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Abstract Introduction Compared to platinum-based therapies, a combination of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) has demonstrated improved outcomes in advanced non-small cell lung cancer (NSCLC), albeit with higher rates of immune-related adverse events (irAEs). This multicenter retrospective study evaluated the efficacy and safety of nivolumab and ipilimumab with or without chemotherapy (NI and NICT) in real-world clinical settings. Methods We enrolled 215 treatment-naïve NSCLC patients who received NI or NICT between December 2020 and May 2023 at 14 institutions in Japan. Severe irAEs (Grade ≥ 3) were assessed using the Common Terminology Criteria for Adverse Events. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan–Meier methods and propensity score matching. Results Of 215 patients, 104 and 111 received NI and NICT, respectively. The median PFS was 5.3 and 5.9 months for NI and NICT, respectively. The median OS was 22.1 and 19.2 months for NI and NICT, respectively. High fever within 3 weeks of treatment initiation and high tumor burden were indicators of severe irAEs. Grade 3 or higher irAEs occurred in 36.5% patients in the NI group and 50.5% patients in the NICT group, with higher treatment-related mortality in the NICT group (5.4% vs. 1.9% in NI). Conclusions NI and NICT showed comparable efficacies in PFS and OS. However, NICT had a higher incidence of severe irAEs and treatment-related mortality. High tumor burden and early high fever were predictors of severe irAEs. Further research is warranted to optimize the efficacy and safety of NICT for NSCLC treatment.

Abstract This retrospective study evaluated the use of laminin γ2 monomer (LG2m) as a predictive biomarker for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection. Serum LG2m levels were measured in two cohorts of patients: cohort 1 comprised 56 patients with chronic liver disease for assessing LG2m stability, whereas cohort 2 included 89 patients with chronic HBV infection who did not have HCC for evaluating the usefulness of LG2m measurement in HCC prediction. LG2m was highly stable in cryopreserved serum, and an increased LG2m level was significantly associated with a higher risk of HCC in chronically HBV-infected patients (P = 0.012). Multivariable Cox regression analysis revealed that high LG2m was an independent significant risk factor for HCC (hazard ratio, 7.16; 95% confidence interval, 1.31–39.2; P = 0.023). These findings suggest that LG2m may serve as a useful biomarker for the prediction of future HCC in patients with chronic HBV infection.

Antigen-specific humoral responses are orchestrated through complex interactions among immune cells in lymphoid tissues, including the collaboration between B cells and T follicular helper (Tfh) cells. Accumulating evidence indicates a crucial role for interleukin-9 (IL-9) in the formation of germinal centers (GCs), enhancing the generation of class-switched high-affinity antibodies. However, the exact function of IL-9 in Tfh cell regulation remains unclear. In this study, we examined the humoral immune responses of CD4Cre/+Il9rafl/fl mice, which lack an IL-9-specific receptor in Tfh cells. Upon intraperitoneal immunization with sheep red blood cells (SRBCs), CD4Cre/+Il9rafl/fl mice displayed diminished levels of SRBC-specific IgG antibodies in their sera, along with reduced levels of GC B cells and plasma cells. Notably, Il9ra-deficient Tfh cells in the spleen exhibited decreased expression of their signature molecules such as B-cell lymphoma 6, C-X-C chemokine receptor 5, IL-4, and IL-21 compared to control mice. In models of allergic asthma induced by house dust mite (HDM) inhalation, CD4Cre/+Il9rafl/fl mice failed to elevate serum levels of HDM-specific IgE and IgG. This was accompanied by reductions in Tfh cells, GC B cells, and plasma cells in mediastinal lymph nodes. Furthermore, group 2 innate lymphoid cells (ILC2s) were identified as producers of IL-9 under immunizing conditions, possibly induced by leukotrienes released by activated IgD+ B cells around the T-B border. These observations may indicate the critical role of IL-9 receptor signaling in the activation of Tfh cells, with ILC2s potentially capable of supplying IL-9 in organized lymphoid tissues.

Abstract Humoral immunity is vital for host protection, yet aberrant antibody responses can trigger harmful inflammation and immune-related disorders. T follicular helper (Tfh) cells, central to humoral immunity, have garnered significant attention for unraveling immune mechanisms. This study shows the role of B-cell Oct-binding protein 1 (Bob1), a transcriptional coactivator, in Tfh cell regulation. Our investigation, utilizing conditional Bob1-deficient mice, suggests that Bob1 plays a critical role in modulating inducible T-cell costimulator expression and cellular respiration in Tfh cells. This regulation maintains the long-term functionality of Tfh cells, enabling their reactivation from central memory T cells to produce antibodies during recall responses. In a bronchial asthma model induced by house dust mite (HDM) inhalation, Bob1 is observed to enhance HDM-specific antibodies, including IgE, highlighting its pivotal function in Tfh cell regulation. Further exploration of Bob1-dependent mechanisms in Tfh cells holds promise for governing protective immunity and addressing immune-related disorders.

The relationships between T follicular helper (Tfh) cells and antigen-specific immunoglobulins (sIgs) in patients with allergic respiratory diseases who are receiving antigen immunotherapy (AIT) have not been fully clarified. Therefore, we started to perform house dust mite sublingual immunotherapy (HDM-SLIT) for 20 patients with atopic asthma comorbid with allergic rhinitis (AA+AR) who were already receiving ordinary treatments including inhaled corticosteroid (ICS). We examined percentages of circulating T follicular helper (cTfh) and regulatory (cTfr) cells and percentages of circulating regulatory T (cTreg) and B (cBreg) cells by FACS and we examined levels of Der-p/f sIgs by ELISA. Based on the symptom score (asthma control questionnaire: ACQ) and medication score ((global initiative for asthma: GINA) treatment step score) in patients with AA, the patients were divided into responders and non-responders. The percentage of cTfh2 cells significantly decreased and the percentage of cTfh1 cells significantly increased within the first year. Der-p/f sIgEs decreased after a transient elevation at 3 months in both groups. Notably, the percentage of cTfh2 cells and the ratio of cTfh2/cBreg cells and Der-p/f sIgEs greatly decreased in responders from 6 months to 12 months. The percentages of cTfr and cTreg cells showed significant negative correlations with the percentage of cTfh2 cells. The percentage of IL-4+ cTfh cells were significantly decreased and the percentage of IFN-γ+ cTfh cells were increased before treatment to 24 months in 6 patients examined (4 responders and 2 non-responders). We performed multi plelogistic regression analysis based on these results, the ratios of cTfh2/cTfr cells and cTfh2/cBreg cells at the start of therapy were statistically effective biomarkers for predicting the response to HDM-SLIT in patients with AA+AR.

Abstract Monomorphic epitheliotropic intestinal T‐cell lymphoma (MEITL) is a very rare intestinal T‐cell lymphoma which is observed most frequently in the jejunum. MEITL is prone to cause intestinal perforation and the prognosis is very poor when it occurs. Here we report a fatal case of MEITL causing jejunal perforation at the time of diagnosis in a 79‐year‐old man. The patient underwent emergency surgery for jejunal perforation caused by MEITL but died 3 months after the initial visit due to prolonged peritonitis. It is desirable to establish a method to predict cases with intestinal perforation, and systematize the treatment strategies to avoid perforation.

Alzheimer’s disease, type 2 diabetes, and non-alcoholic steatohepatitis (NASH) constitute increasingly prevalent disorders. Individuals with type 2 diabetes are well-known to be susceptible to Alzheimer’s disease. Although the pathogenesis of each disorder is multifactorial and the causal relation remains poorly understood, reactive oxygen species (ROS)-induced lipid and protein oxidation conceivably plays a common role. Lipid peroxidation product was recently reported to be a key factor also for non-alcoholic steatohepatitis, because of inducing hepatocyte degeneration/death. Here, we focus on implication of the representative lipid-peroxidation product ‘hydroxynonenal’ for the cell degeneration/death of brain, pancreas, and liver. Since Hsp70.1 has dual roles as a chaperone and lysosomal membrane stabilizer, hydroxynonenal-mediated oxidative injury (carbonylation) of Hsp70.1 was highlighted. After intake of high-fat diets, oxidation of free fatty acids in mitochondria generates ROS which enhance oxidation of ω-6 polyunsaturated fatty acids (PUFA) involved within biomembranes and generate hydroxynonenal. In addition, hydroxynonenal is generated during cooking deep-fried foods with vegetable oils especially containing linoleic acids. These intrinsic and exogenous hydroxynonenal synergically causes an increase in its serum and organ levels to induce Hsp70.1 oxidation. As it is amphiphilic; being water-soluble but displays strong lipophilic characteristics, hydroxynonenal can diffuse within the cells and react with targets like senile and/or atheromatous plaques outside the cells. Hydroxynonenal can deepen and expand lysosomal injuries by facilitating ‘calpain-mediated cleavage of the carbonylated Hsp70.1’. Despite the unique anatomical, physiological, and biochemical characteristics of each organ for its specific disease, there should be a common cascade of the cell degeneration/death which is caused by hydroxynonenal. This review aims to implicate hydroxynonenal-mediated Hsp70.1 carbonylation for lysosomal membrane permeabilization/rupture and the resultant cathepsin leakage for inducing cell degeneration/death. Given the tremendous number of worldwide people suffering various lifestyle-related diseases, it is valuable to consider how ω-6 PUFA-rich vegetable oils is implicated for the organ disorder.

T follicular helper (Tfh) cells drive humoral immunity by facilitating B cell responses at the initial and recall phases. Recent studies have indicated the possible involvement of Tfh cells in the process of chronic inflammation. However, the functional role of Tfh cells in persistent immune settings remains unclear. Here, we report that CD4+CD8+ (double-positive, DP; CD3+CD4+CD8+CXCR5hiPD-1hi) Tfh cells, a subset of germinal-center-type Tfh cells, were abundantly present in the fibroinflammatory lesions of patients with immunoglobulin G4-related disease (IgG4-RD). Transcriptome analyses showed that these DP-Tfh cells in the lesions of IgG4-RD preferentially expressed signature genes characteristic of cytotoxic CD8+ T cells, such as Eomes, CRTAM, GPR56, and granzymes, in addition to CD70. Scatter diagram analyses to examine the relationships between tissue-resident lymphocytes and various clinical parameters revealed that the levels of DP-Tfh cells were inversely correlated to the levels of serum IgG4 and local IgG4-expressing (IgG4+) memory B cells (CD19+CD27+IgD-) in patients with IgG4-RD. Cell culture experiments using autologous tonsillar lymphocytes further suggested that DP-Tfh cells possess a poor B-cell helper function and instead regulate memory B cells. Since CD4+ (single positive, SP; CD3+CD4+CD8-CXCR5hiPD-1hi) Tfh cells differentiated into DP-Tfh cells under stimulation with IL-2 and IL-7 as assessed by in vitro experiments, these data imply that SP-Tfh cells are a possible origin of DP-Tfh cells under persistent inflammation. These findings highlight the potential feedback loop mechanism of Tfh cells in immune tolerance under chronic inflammatory conditions. Further studies on DP-Tfh cells may facilitate control of unresolved humoral responses in IgG4-RD pathological inflammation.

Aim. Cytomegalovirus (CMV) can cause hepatitis, encephalomyelitis, and pneumonitis in immunocompromised patients. In contrast, CMV infection of immunocompetent patients can lead to the development of infectious mononucleosis and is typically self-limiting; severe complications are rare. We evaluated the pathophysiology and immunological aspects of CMV hepatitis in recently immunocompetent adult patients. Methods. We examined the clinical features and outcomes of 47 adult immunocompetent patients with CMV hepatitis (29 men, 18 women; mean age, 34 ± 11 years) from January 2005 to August 2019 treated in our hospital. We also assayed T-cell activation to evaluate the immune responses in these patients. Results. Fever (74.5%), hepatosplenomegaly (74.5%), sore throat (36.2%), headache (31.9%), abdominal pain (27.7%), lymphadenopathy (23.4%), and skin rash (6.4%) were present at admission. Complications included gastrointestinal injury (25.5%), neuropathy (4.3%), thrombocytopenia (2.1%), and splenic infarction (2.1%). All patients had a good clinical course without liver failure or transition to chronic liver injury. The time to recover from liver injury ranged from 12 to 142 days (mean, 43.4 ± 28.7 days). The serum sIL-2R level, which reflects T-cell activation, was transiently elevated and correlated with the extent of hepatic inflammation. Conclusions. CMV hepatitis in immunocompetent individuals has a satisfactory outcome, but occasionally results in complications in other organs. The sIL-2R level has potential as a surrogate marker of hepatic inflammation in immunocompetent patients with CMV hepatitis.

T follicular helper (Tfh) cells drive humoral immunity by facilitating B cell responses at the initial and recall phases. Recent studies have indicated the possible involvement of Tfh cells in the process of chronic inflammation. However, the functional role of Tfh cells in persistent immune settings remains unclear. Here, we report that CD4+CD8+ (double-positive, DP; CD3+CD4+CD8+CXCR5hiPD-1hi) Tfh cells, a subset of germinal-center-type Tfh cells, were abundantly present in the fibroinflammatory lesions of patients with immunoglobulin G4-related disease (IgG4-RD). Transcriptome analyses showed that these DP-Tfh cells in the lesions of IgG4-RD preferentially expressed signature genes characteristic of cytotoxic CD8+ T cells, such as Eomes, CRTAM, GPR56, and granzymes, in addition to CD70. Scatter diagram analyses to examine the relationships between tissue-resident lymphocytes and various clinical parameters revealed that the levels of DP-Tfh cells were inversely correlated to the levels of serum IgG4 and local IgG4- expressing (IgG4+) memory B cells (CD19+CD27+IgD-) in patients with IgG4-RD. Cell culture experiments using autologous tonsillar lymphocytes further suggested that DP-Tfh cells possess a poor B-cell helper function and instead regulate memory B cells. Since CD4+ (single positive, SP; CD3+CD4+CD8-CXCR5hiPD-1hi) Tfh cells differentiated into DP-Tfh cells under stimulation with IL-2 and IL-7 as assessed by in vitro experiments, these data imply that SP-Tfh cells are a possible origin of DP-Tfh cells under persistent inflammation. These findings highlight the potential feedback loop mechanism of Tfh cells in immune tolerance under chronic inflammatory conditions. Further studies on DP-Tfh cells may facilitate control of unresolved humoral responses in IgG4-RD pathological inflammation. [ABSTRACT FROM AUTHOR]

Abstract Background Pulmonary extended segmentectomy is an optional surgical treatment for early-stage non-small cell lung cancer that helps to achieve optimal surgical margins. Here, we describe a challenging instance of extended segmentectomy via uniportal video-assisted thoracic surgery with virtual-assisted lung mapping, a preoperative bronchoscopic dye marking procedure. Case presentation A 72-year-old woman presented with two tumors that were clinically diagnosed as early-stage lung cancer; extended right apical segmentectomy was indicated. Because the tumors had appeared unidentifiable intraoperatively, we performed virtual-assisted lung mapping for tumor localization and delineation of the optimal resection area. Surgery was conducted through a single port. All virtual-assisted lung mapping markings were visible. After dissection of the apical vessels and bronchi, a putative intersegmental line was determined using collateral ventilation. Based on the putative intersegmental plane identified by collateral ventilation and the virtual-assisted lung mapping markings, the resection line was delineated. Extended apical segmentectomy along the resection line was successfully performed via uniportal video-assisted thoracic surgery. The postoperative course was uneventful. The pathological diagnosis was minimally invasive adenocarcinoma and adenocarcinoma in situ. Conclusions Virtual-assisted lung mapping can help to achieve optimal extended segmentectomy via uniportal video-assisted thoracic surgery.

Abstract Background Pulmonary segmentectomy for a lung with an incomplete interlobar fissure may complicate persistent air leakage. The fissureless technique is often used in lobectomy to prevent persistent air leakage. We herein describe successful use of the fissureless technique for segmentectomy with the aid of a robotic surgical system. Case presentation A 63-year-old man was clinically diagnosed with early-stage lung cancer for which lingular segmentectomy was indicated. A preoperative image revealed a lung with an incomplete fissure. Based on three-dimensional reconstruction imaging, we planned to divide the hilum structures in the order of the pulmonary vein, bronchus, and pulmonary artery and finally resect the lung parenchyma by dividing the intersegmental plane and interlobar fissure. This fissureless technique was successfully conducted using a robotic surgical system. The patient did not develop persistent air leakage and was alive without recurrence 1 year after segmentectomy. Conclusions The fissureless technique may be a useful option in segmentectomy for a lung with an incomplete interlobar fissure.

Surface-enhanced Raman spectroscopy (SERS) provides insights into electrode reaction processes due to its high selectivity towards the interface. It is necessary to ensure a stable and inexpensive supply of sensors to make this method more widely applicable. Techniques based on electrochemistry are efficient and suitable for mass manufacturing. In this research, two electroless processes for depositing Ag nanoparticles (NPs) on a glass substrate for sensor fabrication are discussed: one using ascorbic acid, the other hypophosphite. Specifically, the process using hypophosphite was achieved by forming Pd nuclei in the activating process. It turned out that when the ascorbic acid sensor is applied, undesired SERS signals originating from the reductant appear. By contrast, the hypophosphite sensor greatly reduces the unwanted signals. The optimized plasmonic sensor can achieve in situ SERS observation of electrochemical reactions without being restricted by electrode material and morphology.

Pulmonary artery aneurysms (PAAs) occurring in the distal branch of the pulmonary artery are rare, and there are only a few reports of transcatheter embolization of unruptured idiopathic peripheral PAAs. We report a case of a 66-year-old woman with a history of surgery for pulmonary arteriovenous malformations who presented with an idiopathic peripheral PAA of A10 confirmed by contrast-enhanced computed tomography and pulmonary artery angiography. Transcatheter embolization was performed to prevent rupture, and the aneurysm was successfully embolized. Although there is no consensus on the indications and treatment for unruptured idiopathic peripheral PAAs, transcatheter embolization may be a favorable treatment option.

Abstract Rapid identification of lung-cancer micro-lesions is becoming increasingly important to improve the outcome of surgery by accurately defining the tumor/normal tissue margins and detecting tiny tumors, especially for patients with low lung function and early-stage cancer. The purpose of this study is to select and validate the best red fluorescent probe for rapid diagnosis of lung cancer by screening a library of 400 red fluorescent probes based on 2-methyl silicon rhodamine (2MeSiR) as the fluorescent scaffold, as well as to identify the target enzymes that activate the selected probe, and to confirm their expression in cancer cells. The selected probe, glutamine-alanine-2-methyl silicon rhodamine (QA-2MeSiR), showed 96.3% sensitivity and 85.2% specificity for visualization of lung cancer in surgically resected specimens within 10 min. In order to further reduce the background fluorescence while retaining the same side-chain structure, we modified QA-2MeSiR to obtain glutamine-alanine-2-methoxy silicon rhodamine (QA-2OMeSiR). This probe rapidly visualized even borderline lesions. Dipeptidyl peptidase 4 and puromycin-sensitive aminopeptidase were identified as enzymes mediating the cleavage and consequent fluorescence activation of QA-2OMeSiR, and it was confirmed that both enzymes are expressed in lung cancer. QA-2OMeSiR is a promising candidate for clinical application.

Introduction: Lung cancer presenting as ground-glass nodules (GGNs) with little consolidation is often diagnosed as noninvasive carcinoma. Increasing evidence suggests that sublobar lung resection, such as wedge resection, provides satisfactory long-term outcomes equivalent to those of lobectomy. Spread through alveolar spaces (STAS) is a reported risk factor for recurrence, especially when sublobar lung resection is applied. We herein report a rare case of a pure GGN that was histologically confirmed to be adenocarcinoma in situ (AIS) and associated STAS after limited resection. Case presentation: A 67-year-old woman presented with an 8-mm pure GGN in S2 of the right upper lobe and a part-solid GGN in S8 of the right lower lobe. The clinical stages of these GGNs were TisN0M0 stage 0 and T1aN0M0 stage IA1, respectively. The patient underwent video-assisted thoracoscopic segmentectomies of S2 and S8. Histopathological examination of the resected specimens revealed minimally invasive adenocarcinoma in S8 and AIS in S2. Stromal invasion was not observed in the tumor located in S2, but a tumor cell cluster was found in the air space located away from the AIS lesion. Thus, the lesion was positive for STAS. Conclusion: We have reported a rare case of a pure GGN that was histologically STAS-positive, otherwise diagnosed as AIS after limited resection.

Abstract Background Various approaches have been used to assist and facilitate segmentectomy with favorable oncological outcomes. We describe a hybrid approach comprising virtual-assisted lung mapping (VAL-MAP), which is a preoperative bronchoscopic dye-marking technique, combined with systemic indocyanine green (ICG) injection. Clinical presentation An asymptomatic 64-year-old man was referred to our department because of a lung nodule detected during his annual medical checkup. The chest computed-tomography image revealed a 16-mm, partly solid, ground-glass nodule in the left segment 4. Because the nodule was hardly palpable and deeply located between the left upper division segment and the left lingular segment, we performed VAL-MAP to facilitate extended left lingulectomy. Five dye markings were undertaken preoperatively. Surgery to remove the nodule was then conducted via complete three-port video-assisted thoracic surgery. The VAL-MAP markings were easily identified intraoperatively and helped locate the nodule. The intersegmental plane was identified by the ICG injection. The resection line was determined based on the intersegmental plane identified by the ICG injection and the site of the nodule suggested by the VAL-MAP markings. Following the resection line, we thoracoscopically achieved extended lingulectomy with sufficient surgical margins. The patient was discharged with no complications. The pathological diagnosis was adenocarcinoma in situ. Conclusion The hybrid technique of VAL-MAP and systemic ICG injection can be useful for accomplishing successful extended segmentectomy.

Abstract Background Pulmonary segmentectomy can be challenging when thoracic surgeons encounter anatomical anomalies. A displaced left apicoposterior bronchus is a rare bronchial anomaly that makes lung anatomical resection challenging. We herein present a case of successful left apicoposterior segmentectomy for lung cancer in a patient with an anomalous segmental bronchus. Case presentation A 70-year-old man was clinically diagnosed with early-stage lung cancer for which segmentectomy was indicated. A preoperative image revealed a displaced left apicoposterior bronchus that branched behind the left main pulmonary artery. With the aid of three-dimensional reconstruction imaging and systemic indocyanine green injection, we successfully performed left apicoposterior segmentectomy under complete video-assisted thoracic surgery. The pathological diagnosis was adenocarcinoma. The patient was alive without recurrence 8 months after segmentectomy. Conclusion Preoperative three-dimensional imaging and systemic indocyanine green injection enabled us to successfully conduct challenging segmentectomy in a patient with an anomalous bronchus.

A much higher cell voltage of ca. 2.5 V than that of the typical Li-S battery was successfully achieved by combining the 5 V-class, spinel-type LiNi0.5Mn1.5O4 (LNMO) as a cathode and the rubber-derived sulfur composite as an anode. The cycling performance of the cell was improved by the PVDF coating only the cathode and coating both the cathode and anode, in which the discharge capacity retention increased from ca. 45 % to ca. 60 %. On the other hand, there was no difference in the cycling performance between the cell with the PVDF coating only the anode and the cell without the PVDF coating both the cathode and anode. There was no difference between the cycling performance of the half-cell of the LNMO cathode with the PVDF coating and without the PVDF coating, indicating that the PVDF coating on the cathode side does not prevent degradation of the electrolyte solution on the cathode surface. These results suggest that the PVDF coatings of the cathode surface play an important role as a protective layer in preventing the direct contact and side reaction between the polysulfides and cathode surface, thus leading to improvement of the cycling performance.

A rubber-derived sulfur composite cathode material for the Li-S battery/Li-ion battery was synthesized by the vulcanization process of butadiene rubber as a polymer source and a large amount of sulfur. In this study, the higher vulcanization temperature of 450 °C and a larger amount of sulfur (rubber : sulfur = 1 : 10, mass/mass) than the mass production process of the rubber were applied. The rubber-derived sulfur composite has a large amount of sulfur, ca. 58 wt% and a stable cycling ability with a capacity of 400 mAh g−1 at 30 °C. The cells consisting of the rubber-derived sulfur composite as the cathode and SiO as the anode displayed a great potential as for the next-generation LIBs because of its both electrodes containing no transition metals, outstanding electrochemical properties and safety performance. The cell showed a superior high and low temperature performance from −20–80 °C for over 100 cycles and a good rate performance in which the capacity of ca. 600 mAh g−1 was obtained at the 5 C-rate at 60 °C. In addition, there were no thermal runaway and no evolution of hydrogen sulfide in the nail penetration test.

Abstract A bronchosubcutaneous fistula (BF) is an abnormal communication between the bronchus, pleural cavity, and subcutaneous tissue. Treatment of BF has been documented rarely. We describe a successful endoscopic bronchial occlusion using endobronchial Watanabe spigots (EWSs) for BF manifesting as massive subcutaneous emphysema (SE). A 78‐year‐old woman developed delayed localized SE following a surgical pleural biopsy for the diagnosis of primary lung cancer. Computed tomography (CT) of the chest revealed BFs resulting from pleural biopsy. The affected bronchi were identified using chest CT. We inserted EWSs into the affected bronchi with the aid of virtual bronchoscopic navigation. This bronchoscopic procedure achieved complete resolution of the SE by sealing the BFs without the need for surgical interventions.

Abstract Background Virtual-assisted lung mapping is a novel bronchoscopic lung marking technique that uses virtual images to perform multiple concurrent dye marking of barely palpable pulmonary tumors. Subsequent chest computed tomography is required to confirm the locations marked. We here report a patient in whom computed tomography after virtual-assisted lung mapping unexpectedly revealed additional tiny pulmonary nodules. Case presentation A 64-year-old woman with a history of renal cell carcinoma presented with two pulmonary nodules suspicious of metastases from renal cell carcinoma. Because we anticipated that the nodules would be difficult to palpate intraoperatively, we performed virtual-assisted lung mapping prior to attempting to resect them. Computed tomography after mapping unexpectedly detected two additional nodules. Although the existing markings did not relate to the newly found nodules, we used imaginary auxiliary lines and anatomical landmarks to extend the lung map to incorporate the unexpected nodules. The additional nodules were successfully resected by thoracoscopic wedge resection. Pathologic examination identified all nodules as metastases from renal cell carcinoma, and the surgical margins were negative. Conclusions Imaginary auxiliary lines and anatomical landmarks extended the existing lung map of virtual-assisted lung mapping, enabling resection of unexpected pulmonary nodules found in post-mapping computed tomography images.

Good's syndrome is a rare condition of immunodeficiency that is characterized by thymoma and hypogammaglobulinemia. A 74-year-old Japanese woman underwent total thymothymectomy for type AB thymoma (2015 WHO classification). She developed recurrent infectious diseases caused by Escherichia coli (bacteremia), Streptococcus pneumoniae (pneumonia and bacteremia) and Pseudomonas aeruginosa (bacteremia) in the year after thymectomy. The serum levels of immunoglobulin were significantly low (IgG 157mg/dL), which suggested that her infectious diseases were associated with Good's syndrome. Although she began receiving intravenous immunoglobulin every four weeks, she died of pneumonia a week after the second administration of immunoglobulin. When physicians encounter patients with recurrent infection who have a medical history of thymoma, the detection of hypogammaglubulinemia can be a key clue to the diagnosis of Good's syndrome. Keywords: Good's syndrome, Thymoma, Immunodeficiency, Hypogammaglobulinemia

We fabricated nanosized KMgF3 single crystals via a dry pulsed laser ablation process using femtosecond laser pulses. The sizes, shapes, and crystallographic properties of the crystals were evaluated by transmission electron microscopy (TEM). Almost all of the particles were spherical with diameters of less than 100 nm, and they were not highly agglomerated. Selected-area electron diffraction and high-resolution TEM analyses showed that the particles were single crystals. Particle diameter was controlled within a wide range by adjusting the Ar ambient gas pressure. Under low gas pressures (1 and 10 Pa), relatively small particles (primarily 10 nm or less) were observed with a high number density. With increasing pressure, the mean diameter increased and the number density drastically decreased. Vacuum-ultraviolet cathodoluminescence was observed at 140–230 nm with blue shift and broadening of spectrum.

Altered protein expression and phosphorylation are common events during malignant transformation. These perturbations have been widely explored in the context of E-cadherin cell-cell adhesion complexes, which are central in the maintenance of the normal epithelial phenotype. A major component of these complexes is p120 catenin (p120), which binds and stabilizes E-cadherin to promote its adhesive and tumor suppressing function. However, p120 is also an essential mediator of pro-tumorigenic signals driven by oncogenes, such as Src, and can be phosphorylated at multiple sites. Although alterations in p120 expression have been extensively studied by immunohistochemistry (IHC) in the context of tumor progression, little is known about the status and role of p120 phosphorylation in cancer. Here we show that tyrosine and threonine phosphorylation of p120 in two sites, Y228 and T916, is elevated in renal and breast tumor tissue samples. We also show that tyrosine phosphorylation of p120 at its N-terminus, including at the Y228 site is required for its pro-tumorigenic potential. In contrast, phosphorylation of p120 at T916 does not affect this p120 function. However, phosphorylation of p120 at T916 interferes with epitope recognition of the most commonly used p120 antibody, namely pp120. As a result, this antibody selectively underrepresents p120 levels in tumor tissues, where p120 is phosphorylated. Overall, our data support a role of p120 phosphorylation as a marker and mediator of tumor transformation. Importantly, they also argue that the level and localization of p120 in human cancer tissues immunostained with pp120 needs to be re-evaluated.

We demonstrated a field emission lamp by employing a KMgF3 thin film as a solid-state vacuum ultraviolet phosphor. The output power of the lamp was 2 μW at an extraction voltage of 800 V and acceleration voltage of 1800 V, and it operated at wavelengths 140–220 nm, which is the shortest wavelength reported for solid-state phosphor lamps. The thin film was grown on MgF2 substrate by pulsed laser deposition. Its conversion efficiency was almost equivalent to a single KMgF3 crystal, and it had emission peaks of 155 and 180 nm in wavelength. These peaks are attributed to transitions from the valence anion band to the outermost core cation band and correspond well with emission peaks previously reported from the crystal. Additionally, we obtained a thermal-free and low-power consumption lamp by employing carbon nanofibres (CNFs) as a field emitter. A CNF emitter was easily grown at room temperature and can be grown on flexible materials.

A vacuum ultraviolet (VUV) field emission lamp was developed by using a neodymium ion doped lutetium fluoride (Nd3+ : LuF3) thin film as solid-state phosphor and carbon nanofiber field electron emitters. The thin film was synthesized by pulsed laser deposition and incorporated into the lamp. The cathodoluminescence spectra of the lamp showed multiple emission peaks at 180, 225, and 255 nm. These emission spectra were in good agreement with the spectra reported for the Nd3+ : LuF3 crystal. Moreover, application of an acceleration voltage effectively increased the emission intensity. These results contribute to the performance enhancement of the lamp operating in the VUV region.

The juxtaglomerular cell tumor (JGCT) is a rare renal tumor characterized by excessive renin secretion causing intractable hypertension and hypokalemia. However, asymptomatic nonfunctioning JGCT is extremely rare. Here, we report a case of nonfunctioning JGCT in a 31-year-old woman. The patient presented with a left renal tumor without hypertension or hypokalemia. Under a clinical diagnosis of renal cell carcinoma, radical nephrectomy was performed. The tumor was located in the middle portion adjacent to the renal pelvis, measuring 2 cm in size. Pathologically, the tumor was composed of cuboidal cells forming a solid arrangement, immunohistochemically positive for renin. Based on these findings, the tumor was diagnosed as JGCT. In cases with hyperreninism, preoperative diagnosis of JGCT is straightforward but difficult in nonfunctioning case. Generally, JGCT presents a benign biological behavior. Therefore, we should take nonfunctioning JGCT into the differential diagnoses for renal tumors, especially in younger patients to avoid excessive surgery.