One-Month Dual Antiplatelet Therapy Followed by P2Y12 Inhibitor Monotherapy After Biodegradable Polymer Drug-Eluting Stent Implantation　- The REIWA Region-Wide Registry.

BACKGROUND: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain.Methods and Results: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. CONCLUSIONS: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.

Tracheomediastinal fistula induced by concurrent chemoradiotherapy in small cell lung cancer: A case report and literature review.

Tracheomediastinal fistula is a rare but life-threatening complication of cancer. We report a case of tracheomediastinal fistula induced by concurrent chemoradiotherapy in limited stage small cell lung cancer. Despite the treatment response, the metastatic paratracheal lymph node increased gradually during concurrent chemoradiotherapy, resulting in the occurrence of tracheomediastinal fistula and mediastinitis. Without any surgical intervention, the patient achieved successful recovery from mediastinitis through antibiotic treatment, although the tracheomediastinal fistula remained open. In this report, we also review previous studies of tracheomediastinal and bronchomediastinal fistulas and summarize the clinical features.

TP53 gain-of-function mutations promote osimertinib resistance via TNF-α-NF-κB signaling in EGFR-mutated lung cancer.

EGFR tyrosine kinase inhibitors (TKIs) are effective against EGFR-mutated lung cancer, but tumors eventually develop resistance to these drugs. Although TP53 gain-of-function (GOF) mutations promote carcinogenesis, their effect on EGFR-TKI efficacy has remained unclear. We here established EGFR-mutated lung cancer cell lines that express wild-type (WT) or various mutant p53 proteins with CRISPR-Cas9 technology and found that TP53-GOF mutations promote early development of resistance to the EGFR-TKI osimertinib associated with sustained activation of ERK and expression of c-Myc. Gene expression analysis revealed that osimertinib activates TNF-α-NF-κB signaling specifically in TP53-GOF mutant cells. In such cells, osimertinib promoted interaction of p53 with the NF-κB subunit p65, translocation of the resulting complex to the nucleus and its binding to the TNF promoter, and TNF-α production. Concurrent treatment of TP53-GOF mutant cells with the TNF-α inhibitor infliximab suppressed acquisition of osimertinib resistance as well as restored osimertinib sensitivity in resistant cells in association with attenuation of ERK activation and c-Myc expression. Our findings indicate that induction of TNF-α expression by osimertinib in TP53-GOF mutant cells contributes to the early development of osimertinib resistance, and that TNF-α inhibition may therefore be an effective strategy to overcome such resistance in EGFR-mutant lung cancer with TP53-GOF mutations.

Effect of porphyrin ligands on the catalytic CH4 oxidation activity of monocationic µ-nitrido-bridged iron porphyrinoid dimers by using H2O2 as an oxidant.

The µ-nitrido-bridged iron phthalocyanine homodimer is a potent molecule-based CH4 oxidation catalyst that can effectively oxidize chemically stable CH4 under mild reaction conditions in an acidic aqueous solution including an oxidant such as H2O2. The reactive intermediate is a high-valent iron-oxo species generated upon reaction with H2O2. However, a detailed comparison of the CH4 oxidation activity of the µ-nitrido-bridged iron phthalocyanine dimer with those of µ-nitrido-bridged iron porphyrinoid dimers containing one or two porphyrin ring(s) has not been yet reported, although porphyrins are the most important class of porphyrinoids. Herein, we compare the catalytic CH4 and CH3CH3 oxidation activities of a monocationic µ-nitrido-bridged iron porphyrin homodimer and a monocationic µ-nitrido-bridged heterodimer of an iron porphyrin and an iron phthalocyanine with those of a monocationic µ-nitrido-bridged iron phthalocyanine homodimer in an acidic aqueous solution containing H2O2 as an oxidant. It was demonstrated that the CH4 oxidation activities of monocationic µ-nitrido-bridged iron porphyrinoid dimers containing porphyrin ring(s) were much lower than that of a monocationic µ-nitrido-bridged iron phthalocyanine homodimer. These findings suggested that the difference in the electronic structure of the porphyrinoid rings of monocationic µ-nitrido-bridged iron porphyrinoid dimers strongly affected their catalytic light alkane oxidation activities.

Osimertinib readministration for central nervous system metastases in non-small cell lung cancer positive for EGFR activating mutations.

BACKGROUND: Osimertinib shows pronounced efficacy for EGFR mutation-positive non-small cell lung cancer (NSCLC) including associated central nervous system (CNS) metastases. Tumors inevitably develop resistance to the drug, however. Osimertinib is sometimes readministered after completion of standard chemotherapy. To clarify which patients might receive benefit from osimertinib readministration, we have retrospectively assessed its efficacy with a focus on CNS metastases. METHODS: A retrospective analysis of medical records was performed for 21 patients who underwent osimertinib readministration at Kyushu University Hospital between March 2016 and April 2023. CNS metastases were evaluated according to modified Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Among the 21 enrolled patients, 16 individuals had target lesions on the basis of RECIST. One (6.3%) of these 16 patients achieved a partial response to osimertinib readministration, with the remaining 15 patients showing stable or progressive disease. The median overall progression-free survival (PFS) and median overall survival for all 21 patients were 3.8 and 13.9 months, respectively. The efficacy of osimertinib readministration for CNS metastases was evaluable in eight patients including five individuals with leptomeningeal metastases. The objective response rate for CNS metastases and the improvement rate for leptomeningeal metastases were both 100%. The median PFS with regard to CNS or non-CNS lesions for these eight patients was 24.7 and 10.5 months, respectively. CONCLUSIONS: Osimertinib readministration showed limited efficacy for non-CNS lesions but excellent efficacy for CNS metastases, suggesting that such treatment is an option for EGFR-mutated NSCLC patients with CNS metastases.

Anatomical features of a crossing vein connecting left and right internal mammary veins: A preliminary study with computerized tomography or magnetic resonance imaging.

BACKGROUND: In breast reconstruction with free flaps, retrograde venous anastomosis into the internal mammary vein (IMV) is often unavoidable. Utility of a crossing vein between the right and left IMV, one of the anatomical foundations which make retrograde flow possible, has been reported but only with a few detailed features. This study evaluated the presence, actual location, and diameter of the crossing veins using preoperative imaging such as contrast-enhanced computed tomography (CECT), or contrast-enhanced magnetic resonance imaging (CEMRI). Moreover, this is a preliminary non-invasive study to clarify these processes on a larger scale. METHODS: We included 29 cases of unilateral breast reconstruction performed between July 2018 and September 2023 at our institution using unipedicled or bipedicled free deep inferior epigastric artery perforator (DIEP) flaps with retrograde venous anastomosis to only one IMV at the level of anastomosis. No congestion or necrosis was observed. In the final 24 cases with sufficient imaging coverage of preoperative contrast-enhanced images (15 CECT and 9 CEMRI), the crossing veins of IMVs were detected and the number, localization, and diameter were measured. RESULTS: In 20 cases of 24 images, the crossing veins between IMVs were completely identified (83%). In 18 of the cases, only one crossing vein was established immediately ventral to the xiphoid process, averaging 19.3 ± 7.18 mm caudal to the fibrous junction between the sternal body and xiphoid process. The average diameter of the veins was 1.57 ± 0.42 mm. In two other cases, the second crossing vein originated on the dorsal surface of the sternum, but it was a very thin vein of about 0.4 mm. Three images indicated incomplete identification of the crossing vein at the xiphoid process, and in one case, no crossing vein was observed between bilateral IMVs. CONCLUSION: The contrast-enhanced imaging study revealed an anatomic feature that the crossing veins (about 1.5 mm in diameter) connecting the right and left IMVs are located just ventral to the xiphoid process. Furthermore, the crossing veins can be identified on contrast-enhanced images, and refinement of this method is expected to lead to future non-invasive anatomical investigations in an even larger number of cases.

A case of inflammatory myofibroblastic tumor harboring EML4-ALK fusion with a brain metastasis responding to alectinib.

Metastatic inflammatory myofibroblastic tumor (IMT) is very rare and detailed reports on diagnosis and treatment are limited. Here, we report a case of metastatic IMT with ALK rearrangement. A 73-year-old woman was diagnosed with IMT involving a brain metastasis. Next generation sequencing (NGS) panel testing with Oncomine dx target test revealed that her tumor was positive for EML4-ALK. Treatment with alectinib was initiated, resulting in remarkable shrinkage of both the primary tumor and the brain metastasis. This report is the first to identify ALK rearrangement in IMT using a commercially available NGS panel testing, followed by treatment with alectinib. This case suggests that NGS panel testing may be useful in the diagnosis and treatment of patients with metastatic IMT.

Measurement of Bisphenol A Diglycidyl Ether (BADGE), BADGE derivatives, and Bisphenol F Diglycidyl Ether (BFDGE) in Japanese infants with NICU hospitalization history.

BACKGROUND: Bisphenol A diglycidyl ether (BADGE) and Bisphenol F diglycidyl ether (BFDGE) are used in medical devices, such as intravenous sets, syringes, and catheters. Several studies have reported that these compounds are endocrine disruptors, cytotoxic, and genotoxic, raising concerns about their adverse effects on infants, in a stage of remarkable growth and development. The present study aimed to measure the serum concentrations of BADGE, derivatives of BADGE, and BFDGE in infants and examine the factors that influence them. METHODS: Ten infants admitted to the neonatal intensive care unit (NICU) were enrolled in the present study. Blood samples from each infant and questionnaires from their mothers were collected twice, at 1-2 months and 7 months of age. BADGE, BADGE·H2O, BADGE·2H2O, and BFDGE were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Serum BADGE·2H2O was identified in all infants, at both 1-2 months (2.30-157.58 ng/ml) and 7 months of age (0.86-122.85 ng/ml). One of the two infants who received invasive ventilation showed a substantially increased BADGE·2H2O concentration. There was no significant difference in BADGE·2H2O concentrations at 7 months of age between the group that ate commercial baby food at least ≥ 1 time per week and the group that did not. CONCLUSIONS: BADGE·2H2O was detected in the serum of all infants with a history of NICU hospitalization. Future studies are needed to determine the source of BADGE exposure and investigate its effects on infant development.

Objective Assessment of the Repeated Botox Treatment to the Synkinesis of Facial Paralysis by the Integrated Electromyography.

BACKGROUND: The widely used botox type A (BTX-A) is effective against synkinesis in facial palsy sequelae. Repeated injections are necessary and permanent improvements have been reported. We objectively evaluated the changes in synkinesis at >6 months after BTX-A injection, including changes over time with the number of administrations. METHODS: In 48 patients who received multiple BTX-A injections, evaluation by the Sunnybrook Facial Grading System (FGS) and integrated electromyography (iEMG) was performed before treatment and at least 6 months after the first, second, and third BTX-A injection. The iEMG ratio on the affected and healthy sides was calculated for each mimetic muscle and mimic motion. RESULTS: There was no significant difference in the FGS synkinesis score before treatment and after the third injection, although an improvement was observed. The iEMG ratio was significantly improved in the orbicularis oculi with open-mouth smile and lip pucker after the third dose compared to before treatment. The orbicularis oris showed a significant improvement when the eyelids were closed, while the platysma showed a significant improvement when the eyelids were closed and when the lip was pursed. Multiple regression analysis revealed that the orbicularis oculi and platysma had a greater effect on the iEMG ratio for the number of treatments than other factors. CONCLUSIONS: Repeated BTX-A injections showed improvements in synkinesis for the orbicularis oculi, orbicularis oris, and platysma, even after >6 months, compared to before treatment.

Room-temperature quantum coherence of entangled multiexcitons in a metal-organic framework.

Singlet fission can generate an exchange-coupled quintet triplet pair state 5TT, which could lead to the realization of quantum computing and quantum sensing using entangled multiple qubits even at room temperature. However, the observation of the quantum coherence of 5TT has been limited to cryogenic temperatures, and the fundamental question is what kind of material design will enable its room-temperature quantum coherence. Here, we show that the quantum coherence of singlet fission-derived 5TT in a chromophore-integrated metal-organic framework can be over hundred nanoseconds at room temperature. The suppressed motion of the chromophores in ordered domains within the metal-organic framework leads to the enough fluctuation of the exchange interaction necessary for 5TT generation but, at the same time, does not cause severe 5TT decoherence. Furthermore, the phase and amplitude of quantum beating depend on the molecular motion, opening the way to room-temperature molecular quantum computing based on multiple quantum gate control.

CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor-Mutated Advanced Non-Small-Cell Lung Cancer.

PURPOSE: We report CNS efficacy of first-line osimertinib plus chemotherapy versus osimertinib monotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) from the phase III FLAURA2 study according to baseline CNS metastasis status. METHODS: Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients with baseline CNS metastases; scans were assessed by neuroradiologist CNS blinded independent central review (BICR). RESULTS: On the basis of baseline CNS BICR, 118 of 279 (combination) and 104 of 278 (monotherapy) randomly assigned patients had ≥one measurable and/or nonmeasurable CNS lesion and were included in the CNS full analysis set (cFAS); 40 of 118 and 38 of 104 had ≥one measurable target CNS lesion and were included in the post hoc CNS evaluable-for-response set (cEFR). In the cFAS, the hazard ratio (HR) for CNS progression or death was 0.58 (95% CI, 0.33 to 1.01). In patients without baseline CNS metastases, the HR for CNS progression or death was 0.67 (95% CI, 0.43 to 1.04). In the cFAS, CNS objective response rates (ORRs; 95% CI) were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78); 59% versus 43% had CNS complete response (CR). In the cEFR, CNS ORRs (95% CI) were 88% (73 to 96) versus 87% (72 to 96); 48% versus 16% had CNS CR. CONCLUSION: Osimertinib plus platinum-pemetrexed demonstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progression, irrespective of baseline CNS metastasis status. These data support this combination as a new first-line treatment for patients with EGFR-mutated advanced NSCLC, including those with CNS metastases.

Continuous Nanospace in Nanoporous Liquid Crystal Investigated by 129 Xe NMR Spectroscopy.

Continuous nanopores within fluid materials could be used for novel chemical events such as the accommodation of guest molecules, unique arrays of the entrapped molecules, and chemical reactions in a dynamic molecular assembly. Columnar liquid crystals composed of a one-dimensionally stacked assembly of shape-persistent macrocycles form nanochannels owing to the intrinsic nanospace in the column. However, the existence of substantial nanoporosity has not been confirmed experimentally thus far. In this study, for the first time in the literature, we confirmed the presence of discrete and spatiotemporally continuous voids in a liquid-crystalline material. In 129 Xe NMR spectroscopy of liquid crystalline columnar assembly of imine-bridged shape-persistent macrocycles under Xe atmosphere, the NMR signals of the Xe atoms entrapped in the liquid-crystalline macrocycle depended on the gas pressure and phase-transition temperatures. These results indicate that the encapsulation of Xe gas molecules within the discrete and oriented nanospaces of nanoporous liquid crystals is different from the homogeneous dissolution of the solute in an ordinary solution.

Calamitic Liquid Crystals for Reversible Light-Modulated Phase Regulation Based on Arylazopyrazole Photoswitches.

The design of responsive liquid crystals enables a diversity of technological applications. Especially photochromic liquid crystals gained a lot of interest in recent years due to the excellent spatiotemporal control of their phase transitions. In this work we present calamitic light responsive mesogens based on a library of arylazopyrazole photoswitches. These compounds show liquid-crystalline behavior as shown by differential scanning calorimetry, grazing incidence X-ray diffraction and polarized optical microscopy. UV-vis spectroscopy and NMR analysis confirmed the excellent photophysical properties in solution and thin film. Additionally, polarized optical microscopy studies of the pristine compounds show reversible phase transition upon irradiation with light. Moreover, as a dopant in the commercially available liquid crystal 4-cyano-4'-pentylbiphenyl (5CB), the temperature range was reduced to ambient temperatures while preserving the photophysical properties. Remarkably, this co-assembled system shows reversible liquid-crystalline to isotropic phase transition upon irradiation with light of different wavelengths. The spatiotemporal control of the phase transition of the liquid crystals offers opportunities in the development of optical devices.

Calamitic Liquid Crystals for Reversible Light-Modulated Phase Regulation Based on Arylazopyrazole Photoswitches.

Invited for the cover of this issue are the groups of Kentaro Tanaka at Nagoya University and Bart Jan Ravoo at the University of Münster. The image depicts the photoisomerization of a mesogen upon irradiation with different wavelengths of light. Read the full text of the article at 10.1002/chem.202302958.

A Phase 2 Single-Arm Study of Osimertinib for Radiotherapy-Naive Central Nervous System Metastasis NSCLC: Results for the First-Line Cohort of the OCEAN Study (LOGIK 1603/WJOG 9116L).

Introduction: Osimertinib may be effective in treating central nervous system (CNS) metastasis, but its efficacy in treating radiation therapy (RT)-naive metastasis is unclear. The OCEAN study assessed the efficacy of osimertinib against RT-naive CNS metastasis in patients previously treated (T790M cohort) and untreated patients (first-line cohort) with EGFR mutation. Here, we report the results of the first-line cohort. Methods: Previously untreated patients with RT-naive CNS metastasis and EGFR mutation-positive NSCLC were treated with osimertinib. The brain metastasis response rate (BMRR), progression-free survival (PFS), and overall survival in the first-line cohort were secondary end points. Results: A total of 26 patients were enrolled in the study between September 2019 and July 2020. The median age was 72.0 years with 80.8% female. There were 20 patients who had multiple CNS metastases. BMRR assessed by PAREXEL criteria was 76.9% (90% confidence interval [CI]: 63.3%-90.5%), BMRR assessed by Response Evaluation Criteria in Solid Tumors was 76.9% (95% CI: 54.0%-99.8%), and median PFS of CNS metastasis was 22.0 months (95% CI: 9.7 mo-not reached). The overall response rate was 64.0% (95% CI: 45.2%-82.8%), median PFS was 11.5 months (95% CI: 6.9 mo-not reached), and median survival time was 23.7 months (95% CI: 16.5 mo-not reached). Paronychia and increased creatinine level were the most frequent nonhematological toxicities observed in 13 patients (50%). Grade three and higher adverse events were less than 10%, and there were no treatment-related deaths. Pneumonitis was observed in five patients (19.2%). Conclusions: These results suggest that osimertinib is effective in untreated patients with RT-naive asymptomatic CNS metastasis in a clinical practice first-line setting. Trial registration: UMIN identifier: UMIN000024218. jRCT identifier: jRCTs071180017.

Randomized phase I/II study of vascular endothelial growth factor receptor peptide vaccines for patients with hepatocellular carcinoma.

AIM: We evaluated the safety and efficacy of vascular endothelial growth factor receptor (VEGFR)-targeted peptide vaccines for the immunization of patients with unresectable hepatocellular carcinoma (HCC) who had responded to transarterial chemoembolization. METHODS: Twenty-two patients were randomized 1:1 to receive VEGFR-targeted peptides or placebo. The primary end-point was the safety assessment of the immunization. The secondary end-points were evaluation of immunological responses and clinical outcomes. RESULTS: No severe adverse events were induced by the study agents. Among the 12 patients in the vaccine group, a VEGFR1-specific cytotoxic T lymphocyte (CTL) response was induced in eight (66.7%) patients and a VEGFR2-specific CTL response was induced in 10 (83.3%). The median progression-free survival (PFS) and overall survival (OS) rates were 4.8 and 52.0 months, respectively, in the vaccine group, and 2.7 and 21.8 months, respectively, in the placebo group. No statistically significant differences were found between the two groups (PFS p = 0.925, OS p = 0.190). When divided into two groups according to immunoreactivity, the median PFS of patients with and without a strong immune response to VEGFR1 were 7.4 and 2.7 months, and that to VEGFR2 were 10.6 and 2.7 months, respectively; there were significant differences according to the immune response. CONCLUSIONS: Immunotherapy with peptide vaccines targeting VEGFR1 and VEGFR2 was well tolerated with no serious adverse events. It also effectively induced peptide-specific CTLs in patients with unresectable HCC.

The use of tourniquet is useful in terms of blood loss and soft tissue damage in arthroscopic anterior cruciate ligament reconstruction: a retrospective study.

Whether a tourniquet should be used for anterior cruciate ligament reconstruction (ACLR) when the operative field is secured remains controversial. Little is known about the influence of not using a tourniquet on total perioperative blood loss and soft tissue damage. The aim of this study was to compare total perioperative blood loss and soft tissue damage with and without tourniquet use during ACLR. Seventy-seven consecutive ACLRs in 76 patients were performed without tourniquet use at our hospital and enrolled in this study (T- group) between November 2018 and September 2021. The control group (T + group) comprised 55 historical ACLRs in 55 patients performed with tourniquet use at our hospital between April 2017 and September 2018. Total perioperative blood loss, calculated from the change in hemoglobin between that preoperatively and on postoperative day (POD) 1, and indicators of soft tissue damage including serum white blood cell (WBC) counts, creatine phosphokinase (CPK), and C-reactive protein (CRP) values measured on POD 1 and POD 7 were compared between groups. Total blood loss was significantly higher in the T- group (339 ± 216 mL) than in the T + group (258 ± 199 mL; P = 0.030). On POD 1, WBC counts were significantly higher in the T- group (9.7 ± 2.4 × 103 cells/µL) than in the T + group (9.1 ± 2.5 × 103 cells/µL; P = 0.043), CPK levels were significantly higher in the T- group (294 ± 417 U/L) than in the T + group (255 ± 88 U/L; P = 0.046), and CRP levels were also significantly higher in the T- group (1.40 ± 1.12 mg/dL) than in the T + group (0.91 ± 0.76 mg/dL; P = 0.016). No significant differences in WBC counts or CPK or CRP levels were seen between groups on POD 7. Total blood loss and soft tissue damage were significantly increased without tourniquet use during ACLR. No advantage was found for not using a tourniquet in terms of blood loss or soft tissue damage.

Accessory fragment migration in a professional baseball player with bipartite patella: A case report.

INTRODUCTION: Bipartite patella (BP) is usually recognized as an incidental radiographic finding. Therefore, no reports have observed the process of accessory fragment migration. We present the case of a professional baseball pitcher with significant migration of the fragment during follow-up. PRESENTATION OF CASE: A 26-year-old man was diagnosed with symptomatic BP and underwent conservative therapy. Eleven months later, he was unable to play baseball because of gradually worsening knee pain without obvious trauma. On radiographs, the accessory fragment which had located at the superolateral pole 11 months earlier migrated posterolaterally. The diagnosis of Saupe's type III BP was established, and open excision of the accessory fragment was performed. Postoperatively, full-weight-bearing walking and range-of-motion exercises were started the day after surgery. Three months after surgery, he could pitch with all his power without pain. DISCUSSION: Since our patient was a professional baseball right-handed pitcher who needed to step strongly on his left knee during pitching, strong traction force from the vastus lateralis was likely to have been repeatedly applied to the accessory fragment. It might lead to migration of the accessory fragment. The open excision of the accessory fragment was performed because the accessory fragment had migrated away from the patella body. CONCLUSION: We report a case of professional baseball player with symptomatic BP, in which case the chronological migration of the accessory fragment was observed without obvious trauma. When the accessory fragment is identified without obvious trauma, one of the differential diseases could be a BP.

YAP mediates resistance to EGF-induced apoptosis in EGFR-mutated non-small cell lung cancer cells.

Mechanisms underlying the growth and survival of non-small cell lung cancer (NSCLC) cells positive for activating mutations of the epidermal growth factor receptor gene (EGFR) have remained unclear. We here examined the functional relation between such mutant forms of EGFR and Yes-associated protein (YAP), a transcriptional coactivator of the Hippo signaling pathway that regulates cell proliferation and survival. Under the condition of serum deprivation, epidermal growth factor (EGF) induced activation of YAP in NSCLC cell lines positive for mutated EGFR but not in those wild type (WT) for EGFR. Similar EGF-induced activation of YAP was apparent in A549 lung cancer cells forcibly expressing mutant EGFR but not in those overexpressing the WT receptor. Furthermore, EGF induced apoptotic cell death in serum-deprived A549 cells overexpressing the WT form of EGFR but not in those expressing mutant EGFR, and knockdown of YAP rendered the latter cells sensitive to this effect of EGF. Our results thus suggest that activation of YAP mediates resistance of EGFR-mutated NSCLC cells to EGF-induced apoptosis and thereby contributes specifically to the survival of such cells.

Pre-treatment methods for stable oxygen and carbon isotope analyses of structural carbonates of bones in marine teleost fishes.

RATIONALE: Although the proportion of structural carbonates in vertebrate bones is low, the values of isotopes, namely stable oxygen (δ18 O) and carbon (δ13 C), in structural carbonates provide environmental and physiological information, which can be beneficial for estimating the palaeontological and ecological parameters of vertebrates. However, a few studies have analysed the isotopes of structural carbonates in modern teleost fishes, and a well-developed protocol for sample preparation is lacking. METHODS: We examined different pre-treatment methods of preparing bone samples of three marine teleost fishes (Japanese flounder, Pacific bluefin tuna and yellowtail) and investigated the effects of the cleaning methods on the stable isotope values of structural carbonates among vertebrae in the same individual. Isotope values were analysed using isotope ratio mass spectrometry. RESULTS: Physical cleaning was the most promising pre-treatment method and resulted in δ18 O values that were comparable to those of otoliths. Chemical treatments with NaOH and H2 O2 changed the percentage of structural carbonates in the bone and affected δ18 O and δ13 C values. High-temperature treatments, such as boiling and roasting, altered δ18 O values due to the exchange of oxygen with environmental water or vapour. CONCLUSIONS: Our results suggest that chemical cleaning methods used to prepare bone phosphate or collagen samples for isotope analyses are not suitable for structural carbonates. Physical cleaning is the appropriate pre-treatment method for analysing the isotopes of structural carbonates. Also, we emphasise that standardising the vertebral number is necessary to make δ13 C values comparable between specimens in the same species.