC. Thus, interventions aimed at increasing muscle mass and reducing visceral fat could potentially improve the prognosis of these patients.

Objective: This study aims to comprehend the natural history of adolescent idiopathic scoliosis (AIS) patients and determine risk factors for facet joint bridging in adolescent-onset adult idiopathic scoliosis with thoracolumbar/lumbar (TL/L) curves., Methods: We included 50 patients with residual AIS with TL/L curves (3 males, 47 females; age 41.5 ± 17.3 years, TL/L Cobb angle 59.4 ± 11.8°). They were >20 years old and diagnosed with AIS during their adolescence. Radiographic parameters were measured, and facet joint bridging was defined from axial computed tomography images., Results: The sagittal vertical axis (SVA) significantly increased with age (r = 0.71, P < 0.01). Coronal Cobb angle of the TL/L curve, L4 tilt, C7 translation, lumbar lordosis (LL), pelvic incidence-LL, pelvic tilt, and thoracolumbar kyphosis were also correlated to age (P < 0.05). There were significant differences in age, SVA, pelvic incidence-LL, vertebral bridging, facet tropism, and apical vertebral rotation (AVR) between the facet joint bridging group (n = 10) and the non-facet joint bridging group (n = 40). In the multivariate logistic regression analysis, SVA, vertebral bridging, and AVR emerged as notable risk determinants for facet joint bridging. The threshold for facet joint bridging based on SVA was 2.1 cm (area under the curve: 0.801; sensitivity = 90%; specificity = 65%)., Conclusions: This research revealed that large SVA, the presence of vertebral bridging, and large AVR are associated with facet joint bridging in adolescent-onset adult idiopathic scoliosis patients with TL/L curves. The cutoff value for facet joint bridging based on SVA was 2.1 cm., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data., Materials and Methods: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism., Results: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V 60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism., Conclusion: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Dental pulp stem cells (DPSCs) demonstrate high proliferative and multilineage differentiation potential. As previously reported, the helioxanthin derivative 4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2,3-b]pyridine-2-carboxamide (TH) has been demonstrated to induce the osteogenic differentiation of DPSCs. However, the mechanism of osteogenesis induced by TH in DPSCs remains unknown. The objective of this study was to identify functional extracellular vesicle (EV) microRNAs (miRNAs), and the principal genes involved in the TH-induced osteogenesis of DPSCs. DPSCs were derived from dental pulp extracted from the third molars of three healthy subjects, and were cultured with or without TH. miRNAs were extracted from DPSC-derived EVs. The gene expression patterns of mRNA and miRNA were compared using RNA-Seq and miRNA-Seq. To investigate miRNA/mRNA interacting networks, functional analyses were performed by Ingenuity Pathway Analysis. Alkaline phosphatase (ALP) staining demonstrated that treatment with TH resulted in enhanced ALP activity in DPSCs after 7 days. The expression levels of ALP and type 1 collagen alpha 1 were significantly higher in TH-induced DPSCs on day 7. RNA-Seq and miRNA-Seq analyses identified 869 differentially expressed genes (DEGs) and 18 miRNA-DEGs. Gene Ontology analysis of the mRNA-Seq results showed that TH induced several biological activities associated with signal transduction, cell adhesion, and cell differentiation. Integrated miRNA-mRNA analyses showed that these miRNAs contain the targeting information of 277 mRNAs of the DEGs. Among them, 17 target genes known to be involved in the differentiation of osteoblasts, and 24 target genes known to be involved in the differentiation of bone cells were identified. Quantitative real-time PCR showed that WNT5a expression in DPSCs was upregulated by 48 h of TH treatment. Upstream regulator analysis indicated that WNT3a , FOS , and RAC1 may be responsible for gene expression changes in DPSCs after TH treatment. EV miRNA regulatory networks might play crucial roles in TH-induced osteogenic differentiation of DPSCs. Our results presented herein offer valuable insights that will facilitate further research into the mechanism of osteogenesis of DPSCs, which is expected to lead to the clinical application of TH-induced DPSCs for bone regeneration. Furthermore, EVs derived from TH-induced DPSCs might be useful as therapeutic tools for bone defects.

Background and Aims: Colorectal polyps resected by cold snare polypectomy (CSP) are rarely diagnosed as colorectal cancer (CRC). We aimed to investigate the prevalence, clinical features, and prognosis of patients with CRC resected by CSP., Subjects: Patients with colorectal polyps treated with CSP between 2018 and 2022 were enrolled and regularly followed up (median observation period: 30.6 months). Logistic regression analysis and decision tree analysis were employed to investigate the clinical features of the patients., Results: A total of 5,064 colorectal polyps from 2,530 patients were resected by CSP. Of these, 0.24% were diagnosed as CRC; however, no patients died due to CRC. eGFR was an independent risk factor for the presence of CRC (unit 10, OR 0.716, 95%CI 0.525-0.973, P=0.0323) and its optimal cut-off value was 59.9 mL/min/1.73 m 2 . The decision-tree analysis revealed that 2.03% of patients with creatinine ≥ 1.0 mg/dL had CRC., Conclusion: CRC was diagnosed in 0.24% of the polyps; however, no patients died due to CRC. eGFR <60 mL/min/1.73 m 2 and creatinine >1.0 mg/dL were associated with CRC. Thus, colorectal polyps should be carefully examined in patients with chronic kidney disease.

The STING (stimulator of interferon genes) pathway is one of the pathways that regulate innate immunity, and the extracellular hydrolytic enzyme ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) has been identified as its dominant negative regulator. Since activation of the innate immune system is a promising strategy for the treatment of various infectious diseases and cancers, ENPP1 inhibitors have attracted great attention as candidate drugs. We have previously identified small-molecule ENPP1 inhibitors having a [1,2,4]triazolo[1,5-a]pyrimidine scaffold by means of chemical screening using a fluorescence probe, TG-mAMP. In this study, we evaluated the structure-activity relationships of the hit and lead compounds in detail, and succeeded in developing compounds that strongly and selectively inhibit ENPP1 not only in vitro, but also in cellular systems., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In a randomized phase II/III trial (JCOG1008), weekly cisplatin (40 mg/m 2 ) was non-inferior to 3-weekly cisplatin (100 mg/m 2 ) for postoperative high-risk head and neck cancer. We investigated how acute kidney injury (AKI), a major dose-limiting toxicity effect of cisplatin, affects overall survival (OS)., Methods: We analyzed 251 patients from JCOG1008 receiving chemoradiotherapy. AKI was defined based on AKI Network criteria (serum creatinine increase of ≥0.3 mg/dL or ≥1.5-fold [≥ stage I]) within 30 days after completing chemoradiotherapy. OS in the two arms was compared according to AKI development using the log-rank test., Results: The total incidence of AKI was lower in the weekly arm than in the 3-weekly arm (38/122 [31.1%] vs. 56/129 [43.4%]). Additionally, stage II/III AKI occurred less frequently in the weekly arm than in the 3-weekly arm (8/122 [6.6%] vs. 19/129 [14.7%]). Cisplatin doses were similar in the weekly arm for patients with and without AKI (median, 238.6 mg/m 2 vs. 239.2 mg/m 2 ; p = 0.94), but lower in the 3-weekly arm for those who developed AKI (median, 276.3 mg/m 2 vs. 297.4 mg/m 2 ; p = 0.007). In the weekly arm, there was no difference in OS between patients with and without AKI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.53 to 2.10). However, in the 3-weekly arm, patients with AKI had poorer OS than those without AKI (HR, 1.83; 95% CI, 1.04 to 3.21)., Conclusions: In this supplementary analysis of JCOG1008 data, AKI impacted the OS of patients with head and neck cancer undergoing postoperative chemoradiotherapy in the 3-weekly arm but not in the weekly arm. Our results further endorse the utilization of weekly cisplatin at 40 mg/m 2 in this setting., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background/aim: Transanal endoscopic local excision requires fine operation in a very narrow space in the rectum. We report a case in which the use of surgical instruments with a multi-jointed structure allowed safe resection of a lesion with a stable field of view, resulting in preservation of postoperative function., Case Report: The patient was a 49-year-old man who had a rectal neuroendocrine tumor (NET) (G1) with erosive changes in the lower rectum. Preoperative imaging showed no evidence of surrounding lymph node or distant metastasis; thus, we performed a transanal endoscopic local excision of the tumor. After positioning the patient under general anesthesia and securing the field of view in the intra-rectal cavity, the flexion of the surgical instruments with a multi-jointed structure was used to secure the operating space to not interfere with the camera and the surgeon's right hand. The operating field was developed, and the tumor was incised by stable traction. After the excision, the needle was advanced in the direction of the intestinal axis using the multi-jointed holder, and continuous suturing was performed. The patient has no recurrence without any defecation disorder., Conclusion: The use of multi-jointed surgical instruments in transanal endoscopic excision of rectal tumors can provide a stable operative field and preserve postoperative function. The advanced flexibility of these instruments allows precise manipulation in the narrow rectal space, resulting in successful tumor resection with minimal invasiveness and no postoperative complications. These findings suggest that multi-jointed instruments are valuable for enhancing the safety and efficacy of minimally invasive rectal surgery., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)