Nitrogen-Containing Carbon Tubes Fabricated by Light Irradiation.

Cotton-core/polypyrrole (PPy)-sheath fibers (cotton/PPy fibers) were synthesized by aqueous chemical oxidative seeded polymerization and were utilized as precursors for nitrogen-containing carbon (NCC) tubes. Irradiation of the cotton/PPy fibers with a near-infrared (NIR) laser heated them to approximately 300 °C due to light-to-heat photothermal conversion by the PPy, and the cotton core was thermally decomposed and vaporized. Scanning electron microscopy studies revealed the formation of tubes with monodispersed diameters, and elemental microanalysis, Fourier transform infrared spectroscopy, and Raman spectroscopy confirmed that the PPy sheath was converted into NCC. Furthermore, sunlight also worked as the light source in fabricating the NCC tubes. The thicknesses of the tubes were controlled between 410 nm and 2.30 µm by tuning the PPy sheath thickness. The method developed in this study can be extended to other polymeric fibers, including acrylic and wool fibers. The shapes of the cross sections and surface nanomorphologies of the NCC tubes can be reflected in those of the polymer/PPy fibers.

Cerebellar ataxia-dominant phenotype in patients with ERCC4 mutations.

Autosomal recessive cerebellar ataxias (ARCAs) are clinically and genetically heterogeneous neurological disorders. Through whole-exome sequencing of Japanese ARCA patients, we identified three index patients from unrelated families who had biallelic mutations in ERCC4. ERCC4 mutations have been known to cause xeroderma pigmentosum complementation group F (XP-F), Cockayne syndrome, and Fanconi anemia phenotypes. All of the patients described here showed very slowly progressive cerebellar ataxia and cognitive decline with choreiform involuntary movement, with young adolescent or midlife onset. Brain MRI demonstrated atrophy that included the cerebellum and brainstem. Of note, cutaneous symptoms were very mild: there was normal to very mild pigmentation of exposed skin areas and/or an equivocal history of pathological sunburn. However, an unscheduled DNA synthesis assay of fibroblasts from the patient revealed impairment of nucleotide excision repair. A similar phenotype was very recently recognized through genetic analysis of Caucasian cerebellar ataxia patients. Our results confirm that biallelic ERCC4 mutations cause a cerebellar ataxia-dominant phenotype with mild cutaneous symptoms, possibly accounting for a high proportion of the genetic causes of ARCA in Japan, where XP-F is prevalent.

Adherence and feasibility of 2 treatment schedules of S-1 as adjuvant chemotherapy for patients with completely resected advanced lung cancer: a multicenter randomized controlled trial.

BACKGROUND: We conducted a multicenter randomized study of adjuvant S-1 administration schedules for surgically treated pathological stage IB-IIIA non-small cell lung cancer patients. METHODS: Patients receiving curative surgical resection were centrally randomized to arm A (4 weeks of oral S-1 and a 2-week rest over 12 months) or arm B (2 weeks of S-1 and a 1-week rest over 12 months). The primary endpoints were completion of the scheduled adjuvant chemotherapy over 12 months, and the secondary endpoints were relative total administration dose, toxicity, and 3-year disease-free survival. RESULTS: From April 2005 to January 2012, 80 patients were enrolled, of whom 78 patients were eligible and assessable. The planned S-1 administration over 12 months was accomplished to 28 patients in 38 arm A patients (73.7%) and to 18 patients in 40 arm B patients (45.0%, p = 0.01). The average relative dose intensity was 77.2% for arm A and 58.4% for arm B (p = 0.01). Drug-related grade 3 adverse events were recorded for 11% of arm A and 5% of arm B (p = 0.43). Grade 1-3 elevation of bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine transaminase were more frequently recorded in arm A than in arm B. The 3-year disease-free survival rate was 79.0% for arm A and 79.3% for arm B (p = 0.94). CONCLUSIONS: The superiority of feasibility of the shorter schedule was not recognized in the present study. The conventional schedule showed higher completion rates over 12 months (p = 0.01) and relative dose intensity of S-1 (p = 0.01). Toxicity showed no significant difference among the shorter schedule and the conventional schedule, except for grade 1-3 elevation of bilirubin. TRIAL REGISTRATION: This randomized multicenter study was retrospectively registered with the UMIN-CTR (UMIN000016086, registration date December 30, 2014).

Nipbl and mediator cooperatively regulate gene expression to control limb development.

Haploinsufficiency for Nipbl, a cohesin loading protein, causes Cornelia de Lange Syndrome (CdLS), the most common "cohesinopathy". It has been proposed that the effects of Nipbl-haploinsufficiency result from disruption of long-range communication between DNA elements. Here we use zebrafish and mouse models of CdLS to examine how transcriptional changes caused by Nipbl deficiency give rise to limb defects, a common condition in individuals with CdLS. In the zebrafish pectoral fin (forelimb), knockdown of Nipbl expression led to size reductions and patterning defects that were preceded by dysregulated expression of key early limb development genes, including fgfs, shha, hand2 and multiple hox genes. In limb buds of Nipbl-haploinsufficient mice, transcriptome analysis revealed many similar gene expression changes, as well as altered expression of additional classes of genes that play roles in limb development. In both species, the pattern of dysregulation of hox-gene expression depended on genomic location within the Hox clusters. In view of studies suggesting that Nipbl colocalizes with the mediator complex, which facilitates enhancer-promoter communication, we also examined zebrafish deficient for the Med12 Mediator subunit, and found they resembled Nipbl-deficient fish in both morphology and gene expression. Moreover, combined partial reduction of both Nipbl and Med12 had a strongly synergistic effect, consistent with both molecules acting in a common pathway. In addition, three-dimensional fluorescent in situ hybridization revealed that Nipbl and Med12 are required to bring regions containing long-range enhancers into close proximity with the zebrafish hoxda cluster. These data demonstrate a crucial role for Nipbl in limb development, and support the view that its actions on multiple gene pathways result from its influence, together with Mediator, on regulation of long-range chromosomal interactions.

[A Surgical Case of Intrapulmonary Bronchogenic Cyst Treated by Left Lower Lobectomy for Hemopneumothorax and Repeated Hemoptysis].

A 79-year-old female visited a hospital because of high fever and computed tomography(CT)showed a cystic lesion with fluid accumulation in her left lung. She had hemoptysis and left chest pain 3 days after antibiotic therapy was started. Chest CT demonstrated the cystic lesion rupturing and causing hemopneumothorax. Then she was referred to our department and thoracic drainage was performed. However, a week after the drainage, she had hemoptysis and chest pain again, and the left lower lobectomy was performed. Histopathological findings showed the cystic lesion was intrapulmonary bronchogenic cyst. We describe a rare case of the hemopneumothorax due to the hemorrhage in the bronchogenic cyst.

Physiological and pathological relevance of secretory microRNAs and a perspective on their clinical application.

MicroRNAs (miRNAs) have attracted significant attention because of their important roles in a variety of physiological and pathological processes. Recent studies have shown that many cell types secrete miRNAs by packaging them into lipid-bilayered small vesicles called exosomes. Furthermore, exosomal miRNAs travel between cells, exert their RNAi effects in the recipient cells, and play important roles in various biological processes. In this article, we will summarize and describe the latest studies on exosomal miRNAs by focusing on their roles in cancer progression, immune regulation, and tissue repair. We will also provide a perspective on the clinical applications of this research field.

Hemichorea in a thymoma patient without anti-CRMP-5 antibody.

We reported a 72-year-old man with thymoma who presented with hemichorea. Although his brain CT and MRI revealed no abnormality, regional cerebral blood flow changes, identified by single photon emission computed tomography, suggested that the mechanism underlying the chorea seemed to be a dysfunction of the subthalamic nucleus and pallidum. His hemichorea was completely resolved after thymectomy. Absence of serum anti-neural autoantibodies, including small-cell lung carcinoma-related chorea anti-CRMP-5 antibody, suggests that mechanisms different from cross-talk neural-targeted tumor immune response can be responsible for the thymoma-associated paraneoplastic chorea.

Schwannoma diagnosed by endobronchial ultrasound-guided intranodal forceps biopsy using standard-sized biopsy forceps: A case report.

Schwannomas are classified as neurogenic tumors and are the most frequent nerve sheath tumors in the paravertebral mediastinum. Recently, the addition of endobronchial ultrasound-guided intranodal forceps biopsy (EBUS-IFB) using standard-sized biopsy forceps (SBFs) to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for metastatic lymph nodes in lung cancer patients reportedly improved the quality and quantity of the obtained specimens without significant complications. However, reports on the usefulness of this technique for benign diseases remain scarce. Here we report a case of schwannoma in the middle mediastinum, which was diagnosed by EBUS-IFB using SBFs, despite inadequate specimens obtained via EBUS-TBNA. An 80-year-old woman presented with dyspnea and a 5-cm sized middle mediastinal tumor. EBUS-TBNA and EBUS-IFB using SBFs were performed for histological diagnosis. No complications were associated with the bronchoscopy procedure, and schwannoma was solely diagnosed using the EBUS-IFB specimens. EBUS-IFB using SBFs is potentially useful for diagnosing benign diseases, including schwannomas, which are often difficult to diagnose with EBUS-TBNA.

Influence of background cardiovascular risk factors on VEGF inhibitor-related adverse vascular events in patients with non-small cell lung cancer: a retrospective study.

PURPOSE: Vascular endothelial growth factor (VEGF) inhibitors are widely used in chemotherapy for non-small lung cancer (NSCLC). The purpose of the current study was to examine the impact of background cardiovascular risk factors on VEGF inhibitor-related adverse vascular events (VEGF-related AVEs) in patients with NSCLC who also had comorbidities. METHODS: We conducted a retrospective study of 118 NSCLC patients treated with bevacizumab or ramucirumab from April 2010 to December 2022. We compared baseline cardiovascular risk factors with VEGF-related AVEs. RESULTS: VEGF-related AVEs and discontinuation due to VEGF-related AVEs were reported in 54 patients and 21 patients, respectively. VEGF-related AVEs were significantly more common with male sex, smoking history, history of hypertension, dyslipidemia, diabetes mellitus, or cardiovascular disease. Discontinuation due to VEGF-related AVEs was significantly more common in patients with history of hypertension or chronic kidney disease. VEGF-related AVEs were significantly more common in patients with ≥ 3 cardiovascular risk factors than patients with < 3. Discontinuation due to VEGF-related AVEs was significantly more common in patients with ≥ 4 cardiovascular risk factors than patients with < 4. Multivariate analysis demonstrated that male sex, hypertension, and ≥ 6 cycles of VEGF inhibitors were each associated with VEGF-related AVEs and hypertension was associated with discontinuation due to VEGF-related AVEs. CONCLUSION: Our study demonstrated that history of hypertension was independently associated with increased risk of both VEGF-related AVEs and discontinuation due to VEGF-related AVEs. In conclusion, we need to be aware of VEGF-related AVEs when using VEGF inhibitors for patients with ≥ 3 cardiovascular risk factors.

SGTA associates with intracellular aggregates in neurodegenerative diseases.

Intracellular aggregates are a common pathological hallmark of neurodegenerative diseases such as polyglutamine (polyQ) diseases, amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple system atrophy (MSA). Aggregates are mainly formed by aberrant disease-specific proteins and are accompanied by accumulation of other aggregate-interacting proteins. Although aggregate-interacting proteins have been considered to modulate the formation of aggregates and to be involved in molecular mechanisms of disease progression, the components of aggregate-interacting proteins remain unknown. In this study, we showed that small glutamine-rich tetratricopeptide repeat-containing protein alfa (SGTA) is an aggregate-interacting protein in neurodegenerative diseases. Immunohistochemistry showed that SGTA interacted with intracellular aggregates in Huntington disease (HD) cell models and neurons of HD model mice. We also revealed that SGTA colocalized with intracellular aggregates in postmortem brains of patients with polyQ diseases including spinocerebellar ataxia (SCA)1, SCA2, SCA3, and dentatorubral-pallidoluysian atrophy. In addition, SGTA colocalized with glial cytoplasmic inclusions in the brains of MSA patients, whereas no accumulation of SGTA was observed in neurons of PD and ALS patients. In vitro study showed that SGTA bound to polyQ aggregates through its C-terminal domain and SGTA overexpression reduced intracellular aggregates. These results suggest that SGTA may play a role in the formation of aggregates and may act as potential modifier of molecular pathological mechanisms of polyQ diseases and MSA.

Mucinous adenocarcinoma of the thymus: a distinct variant of thymic carcinoma.

BACKGROUND: Primary thymic mucinous adenocarcinoma is a recently described subtype of thymic carcinoma, which behaves aggressively. METHODS: The authors analyzed the clinical and pathological findings of three cases of thymic mucinous adenocarcinoma, and reviewed five cases previously reported in the English literature. RESULTS: The patients were two males and one female between the ages of 38 and 55 years. Macroscopically, the tumors were mostly solid and white to yellowish-white. Areas with a gelatinous appearance were present. Histologically, all of the tumors were adenocarcinomas with abundant mucin production, which resembled the mucinous adenocarcinomas of other organs. Malignant tumor cells in nests, tubules and cribriform structures floated in pools of extracellular mucin. In one case, associated thymic cysts were found at the periphery of the tumor. The cyst wall was partially lined by malignant mucinous epithelium, which showed transition from benign thymic epithelium. Immunohistochemically, all of the tumors showed positive immunoreactivity for cytokeratin (CK) 20 and carcinoembryonic antigen (CEA). CD5 was diffusely positive in one case, and focally positive in the other two cases. The prognoses of these cases were extremely poor, and two of the patients died within 24 months. CONCLUSION: Growing evidence suggests that mucinous adenocarcinoma is a distinct morphological variant of primary thymic carcinoma. We believe that clinicians and surgical pathologists should include thymic mucinous adenocarcinoma in the differential diagnosis of mediastinal adenocarcinoma.

Preparation of Ni nanoparticles by liquid-phase reduction to fabricate metal nanoparticle-polyimide composite films.

Nickel-nanoparticle-containing polyimide composite films were prepared by liquid-phase reduction of Ni2+ ions with potassium borohydride (KBH4). The nanoparticles were amorphous with diameters of approximately 10-20 nm, depending on the KBH4 concentration and reduction temperature. At high KBH4 concentrations, the nanoparticles appeared to contain various nickel boride species. The number of nanoparticles and Ni content both increased upon repeated adsorption/reduction of Ni2+ ions, where the particle growth was inhibited by the rigid polymer chain and the formation of smaller particles was favored.

Anatomical consideration of the cardiac plexus to prevent grave bradycardiac arrhythmias associated with lung cancer surgery: a case report.

BACKGROUND: Arrhythmias are known as one of the complications of lung cancer surgery, and most of them are not lethal. Life-threatening arrhythmias have been reported in the literature but in reality very rare. CASE PRESENTATION: A 67-year-old Japanese man with a history of hypertension was diagnosed with squamous cell carcinoma in left lower lobe underwent a left lower lobectomy and bilateral mediastinal lymph node dissection through a median sternotomy. During lymph node dissection along the right vagus nerve, the patient's heart rate and blood pressure dropped suddenly and an electrocardiogram monitor showed ST elevation. These abnormalities returned to normal soon after cardiac massage was performed and a coronary vasodilator was given. A temporary pacing wire was inserted at the end of the surgery. The postoperative course was uneventful and the patient was discharged on postoperative day 11 without a need for permanent pacemaker. CONCLUSIONS: We present a patient who was complicated with lethal arrhythmias during lung cancer surgery for the purpose of elucidating, from anatomical viewpoint, the relationship between arrhythmias and the involvement of cardiac plexus during lymph node dissection. The result showed that arrhythmia was inadvertently elicited by cardiac plexus stimulation during lymph nodes dissection around the vagus nerve. It is important to be familiar not only with the course of phrenic, vagus, and recurrent laryngeal nerve but also the anatomy of cardiac plexus to prevent arrhythmic complications in lung cancer surgery.

Nivolumab-induced myocardial necrosis in a patient with lung cancer: A case report.

A 74-year-old man with lung adenocarcinoma recurrence was admitted to our hospital because of dyspnea 7 days after receiving initial immunotherapy with nivolumab. Electrocardiography revealed ST-segment elevation in V1-6 and echocardiography showed a markedly reduced left ventricular ejection fraction of 9% and akinesis of the anteroseptal wall and apex. He died from acute heart failure 3 days after admission. Microscopically, multiple small foci of myocardial necrosis with few inflammatory cells were scattered in both ventricles. Obstruction of the coronary artery was not identified. We believed that the cause of death was acute heart failure possibly due to nivolumab-induced myocardial necrosis.

Lobe-specific skip nodal metastasis in non-small cell lung cancer patients.

PURPOSE: The purpose of this study is to clarify the lobe-specific nodal metastasis and optimal range of mediastinal nodal dissection in lung cancer patients with skip metastasis. MATERIALS AND METHODS: A total of 136 patients with pN2/3 disease were treated between 1988 and 2002, and these patients were divided into two groups according to whether skip metastasis was identified or not. We drew a comparison of the lobe specificity of mediastinal nodal involvement between skip positive and negative groups. RESULTS: Skip metastasis was identified in 48 (35.3%) of 136 pN2/3 patients. The lymph nodal regions most frequently found (target nodes) were as follows: right upper-#3 and right #4, middle & lower-#3, right #4 and #7, left upper-left #4, #5, and #6, and left lower-#7, #8, and #9. Skip metastasis can be detected at a rate of 82.6% to 91.7% by means of a histological examination of these target nodes. However, the frequency of skip metastasis in other mediastinal nodal regions excluding the target nodes was found to progress to a level of 33.3% to 57.1% insofar as tumor metastasis to these target nodes was identified. CONCLUSIONS: The examination of lobe-specific nodal regions may be helpful for determining patients with skip metastasis. If metastasis is found somewhere in these target nodes, then a systematic nodal dissection may be acceptable for a complete resection even if N1 metastasis is not identified.

Transcatheter aortic valve implantation for patients with lung cancer and aortic valve stenosis.

Many patients who require lung resection have cardiovascular and cerebrovascular comorbidities. It has been recommended that surgical aortic valve replacement (SAVR) should precede lung resection in patients with severe aortic valve stenosis (AS). However, by first undergoing transcatheter aortic valve implantation (TAVI), the patient may undergo lung resection more safely. We present two patients with both severe AS and lung cancer who underwent TAVI and lung resection without any complications.

Quantum Dot Light-Emitting Devices: Beyond Alignment of Energy Levels.

Multinary semiconductor nanoparticles such as CuInS2, AgInS2, and the corresponding alloys with ZnS hold promise for designing future quantum dot light-emitting devices (QLED). The QLED architectures require matching of energy levels between the different electron and hole transport layers. In addition to energy level alignment, conductivity and charge transfer interactions within these layers determine the overall efficiency of QLED. By employing CuInS2-ZnS QDs we succeeded in fabricating red-emitting QLED using two different hole-transporting materials, polyvinylcarbazole and poly(4-butylphenyldiphenylamine). Despite the similarity of the HOMO-LUMO energy levels of these two hole transport materials, the QLED devices exhibit distinctly different voltage dependence. The difference in onset voltage and excited state interactions shows the complexity involved in selecting the hole transport materials for display devices.

Relationship between cortex and pulvinar abnormalities on diffusion-weighted imaging in status epilepticus.

The aim of this study was to analyze the pattern of magnetic resonance diffusion-weighted imaging (DWI) findings in status epilepticus in terms of clinical characteristics. Participants comprised 106 patients with status epilepticus who were admitted to our hospital and underwent DWI. Forty-five patients (42.5 %) showed abnormal findings on DWI and were divided into two groups, comprising 26 patients (24.5 %) with cortex lesions alone and 19 patients (17.9 %) with cortex and pulvinar lesions in the same hemisphere. A long duration of status epilepticus (>120 min) tended to be more prevalent among patients with cortex and pulvinar lesions (57.9 %) than among patients with cortex lesions alone (30.8 %) by univariate and multivariate analyses. Todd's palsy tended to be more frequent in patients with abnormalities on DWI (24/45, 53.3 %) than in patients with normal DWI (21/61, 34.4 %). Six of the 26 patients with cortex lesions alone (23.1 %) had taken anti-epileptic drugs before the attack compared to none of the 19 patients with both cortex and pulvinar lesions. The trend toward a longer duration of status epilepticus in patients with both cortex and pulvinar lesions favors a spreading pattern of seizure discharge from cortex to pulvinar via cortico-pulvinar pathways, and anti-epileptic drugs might, to some extent, prevent spreading of seizure discharge from cortex to pulvinar. In addition, existence of high-intensity areas on DWI at the onset of epilepsy may be a predictive factor for the occurrence of Todd's palsy.

Single-Cell Memory Regulates a Neural Circuit for Sensory Behavior.

Unveiling the molecular and cellular mechanisms underlying memory has been a challenge for the past few decades. Although synaptic plasticity is proven to be essential for memory formation, the significance of "single-cell memory" still remains elusive. Here, we exploited a primary culture system for the analysis of C. elegans neurons and show that a single thermosensory neuron has an ability to form, retain, and reset a temperature memory. Genetic and proteomic analyses found that the expression of the single-cell memory exhibits inter-individual variability, which is controlled by the evolutionarily conserved CaMKI/IV and Raf pathway. The variable responses of a sensory neuron influenced the neural activity of downstream interneurons, suggesting that modulation of the sensory neurons ultimately determines the behavioral output in C. elegans. Our results provide proof of single-cell memory and suggest that the individual differences in neural responses at the single-cell level can confer individuality.

Pulmonary blastoma.

We describe a resected pulmonary blastoma in an 84-year-old male, the oldest of previously reported patients. A chest X-ray showed a 2 cm-sized abnormal shadow in the left lung field. Five months later computed tomography demonstrated a well-demarcated heterogenous mass, measuring 12 cm in diameter, in the left lower lobe of the lung. This mass was diagnosed as a carcinoma using echo-guided percutaneous biopsy. The patient underwent a left lower lobectomy. The resected specimen revealed the tumor to be a pulmonary blastoma arising from lung tissue. Preoperative diagnosis of pulmonary blastoma is extremely difficult because of the histological heterogeneity of tumor. Since it has been noted that pulmonary blastoma rapidly progresses in a short period of time, surgical treatment should be undertaken as quickly as possible when such a tumor is suspected.