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Kabuki syndrome (KS) is a genetic disorder caused by gene mutations in either lysine-specific methyltransferase 2D (KMT2D) or lysine demethylase 6A (KDM6A). This congenital disorder exhibits characteristic facial features, developmental delays in psychomotor skills, and skeletal abnormalities. Moreover, it is classified as a congenital immunodeficient disorder under the category of combined immunodeficiency, leading to hypogammaglobulinemia and the onset of autoimmune diseases. Here, we present the first case of KS complicated by idiopathic pulmonary hemosiderosis (IPH). The KS patient, a 2-year-old Japanese girl with a history of hypoplastic left heart syndrome and recurrent bacterial infection, developed severe respiratory distress and anemia. She had autoimmune hemolytic anemia and gouty nephropathy. Hemophagocytic macrophages with hemosiderin ingestion were identified in bronchoalveolar lavage fluid, excluding differential diagnoses and leading to the diagnosis of idiopathic pulmonary hemosiderosis. Intravenous prednisolone (2 mg/kg/day) was administered, but symptoms did not improve. However, pulmonary hemorrhage disappeared with methylprednisolone pulse therapy. IPH warrants consideration in cases where individuals with KS manifest idiopathic pneumonia and concurrent anemia.

Abstract Intraluminal tumor in the azygos vein is a rare disease that can cause superior vena cava (SVC) syndrome. Radiotherapy and endovascular stenting with or without chemotherapy are reported to have a high clinical success rate for the management of SVC syndrome with malignancy, but a poor survival rate. Here, we report a 69‐year‐old man who presented with swelling of the face and upper extremities, who was diagnosed with SVC syndrome caused by an intraluminal tumor in the azygos vein. Enhanced chest computed tomography revealed an intraluminal mass with a filling defect from the azygos vein to the SVC, with no extravascular extension or dissemination of the primary tumor. Surgical resection of the mass en bloc with the azygos vein and SVC reconstruction was performed. A poorly differentiated carcinoma was diagnosed on postoperative pathological evaluation. Twelve months after resection, the patient was well with no signs of recurrent disease. This case highlights that surgical resection should be considered as a treatment of choice for the management of SVC syndrome caused by an intraluminal malignancy in the azygos vein.

BackgroundRecently, cases of overlapping encephalitis caused by anti-N-methyl-D-aspartate receptor (anti-NMDAR) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have been reported, and their clinical characteristics are gradually becoming clear. Acute-phase treatment typically involves the use of steroids, and although some studies have suggested that steroids can be effective, the extent of their efficacy has not yet been fully explored.Case presentationWe present the case of a 25-year-old man with anti-NMDAR and anti-MOG antibody overlapping encephalitis who showed considerable improvement after steroid treatment. To gain a deeper understanding of the efficacy of steroids in managing this condition, we conducted a literature review of cases of anti-NMDAR and anti-MOG antibody double-positive encephalitis that were treated with steroids during the acute phase. Thirteen cases were analyzed, including a new case diagnosed at our hospital. All patients showed improvement after receiving steroid treatment in the acute phase. Ten patients did not have any sequelae, and nine of them showed a rapid or major response during the acute phase. In contrast, three patients experienced sequelae (mild cognitive decline, visual impairment, and memory impairment, respectively), with their response to steroids in the acute phase being slow or limited. Relapses occurred in five patients, in one patient during steroid tapering, and in another two patients after cessation of steroids.ConclusionSteroid therapy can be effective in the acute stage of anti-NMDAR and anti-MOG antibody overlapping encephalitis. A positive prognosis may be expected in patients who experience substantial improvement with steroid therapy during the acute phase.

Abstract Pulmonary endarterectomy (PEA) is a standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH combined with bronchial obstruction by a tumor is rare but should be assessed carefully because PEA for obstructed segments can be less therapeutic and make the subsequent surgical resection challenging. This report describes a case of CTEPH with bronchial obstruction by a typical carcinoid tumor in a 75‐year‐old man. On‐site evaluation and removal of the obstructive tumor were performed bronchoscopically, increasing the effectiveness of subsequent PEA for all affected pulmonary segments. This report illustrates a PEA strategy to treat CTEPH with bronchial tumor obstruction.

In this study, LES calculations by OpenFOAM were performed using five blade models with different blade thicknesses (original, quarter, half, 3-quarters, and filled) to investigate the characteristics of separated and reattaching flow between blades of two-dimensional cascade. The results showed that the type of separation changes from leading edge separation (original - half models) to on-blade separation (3-quarters and filled models) as the blade thickness increases. The size of the separation bubbles and the distribution of mean and RMS values of pressure on and between the blades varied continuously within the three models for leading edge separation and within the two models for on-blade separation, respectively. The changes in the vortex structure were captured by considering the spectral shape of pressure between the blades. In the case of leading edge separation, vortex shedding, merging, reattachment, and collapsing were detected while in the case of on-blade separation, they were hardly detected. In the case of leading edge separation, the vortex merging prevented the increase of the RMS value of the pressure. In the case of leading edge separation, with increasing the blade thickness, two dimensionality of the vortex was weakened and irregularity of the vortex structure was strengthened, and therefore, the periodicity of the vortex merging was weakened.

ABSTRACTAntibodies are one of the predominant treatment modalities for various diseases. To improve the characteristics of a lead antibody, such as antigen-binding affinity and stability, we conducted comprehensive substitutions and exhaustively explored their sequence space. However, it is practically unfeasible to evaluate all possible combinations of mutations owing to combinatorial explosion when multiple amino acid residues are incorporated. It was recently reported that a machine-learning guided protein engineering approach such as Thompson sampling (TS) has been used to efficiently explore sequence space in the framework of Bayesian optimization. For TS, over-exploration occurs when the initial data are biasedly distributed in the vicinity of the lead antibody. We handle a large-scale virtual library that includes numerous mutations. When the number of experiments is limited, this over-exploration causes a serious issue. Thus, we conducted Monte Carlo Thompson sampling (MTS) to balance the exploration-exploitation trade-off by defining the posterior distribution via the Monte Carlo method and compared its performance with TS in antibody engineering. Our results demonstrated that MTS largely outperforms TS in discovering desirable candidates at an earlier round when over-exploration occurs on TS. Thus, the MTS method is a powerful technique for efficiently discovering antibodies with desired characteristics when the number of rounds is limited.

Introduction Metastasectomy of oligometastatic prostate cancer has the potential to contribute to improving prognosis. We report on a case of metastasectomy of solitary liver tumor after radical prostatectomy. Case presentation An 80‐year‐old man underwent radical prostatectomy for prostate cancer, followed by radiotherapy after the operation because of increased serum prostate‐specific antigen levels of 0.529 ng/mL. Levels increased further to 0.997 ng/mL even after salvage therapy. The patient then received androgen deprivation therapy. Levels remained stable for 3 years, but rapidly increased to 19.781 ng/mL in the following 6 months. Abdominal computed tomography revealed a solitary liver tumor, and no metastasis to other sites was identified. The patient underwent liver segmentectomy. Microscopic examination of excised specimens revealed prostate cancer cells. Five years after surgery, serum prostate‐specific antigen maintained to the lowest level so far. Conclusion Metastasectomy might be a beneficial therapeutic option to improve the prognosis for solitary metastasis from prostate cancer.

Oligodendrocytes (OCs) form myelin around axons, which is dependent on neuronal activity. This activity-dependent myelination plays a crucial role in training and learning. Previous studies have suggested that neuronal activity regulates proliferation and differentiation of oligodendrocyte precursor cells (OPCs) and myelination. In addition, deficient activity-dependent myelination results in impaired motor learning. However, the functional response of OC responsible for neuronal activity and their pathological changes is not fully elucidated. In this research, we aimed to understand the activity-dependent OC responses and their different properties by observing OCs using in vivo two-photon microscopy. We clarified that the Ca2+ activity in OCs is neuronal activity dependent and differentially regulated by neurotransmitters such as glutamate or adenosine triphosphate (ATP). Furthermore, in 5-month-old mice models of Alzheimer’s disease, a period before the appearance of behavioral abnormalities, the elevated Ca2+ responses in OCs are ATP dependent, suggesting that OCs receive ATP from damaged tissue. We anticipate that our research will help in determining the correct therapeutic strategy for neurodegenerative diseases beyond the synapse.

This study investigated the effects of a long noncoding RNA, nuclear paraspeckle assembly transcript 1 (NEAT1) variant 1 (NEAT1v1) on drug resistance in liver cancer cell lines. NEAT1 knockdown activated mitogen-activated protein kinase (MAPK) signaling pathways, including MAPK kinase (MEK)/extracellular signal-regulated kinase (ERK), but suppressed AKT. Moreover, NEAT1 knockdown sensitized liver cancer cells to sorafenib and lenvatinib, both clinically used for treating hepatocellular carcinoma, whereas it conferred resistance to an AKT-targeted drug, capivasertib. NEAT1v1 overexpression suppressed MEK/ERK and activated AKT, resulting in resistance to sorafenib and lenvatinib and sensitization to capivasertib. Superoxide dismutase 2 (SOD2) knockdown reverted the effects of NEAT1v1 overexpression on the sensitivity to the molecular-targeted drugs. Although NEAT1 or SOD2 knockdown enhanced endoplasmic reticulum (ER) stress, concomitant with the suppression of AKT, taurodeoxycholate, an ER stress suppressor, did not restore AKT activity. Although further in vivo and clinical studies are needed, these results suggested that NEAT1v1 switches the growth modality of liver cancer cell lines from MEK/ERK-dependent to AKT-dependent mode via SOD2 and regulates sensitivity to the molecular-targeted drugs independent of ER stress.

Introduction: Assessing the stage of liver fibrosis during the diagnosis and follow-up of patients with diffuse liver disease is crucial. The tissue structure in the fibrotic liver is reflected in the texture and contrast of an ultrasound image, with the pixel brightness indicating the intensity of the echo envelope. Therefore, the progression of liver fibrosis can be evaluated non-invasively by analyzing ultrasound images.Methods: A convolutional-neural-network (CNN) classification of ultrasound images was applied to estimate liver fibrosis. In this study, the colorization of the ultrasound images using echo-envelope statistics that correspond to the features of the images is proposed to improve the accuracy of CNN classification. In the proposed method, the ultrasound image is modulated by the 3rd- and 4th-order moments of pixel brightness. The two modulated images and the original image were then synthesized into a color image of RGB representation.Results and Discussion: The colorized ultrasound images were classified via transfer learning of VGG-16 to evaluate the effect of colorization. Of the 80 ultrasound images with liver fibrosis stages F1–F4, 38 images were accurately classified by the CNN using the original ultrasound images, whereas 47 images were classified by the proposed method.

Introduction Multidrug chemoimmunotherapy with rituximab, high-dose methotrexate, procarbazine and vincristine (R-MPV) is a standard therapy for younger patients with primary central nervous system lymphoma (PCNSL); however, prospective data regarding its use in elderly patients are lacking. This multi-institutional, non-randomised, phase II trial will assess the efficacy and safety of R-MPV and high-dose cytarabine (HD-AraC) for geriatric patients with newly diagnosed PCNSL.Methods and analysis Forty-five elderly patients will be included. If R-MPV does not achieve complete response, the patients will undergo reduced-dose, whole-brain radiotherapy comprising 23.4 Gy/13 fractions, followed by local boost radiotherapy comprising 21.6 Gy/12 fractions. After achieving complete response using R-MPV with or without radiotherapy, the patients will undergo two courses of HD-AraC. All patients will undergo baseline geriatric 8 (G8) assessment before HD-AraC and after three, five and seven R-MPV courses. Patients with screening scores of ≥14 points that decrease to

One of the challenges in clinical translation of cell-replacement therapies is the definition of optimal cell generation and storage/recovery protocols which would permit a rapid preparation of cell-treatment products for patient administration. Besides, the availability of injection devices that are simple to use is critical for potential future dissemination of any spinally targeted cell-replacement therapy into general medical practice. Here, we compared the engraftment properties of established human-induced pluripotent stem cells (hiPSCs)-derived neural precursor cell (NPCs) line once cells were harvested fresh from the cell culture or previously frozen and then grafted into striata or spinal cord of the immunodeficient rat. A newly developed human spinal injection device equipped with a spinal cord pulsation-cancelation magnetic needle was also tested for its safety in an adult immunosuppressed pig. Previously frozen NPCs showed similar post-grafting survival and differentiation profile as was seen for freshly harvested cells. Testing of human injection device showed acceptable safety with no detectable surgical procedure or spinal NPCs injection-related side effects.

The critical requirements in developing clinical-grade human-induced pluripotent stem cells–derived neural precursors (hiPSCs-NPCs) are defined by expandability, genetic stability, predictable in vivo post-grafting differentiation, and acceptable safety profile. Here, we report on the use of manual-selection protocol for generating expandable and stable human NPCs from induced pluripotent stem cells. The hiPSCs were generated by the reprogramming of peripheral blood mononuclear cells with Sendai-virus (SeV) vector encoding Yamanaka factors. After induction of neural rosettes, morphologically defined NPC colonies were manually harvested, re-plated, and expanded for up to 20 passages. Established NPCs showed normal karyotype, expression of typical NPCs markers at the proliferative stage, and ability to generate functional, calcium oscillating GABAergic or glutamatergic neurons after in vitro differentiation. Grafted NPCs into the striatum or spinal cord of immunodeficient rats showed progressive maturation and expression of early and late human-specific neuronal and glial markers at 2 or 6 months post-grafting. No tumor formation was seen in NPCs-grafted brain or spinal cord samples. These data demonstrate the effective use of in vitro manual-selection protocol to generate safe and expandable NPCs from hiPSCs cells. This protocol has the potential to be used to generate GMP (Good Manufacturing Practice)-grade NPCs from hiPSCs for future clinical use.

Abstract Background Kampo prescriptions can cause drug‐induced lung injury (DLI) and acute respiratory distress syndrome (ARDS). However, severe respiratory failure induced by Otsujito (OJT) is extremely rare. High‐dose steroid pulse therapy is generally given to patients with severe DLI. Case Presentation A 63‐year‐old man with respiratory distress was admitted to our hospital. The patient was diagnosed with severe ARDS caused by OJT, which had been prescribed 4 weeks prior to admission. Thus, OJT was discontinued, and intensive care for ARDS, including ventilation and prone positioning, was implemented. His respiratory condition rapidly improved after treatment with an initial methylprednisolone dose (1.5 mg/kg/day). He was extubated on day 4 and discharged on day 16. The steroid dose was gradually reduced and discontinued by day 116. Conclusion A severe case of ARDS caused by OJT was successfully treated with low‐dose steroids and specialized intensive care.

Anti-N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis is caused by a reversible inhibition of ion channel actions by autoantibodies and is associated with a relatively good prognosis. Pathological findings of NMDAR encephalitis usually do not show neurophagorous nodules, but rare or mild inflammatory infiltration. We report a patient of small cell lung cancer (SCLC)-related paraneoplastic encephalitis with NMDAR antibodies, a cytotoxic T-cell-mediated pathology of the brain, and a rapid clinical course. This case highlights that the neuropathological diversity of NMDAR encephalitis may be even broader than previously thought and that NMDAR antibodies may also be found in various pathological conditions with a vigorous immune response.

The multiple-ion-probe method detects flames using a plurality of ion probes installed on the wall of a combustion chamber and by reconstructing the dynamic behavior of the flame front along the wall. Although this method is effective only close to the wall, it can indirectly aid in visualizing flame propagation behavior. Because this method has an extremely high time resolution, it can accurately measure high-speed phenomena such as knocking in a spark-ignition engine. This study aims to establish a method to automatically determine the characteristics of combustion for each mixture using the acquired data from a multiple-ion-probe measurement system; various propagating flames in combustible mixtures with different compositions were used. The combustible mixture was composed of methane or LPG as the fuel and argon or nitrogen as the diluent. A stoichiometric mixture of fuel and oxygen was diluted by changing the diluent ratio to prepare fourteen types of mixtures for investigation. From the obtained individual experimental data, twelve types of scalar features were extracted and compared with the experimental data. We compared the scalar features extracted from the output data of the multiple-ion probe with the different combustion modes obtained in the series of experiments; we found that a few of the features strongly responded to specific propagation states. Thus, we confirmed that by using the features, it is possible to determine the characteristics of the propagation states; such characteristics are difficult to determine merely from the flame surface shape reconstructed from the multiple-ion-probe data.

Introduction: During exposure of the carotid arteries, embolism from the surgical site is recognized as a primary cause of neurological deficits or new cerebral ischemic lesions following carotid endarterectomy (CEA), and associations have been reported between histological neovascularization in the carotid plaque and both plaque vulnerability and the development of artery-to-artery embolism. Superb microvascular imaging (SMI) enables accurate visualization of neovessels in the carotid plaque without the use of intravenous contrast. This study aimed to determine whether preoperative SMI ultrasound for cervical carotid artery stenosis predicts the development of microembolic signals (MES) on transcranial Doppler (TCD) during exposure of the carotid arteries in CEA. Methods: Preoperative cervical carotid artery SMI ultrasound followed by CEA under TCD monitoring of MES in the ipsilateral middle cerebral artery was conducted in 70 patients previously diagnosed with internal carotid artery stenosis (defined as ≥70%). First, observers visually identified intraplaque microvascular flow (IMVF) signals as moving enhancements located near the surface of the carotid plaque within the plaque on SMI ultrasonograms. Next, regions of interest (ROI) were manually placed at the identified IMVF signals (or at arbitrary places within the plaque when no IMVF signals were identified within the carotid plaque) and the carotid lumen, and time-intensity curves of the IMVF signal and lumen ROI were generated. Ten heartbeat cycles of both time-intensity curves were segmented into each heartbeat cycle based on gated electrocardiogram findings and averaged with respect to the IMVF signal and lumen ROI. The difference between the maximum and minimum intensities (ID) was calculated based on the averaged IMVF signal (IDIMVF) and lumen (IDl) curves. Finally, the ratio of IDIMVF to IDl was calculated. Results: MES during exposure of the carotid arteries were detected in 17 patients (24%). The incidence of identification of IMVF signals was significantly greater in patients with MES (94%) than in those without (57%; p = 0.0067). The IDIMVF/IDl ratio was significantly greater in patients with MES (0.108 ± 0.120) than in those without (0.017 ± 0.042; p < 0.0001). The specificity and positive predictive value for the IDIMVF/IDl ratio for prediction of the development of MES were significantly higher than those for the identification of IMVF signals. Logistic regression analysis revealed that only the IDIMVF/IDl ratio was significantly associated with the development of MES (95% CI 101.1–3,628.9; p = 0.0048). Conclusion: Preoperative cervical carotid artery SMI ultrasound predicts the development of MES on TCD during exposure of the carotid arteries in CEA.

Abstract Molecular evolution is an important step in the development of therapeutic antibodies. However, the current method of affinity maturation is overly costly and labor-intensive because of the repetitive mutation experiments needed to adequately explore sequence space. Here, we employed a long short term memory network (LSTM)—a widely used deep generative model—based sequence generation and prioritization procedure to efficiently discover antibody sequences with higher affinity. We applied our method to the affinity maturation of antibodies against kynurenine, which is a metabolite related to the niacin synthesis pathway. Kynurenine binding sequences were enriched through phage display panning using a kynurenine-binding oriented human synthetic Fab library. We defined binding antibodies using a sequence repertoire from the NGS data to train the LSTM model. We confirmed that likelihood of generated sequences from a trained LSTM correlated well with binding affinity. The affinity of generated sequences are over 1800-fold higher than that of the parental clone. Moreover, compared to frequency based screening using the same dataset, our machine learning approach generated sequences with greater affinity.

Induced pluripotent stem cell (iPSC) derived dopaminergic neurons are a promising source for cell-based Parkinson’s disease (PD) therapy. Here the authors report a comprehensive pre-clinical evaluation of the safety and efficacy of dopaminergic progenitors derived from a clinical-grade human iPSC line.

High-frame-rate imaging with a clutter filter can clearly visualize blood flow signals and provide more efficient discrimination with tissue signals. In vitro studies using clutter-less phantom and high-frequency ultrasound suggested a possibility of evaluating the red blood cell (RBC) aggregation by analyzing the frequency dependence of the backscatter coefficient (BSC). However, in in vivo applications, clutter filtering is required to visualize echoes from the RBC. This study initially evaluated the effect of the clutter filter for ultrasonic BSC analysis for in vitro and preliminary in vivo data to characterize hemorheology. Coherently compounded plane wave imaging at a frame rate of 2 kHz was carried out in high-frame-rate imaging. Two samples of RBCs suspended by saline and autologous plasma for in vitro data were circulated in two types of flow phantoms without or with clutter signals. The singular value decomposition was applied to suppress the clutter signal in the flow phantom. The BSC was calculated using the reference phantom method, and it was parametrized by spectral slope and mid-band fit (MBF) between 4–12 MHz. The velocity distribution was estimated by the block matching method, and the shear rate was estimated by the least squares approximation of the slope near the wall. Consequently, the spectral slope of the saline sample was always around four (Rayleigh scattering), independently of the shear rate, because the RBCs did not aggregate in the solution. Conversely, the spectral slope of the plasma sample was lower than four at low shear rates but approached four by increasing the shear rate, because the aggregations were presumably dissolved by the high shear rate. Moreover, the MBF of the plasma sample decreased from −36 to −49 dB in both flow phantoms with increasing shear rates, from approximately 10 to 100 s−1. The variation in the spectral slope and MBF in the saline sample was comparable to the results of in vivo cases in healthy human jugular veins when the tissue and blood flow signals could be separated.

Gamma-ray flares of blazars may be accompanied by high-energy neutrinos due to interactions of high-energy cosmic rays in the jet with photons, as suggested by the detection of the high-energy neutrino IceCube-170922A during a major gamma-ray flare from blazar TXS 0506+056 at the ∼3 σ significance level. In this work, we present a statistical study of gamma-ray emission from blazars to constrain the contribution of gamma-ray flares to their neutrino output. We construct weekly binned light curves for 145 gamma-ray bright blazars in the Fermi Large Area Telescope Monitored Source List adding TXS 0506+056. We derive the fraction of time spent in the flaring state (flare duty cycle) and the fraction of energy released during each flare from the light curves with a Bayesian blocks algorithm. We find that blazars with lower flare duty cycles and energy fractions are more numerous among our sample. We identify a significant difference in flare duty cycles between blazar subclasses at a significance level of 5%. Then using a general scaling relation for the neutrino and gamma-ray luminosities, ${L}_{\nu }\propto {({L}_{\gamma })}^{\gamma }$ with a weighting exponent of γ = 1.0–2.0, normalized to the quiescent gamma-ray or X-ray flux of each blazar, we evaluate the neutrino energy flux of each gamma-ray flare. The gamma-ray flare distribution indicates that blazar neutrino emission may be dominated by flares for γ ≳ 1.5. The neutrino energy fluxes for 1 week and 10 yr bins are compared with the decl.-dependent IceCube sensitivity to constrain the standard neutrino emission models for gamma-ray flares. Finally, we present the upper-limit contribution of blazar gamma-ray flares to the isotropic diffuse neutrino flux.

A long noncoding RNA, nuclear paraspeckle assembly transcript 1 (NEAT1) variant 1 (NEAT1v1), confers radioresistance to hepatocellular carcinoma (HCC) cells by inducing autophagy via γ-aminobutyric acid A receptor-associated protein (GABARAP). Radiation induces oxidative stress to damage cellular components and organelles, but it remains unclear how NEAT1v1 protects HCC cells from radiation-induced oxidative stress via autophagy. To address this, we precisely investigated NEAT1v1-induced autophagy in irradiated HCC cell lines. X-ray irradiation significantly increased cellular and mitochondrial oxidative stress and mitochondrial DNA content in HCC cells while NEAT1v1 suppressed them. NEAT1v1 concomitantly induced the phosphatase and tensin homolog-induced kinase 1 (PINK1)/parkin-mediated mitophagy. Interestingly, parkin expression was constitutively upregulated in NEAT1v1-overexpressing HCC cells, leading to increased mitochondrial parkin levels. Superoxide dismutase 2 (SOD2) was also upregulated by NEAT1v1, and GABARAP or SOD2 knockdown in NEAT1v1-overexpressing cells increased mitochondrial oxidative stress and mitochondrial DNA content after irradiation. Moreover, it was suggested that SOD2 was involved in NEAT1v1-induced parkin expression, and that GABARAP promoted parkin degradation via mitophagy. This study highlights the unprecedented roles of NEAT1v1 in connecting radioresistance and mitophagy in HCC.

Purpose: Surgical spacer placement (SSP) is useful in particle therapy (PT) for patients with abdominal or pelvic tumors located adjacent to normal organs. We developed a nonwoven fabric bioabsorbable spacer made of polyglycolic acid (PGA) sutures that degrades via hydrolysis. We then conducted this first-in-human phase 1 study of the combination of SSP and PT using the PGA spacer, which we termed space-making PT (SMPT). This study aimed to evaluate the safety and efficacy of SMPT in patients with unresectable malignant tumor located adjacent to normal organs. Methods and Materials: The eligibility criteria included histologically proven malignant abdominal or pelvic tumor adjacent to the intestines, no metastasis, and no previous radiation therapy. Periodic computed tomography (CT) images were obtained before SSP and before, during, and after PT until the spacer disappeared. Treatment planning was performed for each CT image set until the end of PT, and doses for the planning target volume and organs at risk were analyzed. The thickness and volume of the PGA spacer were measured in each CT image set. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0. Results: Five patients were enrolled in this study. All patients received 70.4 Gy (relative biological effectiveness) of irradiation. V95% of the planning target volume before SSP, at the beginning of PT, and at the end of PT was 82.1% ± 11.3%, 98.1% ± 1.1%, and 97.1% ± 0.8%, respectively. The PGA spacers maintained enough thickness (≥1 cm) until the end of PT and disappeared within 8 months after SSP in all patients. No grade ≥3 acute adverse events were observed. Conclusions: The SMPT is feasible and useful for abdominal or pelvic tumors adjacent to the intestines. This method may be applicable to unresectable tumors located adjacent to normal organs and may expand the indications of PT.

Some bone lesions are reported to mimic bone metastasis on imaging tests. Herein, we report a case of a 55-year-old Japanese man who presented with a skin tumor on the left lower extremity. He also had a history of recurrent generalized cutaneous blister and erosion formation since childhood. His skin lesions were diagnosed as cutaneous squamous cell carcinoma complicated by recessive dystrophic epidermolysis bullosa. Magnetic resonance imaging of the left lower extremity detected multiple focal bone lesions mimicking bone metastases in the left femur and tibia. However, bone biopsy revealed that the bone lesions were osteonecrosis without tumor cells. We suggest that cancer-induced osteonecrosis should be included in the differential diagnosis of bone lesions suspected of being metastases on magnetic resonance imaging.

Purpose: Effective methods to ameliorate radiation enteropathy have not been developed. To address this issue, we investigated the reduced form of coenzyme Q10 (rCoQ10) as a potential radioprotector in a mouse model. Methods and Materials: rCoQ10 was added to a standard laboratory mouse diet at a final concentration of 1.0% 9 days before irradiation and 30 days thereafter or dissolved in corn oil and administered transorally. Accumulated amounts of coenzyme Q10 (CoQ10) or coenzyme Q9 in the intestine were measured by high-performance liquid chromatography. Reactive oxygen species (ROS), apoptosis, and morphologic changes in the intestine were assessed by immunohistochemistry after administration of 13 Gy of x-ray to the mouse abdomen. Body weight and survival were monitored for 30 days after irradiation. Cytotoxicity using 3 human cancer cell lines and the tumor growth–inhibiting effect in a xenograft were investigated to determine whether rCoQ10 interferes with radiation-specific cytotoxic effects on tumor growth. Results: CoQ10 was greatly accumulated in all sections of the intestine after both massive transoral dosing and dietary administration, whereas coenzyme Q9 was not. Administration of rCoQ10 suppressed ROS production and inhibited apoptosis in the crypts, resulting in preservation of villi structures after irradiation. Notably, 92% of mice fed the rCoQ10-supplemented diet were healthy and alive 30 days after irradiation, whereas 50% of control mice died (P

Gastrointestinal toxicity is frequently observed secondary to accidental or therapeutic radiation exposure. However, the variation in the intestinal metabolites after abdominal radiation exposure remains ambiguous. In the present study, C57BL/6 mice were exposed to 0, 2, and 20 Gy irradiation dose. The Head and chest of each mouse were covered with a lead shield before x-ray irradiation. 24 h post-irradiation treatment, intestinal tissue of each mouse was excised and prepared for metabolites measurement using gas chromatography-mass spectrometry (GC-MS). Our comprehensive analysis of metabolites in the intestinal tissues detected 44 metabolites after irradiation, including amino acids, carbohydrates, organic acids, and sugars. Amino acid levels in the intestinal tissue gradually rose, dependent on the radiation dose, perhaps as an indication of oxidative stress. Our findings raise the possibility that amino acid metabolism may be a potential target for the development of treatments to alleviate or mitigate the harmful effects of oxidative stress-related gastrointestinal toxicity due to radiation exposure.

A long noncoding RNA (lncRNA), nuclear enriched abundant transcript 1 (NEAT1) variant 1 (NEAT1v1), is involved in the maintenance of cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). CSCs are suggested to play important roles in therapeutic resistance. Therefore, we investigated whether NEAT1v1 is involved in the sensitivity to radiation therapy in HCC. Gene knockdown was performed using short hairpin RNAs, and NEAT1v1-overexpressing HCC cell lines were generated by stable transfection with a NEAT1v1-expressing plasmid DNA. Cells were irradiated using an X-ray generator. We found that NEAT1 knockdown enhanced the radiosensitivity of HCC cell lines and concomitantly inhibited autophagy. NEAT1v1 overexpression enhanced autophagy in the irradiated cells and conferred radioresistance. Gamma-aminobutyric acid receptor-associated protein (GABARAP) expression was downregulated by NEAT1 knockdown, whereas it was upregulated in NEAT1v1-overexpressing cells. Moreover, GABARAP was required for NEAT1v1-induced autophagy and radioresistance as its knockdown significantly inhibited autophagy and sensitized the cells to radiation. Since GABARAP is a crucial protein for the autophagosome-lysosome fusion, our results suggest that NEAT1v1 confers radioresistance to HCC by promoting autophagy through GABARAP.

Introduction: Revascularization surgery for adult moyamoya disease (MMD) with ischemic presentation changes cognitive function and prevents further cerebral ischemic events. Most studies, however, repeated neuropsychological evaluation within 1 year after surgery. Our previous prospective cohort study of adult patients with MMD with misery perfusion who underwent direct revascularization surgery showed cognitive improvement and decline in 31% and 44%, respectively, of the patients 2 months after surgery. The present prospective study aimed to elucidate the 5-year cognitive changes after direct revascularization surgery in adult patients with cerebral misery perfusion due to ischemic MMD by following the same patients. Methods: In total, 31 patients were prospectively followed up for 5 years after direct revascularization surgery. Five types of neuropsychological tests were performed preoperatively, 2 months after surgery, and at the end of the 5-year follow-up. Cerebral blood flow in the symptomatic cerebral hemisphere relative to that in the ipsilateral cerebellar hemisphere (hemispheric RCBF) was measured using brain perfusion single-photon emission computed tomography preoperatively and at the end of the 5-year follow-up. Results: Based on results of pre- and postoperative neuropsychological tests, 11, 10, and 10 patients showed cognitive improvement, no change in cognitive function, and cognitive decline, respectively, at the end of the 5-year follow-up. These ratios were not significantly different compared with those 2 months after surgery (cognitive improvement, no change in cognitive function, and cognitive decline in 10, eight, and 13 patients, respectively). Although hemispheric RCBF was significantly greater at the end of the 5-year follow-up than before surgery in patients with cognitive improvement (80.7 ± 6.1% versus 92.9 ± 5.5%; p = 0.0033) and in those showing no change in cognitive function (85.6 ± 3.5 versus 91.5 ± 5.2%; p = 0.0093), this value was significantly lower at the end of the 5-year follow-up than before surgery in patients with cognitive decline (83.8 ± 3.7 versus 81.0 ± 5.8%; p = 0.0367). Conclusion: One-third of adult patients with cerebral misery perfusion due to ischemic MMD who underwent direct revascularization surgery exhibited cognitive improvement, and one-third exhibited decline at the end of the 5-year follow-up. The former and latter patients had increased and decreased CBF, respectively, in the affected cerebral hemisphere at the end of the 5-year follow-up compared with preoperative brain perfusion.

Objective Numerous studies have examined whether school smoking prevention education for minors can reduce smoking rates in later life, but no consensus has been established. Doctors in Kanazawa, Japan, voluntarily visited elementary schools to provide smoking prevention education for 12-year-old students. We attempted to assess whether this education is effective for lowering smoking rates in students when they reach 20 years of age. Methods We defined a community area that has 14 elementary schools for this study. We provided education at some of the 14 schools once a year for 12-year-old students. After 8 years, we carried out a questionnaire survey on smoking for 20-year-old young adults. We compared smoking behaviors at the age of 20 between the educated and the control groups of the 3 year period from 2015. Results The smoking rate was significantly lower in the educated group, indicating that smoking prevention education in elementary schools for 12-year-old students, provided by doctors, reduced smoking behavior, even at the age of 20. Conclusions Smoking prevention education for 12-year-old students at elementary schools by volunteer physicians significantly reduced smoking rate at the age of 20. Funding statement: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. There are no conflicts of interest by any author.

We previously constructed a risk prediction model of vancomycin (VCM)-associated nephrotoxicity for use when performing initial therapeutic drug monitoring (TDM), using decision tree analysis. However, we could not build a model to be used at the time of initial administration due to insufficient sample size. Therefore, we performed a multicenter study at four hospitals in Japan. We investigated patients who received VCM intravenously at a standard dose from the first day until the initial TDM from November 2011 to March 2019. Acute kidney injury (AKI) was defined according to the criteria established by the “Kidney disease: Improving global outcomes” group. We extracted potential risk factors that could be evaluated on the day of initial administration and constructed a flowchart using a chi-squared automatic interaction detection algorithm. Among 843 patients, 115 (13.6%) developed AKI. The flowchart comprised three splitting variables (concomitant drugs (vasopressor drugs and tazobactam/piperacillin) and body mass index ≥ 30) and four subgroups. The incidence rates of AKI ranged from 9.34 to 36.8%, and they were classified as low-, intermediate-, and high-risk groups. The accuracy of flowchart was judged appropriate (86.4%). We successfully constructed a simple flowchart predicting VCM-induced AKI to be used when starting VCM administration.

The purpose of the present study was to determine whether objective gait test scores obtained using a tri-axial accelerometer can detect subjective improvement in gait as determined by the patient after carotid endarterectomy (CEA). Each patient undergoing CEA for ipsilateral internal carotid artery stenosis determined whether their gait was subjectively improved at six months after CEA when compared with preoperatively. Gait testing using a tri-axial accelerometer was also performed preoperatively and six months postoperatively. Twelve (15%) of 79 patients reported subjectively improved gait. Areas under the receiver operating characteristic curve for differences between pre- and postoperative test values in stride time, cadence, and ground floor reaction for detecting subjectively improved gait were 0.995 (95% confidence interval (CI), 0.945–1.000), 0.958 (95%CI, 0.887–0.990), and 0.851 (95%CI, 0.753–0.921), respectively. Cut-off points for value differences in detecting subjectively improved gait were identical to mean −1.7 standard deviation (SD) for stride time, mean +1.6 SD for cadence, and mean +0.4 SD for ground floor reaction of control values from normal subjects. Objective gait test scores obtained using the tri-axial accelerometer can detect subjective gait improvements after CEA. When determining significant postoperative improvements in gait using a tri-axial accelerometer, optimal cut-off points for each test value can be defined.

The development of potentially safe radiosensitizing agents is essential to enhance the treatment outcomes of radioresistant cancers. The titanium peroxide nanoparticle (TiOxNP) was originally produced using the titanium dioxide nanoparticle, and it showed excellent reactive oxygen species (ROS) generation in response to ionizing radiation. Surface coating the TiOxNPs with polyacrylic acid (PAA) showed low toxicity to the living body and excellent radiosensitizing effect on cancer cells. Herein, we evaluated the mechanism of radiosensitization by PAA-TiOxNPs in comparison with gold nanoparticles (AuNPs) which represent high-atomic-number nanoparticles that show a radiosensitizing effect through the emission of secondary electrons. The anticancer effects of both nanoparticles were compared by induction of apoptosis, colony-forming assay, and the inhibition of tumor growth. PAA-TiOxNPs showed a significantly more radiosensitizing effect than that of AuNPs. A comparison of the types and amounts of ROS generated showed that hydrogen peroxide generation by PAA-TiOxNPs was the major factor that contributed to the nanoparticle radiosensitization. Importantly, PAA-TiOxNPs were generally nontoxic to healthy mice and caused no histological abnormalities in the liver, kidney, lung, and heart tissues.

Measurements of the interfacial area concentration and the void fraction in a vertical upward air-water two-phase flow downward of single horizontal tube and horizontal tube bundle were carried out by a double sensor electrical conductivity probe. The test section comprised a 50mm × 50mm square channel partially obstructed by the single horizontal tube and the horizontal tube bundle inside. Five types of the test sections which the horizontal tube arrangement is different were used to provide various distributions of air-water two-phase flow downstream of the test section. The superficial gas velocity and superficial liquid velocity ranged from 0.02 to 0.20 m/s and from 0.13 to 0.53 m/s, respectively. Local flow measurements were performed at the three axial locations of z (z') = 110 (70), 340 (300), and 640 (600) mm and the transverse locations from r = 3 to 25 mm. The single horizontal tube and the horizontal tube bundle effect the distributions of the interfacial area concentration and the void fraction at z (z') = 110 (70). This effect was decreased along the flow direction due to the diffusion of bubble toward horizontal direction. At high gas flow rate conditions, void fraction increase, while interfacial area concentration decrease with increasing gas flow rate because of the bubble coalescence.

In the present investigation, detailed observation on the pressure drop characteristics affected by the wall wettability in a curved mini-channel were carried out. The test channel is the serpentine channel with six straight sections and curved sections. The test channel has a square cross section that has 2.0mm on each side, and the radius of curvature was 1.0mm. The test channel was made of the transparent acrylic resin for flow visualization. In order to investigate the influence of the wall wettability, water-repellent and attracting treatments were applied to the acrylic channel, respectively. In this investigation, in relation to the analysis method of the pressure drop, we evaluated the time averaged pressure drop and the pressure fluctuation, respectively. In the case of the water-repellent and attracting channel, the time averaged pressure drop was lower than the normal channel. In addition, in the straight section without the water repellent, the fluctuation of the pressure drop was considered to be correlated only by the Lockhart-Martinelli's parameter. On the other hand, in the cases the effects of channel curvature and water repellent are outstanding, the fluctuation of the pressured drop was widely scattered and hard to be correlated by the Lockhart-Martinelli's parameter.

Measurement and numerical simulation of the interfacial area concentration and the void fraction were carried out to develop transport equation of interfacial area concentration to fulfill the requirements of an improved prediction accuracy of gas-liquid two-phase flow behavior. Measurements in a vertical upward air-water two-phase flow were conducted at the conditions of ambient temperature and atmospheric pressure. Test section was a round tube of 50 mm in inside diameter. The superficial gas velocity and the superficial liquid velocity ranged from 0.02 to 0.12 m/s and from 0.17 to 0.85 m/s, respectively. Two types of bubble generator were used in this study. One is that air was injected from the wall of the flow channel to the water (wall injection type). The other one is that air was injected from the pipe located at the center of the flow channel (pipe injection type). Measurements of the void fraction and the interfacial area concentration were performed using double sensor electrical resistivity probe at five axial locations of z = 45, 275, 575, 805, and 2365 mm for the wall injection type of bubble generator and z = 110, 410, 640, 1170, and 2230 mm for the pipe injection type of bubble generator, and transverse locations from r = 0 to 23 mm. In the numerical simulation, a transport equation of interfacial area concentration was developed in the previous study. This equation is validated by the previous and present experimental data. Consequently, good agreement is obtained between these results.

We report a case of IgG4-related disease (IgG4-RD) with multiple ten-organ involvement. This case showed many clinical findings, such as bilateral swelling of salivary and lacrimal glands, autoimmune pancreatitis, interstitial nephritis, retroperitoneal fibrosis, periaortitis, systemic swelling of lymph nodes, pulmonary lesions, splenomegaly, and jejunal lesions. He was suspected as having SLE or malignant lymphoma but diagnosed as having IgG4-RD by the elevated serum IgG4 level and histological findings from kidney and lymph node. We report a case of IgG4-RD with multiple ten-organ involvement that was successfully treated with prednisolone therapy.

Non-coding small RNAs are involved in many physiological responses including viral life cycles. Adenovirus-encoding small RNAs, known as virus-associated RNAs (VA RNAs), are transcribed throughout the replication process in the host cells, and their transcript levels depend on the copy numbers of the viral genome. Therefore, VA RNAs are abundant in infected cells after genome replication, i.e. during the late phase of viral infection. Their function during the late phase is the inhibition of interferon-inducible protein kinase R (PKR) activity to prevent antiviral responses; recently, mivaRNAs, the microRNAs processed from VA RNAs, have been reported to inhibit cellular gene expression. Although VA RNA transcription starts during the early phase, little is known about its function. The reason may be because much smaller amount of VA RNAs are transcribed during the early phase than the late phase. In this study, we applied replication-deficient adenovirus vectors (AdVs) and novel AdVs lacking VA RNA genes to analyze the expression changes in cellular genes mediated by VA RNAs using microarray analysis. AdVs are suitable to examine the function of VA RNAs during the early phase, since they constitutively express VA RNAs but do not replicate except in 293 cells. We found that the expression level of hepatoma-derived growth factor (HDGF) significantly decreased in response to the VA RNAs under replication-deficient condition, and this suppression was also observed during the early phase under replication-competent conditions. The suppression was independent of mivaRNA-induced downregulation, suggesting that the function of VA RNAs during the early phase differs from that during the late phase. Notably, overexpression of HDGF inhibited AdV growth. This is the first report to show the function, in part, of VA RNAs during the early phase that may be contribute to efficient viral growth.

BACKGROUND AND PURPOSE: To investigate the prognostic value of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with laryngeal cancer. MATERIALS AND METHODS: The study included 51 patients of whom 30 underwent definitive radiotherapy with or without chemotherapy and 21 underwent radical surgery with or without adjuvant chemoradiation therapy. FDG uptake by both the primary lesion and the neck node was measured using the maximum standardized uptake value (SUVmax). The effects of clinicopathological factors including primary tumor SUVmax and nodal SUVmax on progression-free survival, local control, nodal progression-free survival, and distant metastasis-free survival were evaluated using the log-rank test and Cox method. RESULTS: The median duration of follow-up was 48.6 months (range 8 to 82.1 months). Univariate analysis showed that nodal SUVmax, N status, and tumor TNM stage were significantly associated with recurrence, whereas primary tumor SUVmax, age, treatment strategy and T status were not. Multivariate analysis demonstrated that only the nodal SUVmax was a significantly unfavorable factor for progression-free survival (p = 0.029, hazard ratio 0.54, 95% CI 0.38-0.87) and nodal progression-free survival (p = 0.023, hazard ratio 0.51, 95% CI 0.34-0.81). ROC curve analysis and log-rank test showed that patients with a high nodal SUVmax (≧ 4) had a significantly lower progression-free survival rate than those with a low SUVmax (

Around the fifth week after birth, the vaginal cavity in female mouse pups opens to the overlaying skin. This postnatal tissue remodeling of the genital tract occurs during puberty, and it largely depends upon hormonally induced apoptosis that mainly occurs in the epithelium at the lower part of the mouse vaginal cavity. Previously, we showed that most BALB/c mice lacking the class IV Semaphorin (Sema4D) develop imperforate vagina and hydrometrocolpos; therefore, we reasoned that the absence of Sema4D-induced apoptosis in vaginal epithelial cells may cause the imperforate vagina. Sema4D signals via the Plexin-B1 receptor; nevertheless detailed mechanisms mediating this hormonally triggered apoptosis are not fully documented. To investigate the estrogen-dependent control of Sema4D signaling during the apoptosis responsible for mouse vaginal opening, we examined structural and functional modulation of Sema4D, Plexin-B1, and signaling molecules by analyzing both wild-type and Sema4D-/- mice with or without ovariectomy. Both the release of soluble Sema4D and the conversion of Plexin-B1 by proteolytic processing in vaginal tissue peaked 5 weeks after birth of wild-type BALB/c mice at the time of vaginal opening. Estrogen supplementation of ovariectomized wild-type mice revealed that both the release of soluble Sema4D and the conversion of Plexin-B1 into an active form were estrogen-dependent and concordant with apoptosis. Estrogen supplementation of ovariectomized Sema4D-/- mice did not induce massive vaginal apoptosis in 5-week-old mice; therefore, Sema4D may be an essential apoptosis-inducing ligand that acts downstream of estrogen action in vaginal epithelium during this postnatal tissue remodeling. Analysis of ovariectomized mice also indicated that Sema4D contributed to estrogen-dependent dephosphorylation of Akt and ERK at the time of vaginal opening. Based on our results, we propose that apoptosis in vaginal epithelium during postnatal vaginal opening is induced by enhanced Sema4D signaling that is caused by estrogen-dependent structural changes of Sema4D and Plexin-B1.

The aim of the present study was to determine whether preoperative three-dimensional (3D) fast spin-echo (FSE) T1-weighted magnetic resonance (MR) plaque imaging for severely stenotic cervical carotid arteries could accurately predict the development of artery-to-artery emboli during exposure of the carotid arteries in carotid endarterectomy (CEA). Seventy-five patients underwent preoperative MR plaque imaging and CEA under transcranial Doppler ultrasonography of the ipsilateral middle cerebral artery. On reformatted axial MR image slices showing the maximum plaque occupation rate (POR) and maximum plaque intensity for each patient, the contrast ratio (CR) was calculated by dividing the internal carotid artery plaque signal intensity by the sternocleidomastoid muscle signal intensity. For all patients, the area under the receiver operating characteristic curve (AUC)—used to discriminate between the presence and absence of microembolic signals—was significantly greater for the CR on the axial image with maximum plaque intensity (CRmax intensity) (0.941) than for that with the maximum POR (0.885) (p < 0.05). For 32 patients in whom both the maximum POR and the maximum plaque density were identified, the AUCs for the CR were 1.000. Preoperative 3D FSE T1-weighted MR plaque imaging accurately predicts the development of artery-to-artery emboli during exposure of the carotid arteries in CEA.

The purpose of the present study was to determine whether cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during exposure of the carotid arteries in carotid endarterectomy (CEA). In patients undergoing CEA for internal carotid artery stenosis (≥70%), cerebral blood flow (CBF) was measured using single-photon emission computed tomography (SPECT) before and immediately after CEA. Microembolic signals (MES) were identified using transcranial Doppler during carotid exposure. Diffusion-weighted magnetic resonance imaging (DWI) was performed within 24 h after surgery. Of 32 patients with a combination of reduced cerebrovascular reactivity to acetazolamide on preoperative brain perfusion SPECT and MES during carotid exposure, 14 (44%) showed cerebral hyperperfusion (defined as postoperative CBF increase ≥100% compared with preoperative values), and 16 (50%) developed DWI-characterized postoperative cerebral ischemic lesions. Postoperative cerebral hyperperfusion was significantly associated with the absence of DWI-characterized postoperative cerebral ischemic lesions (95% confidence interval, 0.001–0.179; p = 0.0009). These data suggest that cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during carotid exposure in CEA, supporting the “impaired clearance of emboli” concept. Blood pressure elevation following carotid declamping would be effective when embolism not accompanied by cerebral hyperperfusion occurs during CEA.

BACKGROUND: Peripheral nerve damage of the cornea is a complication following surgery or infection which may lead to decreased visual function. We examined the efficacy of the semaphorin 3A inhibitor, SM-345431, in promoting regeneration of peripheral nerves in a mouse corneal transplantation model. METHODOLOGY/PRINCIPAL FINDINGS: P0-Cre/Floxed-EGFP mice which express EGFP in peripheral nerves cells were used as recipients of corneal transplantation with syngeneic wild-type mouse cornea donors. SM-345431 was administered subconjunctivally every 2 days while control mice received vehicle only. Mice were followed for 3 weeks and the length of regenerating nerves was measured by EGFP fluorescence and immunohistochemistry against βIII tubulin. Cornea sensitivity was also measured by the Cochet-Bonnet esthesiometer. CD31 staining was used to determine corneal neovascularization as a possible side effect of SM-345431. Regeneration of βIII tubulin positive peripheral nerves was significantly higher in SM-345431 treated mice compared to control. Furthermore, corneal sensitivity significantly improved in the SM-345431 group by 3 weeks after transplantation. Neovascularization was limited to the peripheral cornea with no difference between SM-345431 group and control. CONCLUSIONS/SIGNIFICANCE: Subconjunctival injections of SM-345431 promoted a robust network of regenerating nerves as well as functional recovery of corneal sensation in a mouse keratoplasty model, suggesting a novel therapeutic strategy for treating neurotrophic corneal disease.

ABSTRACT Purpose: To investigate a method to determine the appropriate length of ureteral stents, given that the stent length may lead to exacerbation of urinary symptoms if the stent crosses the bladder midline. Materials and Methods: We retrospectively reviewed the position of the distal curl of the ureteral stent using kidney/ureter/bladder (KUB) radiographs after ureteroscopic lithotripsy in 165 patients who underwent placement of 24- or 26-cm ureteral stents. According to the KUB findings, we categorized the position of the distal curl of the ureteral stent into two groups. In Group 1, the stents did not cross the midline (appropriate length); in Group 2, the stents crossed the midline (inappropriate length). We assessed several patient parameters (sex, height, body mass index, and stone side) and the index of ureteral length using KUB radiographs (“C-P”) and computed tomography (CT, “P-V”). Multivariate analysis was performed to identify the most significant factors affecting the position of ureteral stents. We also calculated the cutoff points of the receiver operating characteristic (ROC) curve of C-P and P-V for the position of ureteral stents. Results: The multivariate analysis showed that C-P was the most significant factor affecting the position of ureteral stents (p < 0.001) in patients with 24- and 26-cm ureteral stents. Comparison of the ROC curves of C-P and P-V showed that C-P was superior to P-V (p < 0.01) in patients with 24- and 26-cm stents. Conclusion: The use of KUB radiographs was effective and simple in determining the appropriate length of ureteral stents.