Doping of molecular semiconductors through proton-coupled electron transfer.

The chemical doping of molecular semiconductors is based on electron-transfer reactions between the semiconductor and dopant molecules; here, the redox potential of the dopant is key to control the Fermi level of the semiconductor1,2. The tunability and reproducibility of chemical doping are limited by the availability of dopant materials and the effects of impurities such as water. Here we focused on proton-coupled electron-transfer (PCET) reactions, which are widely used in biochemical processes3,4; their redox potentials depend on an easily handled parameter, that is, proton activity. We immersed p-type organic semiconductor thin films in aqueous solutions with PCET-based redox pairs and hydrophobic molecular ions. Synergistic reactions of PCET and ion intercalation resulted in efficient chemical doping of crystalline organic semiconductor thin films under ambient conditions. In accordance with the Nernst equation, the Fermi levels of the semiconductors were controlled reproducibly with a high degree of precision-a thermal energy of about 25 millielectronvolts at room temperature and over a few hundred millielectronvolts around the band edge. A reference-electrode-free, resistive pH sensor based on this method is also proposed. A connection between semiconductor doping and proton activity, a widely used parameter in chemical and biochemical processes, may help create a platform for ambient semiconductor processes and biomolecular electronics.

Efficient molecular doping of polymeric semiconductors driven by anion exchange.

The efficiency with which polymeric semiconductors can be chemically doped-and the charge carrier densities that can thereby be achieved-is determined primarily by the electrochemical redox potential between the π-conjugated polymer and the dopant species1,2. Thus, matching the electron affinity of one with the ionization potential of the other can allow effective doping3,4. Here we describe a different process-which we term 'anion exchange'-that might offer improved doping levels. This process is mediated by an ionic liquid solvent and can be pictured as the effective instantaneous exchange of a conventional small p-type dopant anion with a second anion provided by an ionic liquid. The introduction of optimized ionic salt (the ionic liquid solvent) into a conventional binary donor-acceptor system can overcome the redox potential limitations described by Marcus theory5, and allows an anion-exchange efficiency of nearly 100 per cent. As a result, doping levels of up to almost one charge per monomer unit can be achieved. This demonstration of increased doping levels, increased stability and excellent transport properties shows that anion-exchange doping, which can use an almost infinite selection of ionic salts, could be a powerful tool for the realization of advanced molecular electronics.

Mechanism of ERBB2 gene overexpression by the formation of super-enhancer with genomic structural abnormalities in lung adenocarcinoma without clinically actionable genetic alterations.

BACKGROUND: In an extensive genomic analysis of lung adenocarcinomas (LUADs), driver mutations have been recognized as potential targets for molecular therapy. However, there remain cases where target genes are not identified. Super-enhancers and structural variants are frequently identified in several hundred loci per case. Despite this, most cancer research has approached the analysis of these data sets separately, without merging and comparing the data, and there are no examples of integrated analysis in LUAD. METHODS: We performed an integrated analysis of super-enhancers and structural variants in a cohort of 174 LUAD cases that lacked clinically actionable genetic alterations. To achieve this, we conducted both WGS and H3K27Ac ChIP-seq analyses using samples with driver gene mutations and those without, allowing for a comprehensive investigation of the potential roles of super-enhancer in LUAD cases. RESULTS: We demonstrate that most genes situated in these overlapped regions were associated with known and previously unknown driver genes and aberrant expression resulting from the formation of super-enhancers accompanied by genomic structural abnormalities. Hi-C and long-read sequencing data further corroborated this insight. When we employed CRISPR-Cas9 to induce structural abnormalities that mimicked cases with outlier ERBB2 gene expression, we observed an elevation in ERBB2 expression. These abnormalities are associated with a higher risk of recurrence after surgery, irrespective of the presence or absence of driver mutations. CONCLUSIONS: Our findings suggest that aberrant gene expression linked to structural polymorphisms can significantly impact personalized cancer treatment by facilitating the identification of driver mutations and prognostic factors, contributing to a more comprehensive understanding of LUAD pathogenesis.

Molecular subtypes of lung adenocarcinoma present distinct immune tumor microenvironments.

Overcoming resistance to immune checkpoint inhibitors is an important issue in patients with non-small-cell lung cancer (NSCLC). Transcriptome analysis shows that adenocarcinoma can be divided into three molecular subtypes: terminal respiratory unit (TRU), proximal proliferative (PP), and proximal inflammatory (PI), and squamous cell carcinoma (LUSQ) into four. However, the immunological characteristics of these subtypes are not fully understood. In this study, we investigated the immune landscape of NSCLC tissues in molecular subtypes using a multi-omics dataset, including tumor-infiltrating leukocytes (TILs) analyzed using flow cytometry, RNA sequences, whole exome sequences, metabolomic analysis, and clinicopathologic findings. In the PI subtype, the number of TILs increased and the immune response in the tumor microenvironment (TME) was activated, as indicated by high levels of tertiary lymphoid structures, and high cytotoxic marker levels. Patient prognosis was worse in the PP subtype than in other adenocarcinoma subtypes. Glucose transporter 1 (GLUT1) expression levels were upregulated and lactate accumulated in the TME of the PP subtype. This could lead to the formation of an immunosuppressive TME, including the inactivation of antigen-presenting cells. The TRU subtype had low biological malignancy and "cold" tumor-immune phenotypes. Squamous cell carcinoma (LUSQ) did not show distinct immunological characteristics in its respective subtypes. Elucidation of the immune characteristics of molecular subtypes could lead to the development of personalized immune therapy for lung cancer. Immune checkpoint inhibitors could be an effective treatment for the PI subtype. Glycolysis is a potential target for converting an immunosuppressive TME into an antitumorigenic TME in the PP subtype.

Clinical and Pathologic Differences between Small-Cell Carcinoma and Large-Cell Neuroendocrine Carcinoma of the Lung.

BACKGROUND: Both small-cell carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC) of the lung are often clinically dealt with as being in the same category as neuroendocrine carcinoma, and their clinical differences have not been adequately assessed. METHODS: The postoperative prognosis was retrospectively analyzed using the data of 196 patients who underwent resection for SCLC or LCNEC. RESULTS: Of the patients included, 99 (50.5%) had SCLC and 97 (49.5%) had LCNEC. The median duration of follow-up was 39 months (interquartile range [IQR] 21-76) and 56 months (IQR 21-87) for SCLC and LCNEC, respectively. The estimated 5-year overall survival (OS) probabilities were 53.7% and 62.7% (p = 0.133) for patients with SCLC and LCNEC, respectively. In the SCLC group, a multivariate analysis showed that adjuvant chemotherapy (hazard ratio 0.54, 95% confidence interval 0.30-0.99, p = 0.04) was the only factor that was significantly associated with OS. In the LCNEC group, univariate analyses demonstrated that pathologic stage I (p = 0.01) was the only factor that was associated with better OS after surgery. CONCLUSIONS: We found different clinical features in SCLC and LCNEC; in patients with SCLC, because OS could be expected to significantly improve with postoperative adjuvant chemotherapy, patients with resected SCLC of any pathologic stage should receive adjuvant chemotherapy. For patients with LCNEC, because pathologic stage I LCNEC is related to better prognosis than any other stages, a thorough clinical staging, including invasive staging, according to present guidelines should be performed to identify clinical stage I LCNEC with the highest certainty.

Impact of 18F-FDG PET on TNM Staging and Prognosis in Thymic Epithelial Tumors.

BACKGROUND: Preoperative fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) of thymic epithelial tumors (TETs) is well known for identifying malignant-grade TETs; however, its predictive power for determining locally advanced tumors, lymph node (LN) metastasis, and prognosis remains unknown. PATIENTS AND METHODS: We retrospectively evaluated patients with resectable TETs who were preoperatively assessed using 18F-FDG PET from January 2012 to January 2023. The receiver operating characteristic curve was used to evaluate the cutoff value of the maximum standardized uptake value (SUVmax) to predict advanced-stage disease. Recurrence/progression-free survival (RFS/PFS) was analyzed using the Kaplan-Meier method. The staging was classified according to the tumor-node-metastasis system. RESULTS: Our study included 177 patients; 145 (81.9%) had pathological early-stage TET (stage I or II), and 32 (19.1%) had advanced stage (stage III or IV). The area under the curve value for predicting the advanced stage was 0.903, and the cutoff value was 5.6 (sensitivity 81.3%, specificity 84.8%). SUVmax > 5.6 was associated with worse prognosis for RFS/PFS. LN metastasis was preoperatively detected by FDG uptake in 30.8% of patients with pathological LN positivity, whereas LN metastasis was not pathologically detected in patients with SUVmax < 5.9. In patients with advanced-stage TETs, LN recurrence was more frequent in patients who were preoperatively detected by 18F-FDG PET than those who were not (75.0% versus 7.1%). CONCLUSIONS: 18F-FDG PET is a potentially valuable tool for predicting advanced stage and poor prognosis of recurrence in patients with TETs. SUVmax can help thoracic surgeons to guide them in selecting appropriate therapeutic strategies for TETs.

A randomized phase III trial of postoperative surveillance for pathological stage II and IIIA non-small cell lung cancer (JCOG2012, PHOENIX).

The goal of postoperative surveillance following non-small cell lung cancer surgery is to detect recurrence and second primary malignancies while curative treatment is still possible. Although several guidelines recommend that patients have computed tomography (CT) scans every 6 months for the first 2 years after resection, then once a year, there is no evidence that it is effective for survival, especially in locally advanced non-small cell lung cancer. In October 2022, we launched a multi-institutional, randomized controlled phase III trial for pathological stage II and IIIA non-small cell lung cancer patients to confirm the non-inferiority of less intensive surveillance with less frequent CT scans versus standard surveillance in terms of overall survival. The primary endpoint is overall survival. We intend to enroll 1100 patients from 45 institutions over 4 years. The trial has been registered in the Japan Registry of Clinical Trials under the code jRCT1030220361 (https://jrct.niph.go.jp/latest-detail/jRCT1030220361).

Rare but clinically important salivary gland-type tumor of the lung: A review.

Salivary gland-type tumor (SGT) of the lung, which arises from the bronchial glands of the tracheobronchial tree, was first recognized in the 1950s. SGT represents less than 1% of all lung tumors and is generally reported to have a good prognosis. Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are the two most common subtypes, comprising more than 90% of all SGTs. The reported 5-year survival rate of patients with SGT is 63.4%. Because this type of tumor develops in major bronchi, patients with SGT commonly present with symptoms of bronchial obstruction, including dyspnea, shortness of breath, wheezing, and coughing; thus, the tumor is usually identified at an early stage. Most patients are treated by lobectomy and pneumonectomy, but bronchoplasty or tracheoplasty is often needed to preserve respiratory function. Lymphadenectomy in the surgical resection of SGT is recommended, given that clinical benefit from lymphadenectomy has been reported in patients with MEC. For advanced tumors, appropriate therapy should be considered according to the subtype because of the varying clinicopathologic features. MEC, but not ACC, is less likely to be treated with radiation therapy because of its low response rate. Although previous researchers have learned much from studying SGT over the years, the diagnosis and treatment of SGT remains a complex and challenging problem for thoracic surgeons. In this article, we review the diagnosis, prognosis, and treatment (surgery, chemotherapy, and radiotherapy) of SGT, mainly focusing on MEC and ACC. We also summarize reports of adjuvant and definitive radiation therapy for ACC in the literature.

Clinical outcomes of left upper segmentectomy vs. lobectomy for early non-small-cell lung cancer: a nationwide database study in Japan.

PURPOSE: Given that left upper lobe and right upper and middle lobes share a similar anatomy, segmentectomy, such as upper division and lingulectomy, should yield identical oncological clearance to left upper lobectomy. We compared the prognosis of segmentectomy with that of lobectomy for early stage non-small-cell lung cancer (NSCLC) in the left upper lobe. METHODS: We retrospectively examined 2115 patients who underwent segmentectomy or lobectomy for c-stage I (TNM 8th edition) NSCLC in the left upper lobe in 2010. We compared the oncological outcomes of segmentectomy (n = 483) and lobectomy (n = 483) using a propensity score matching analysis. RESULTS: The 5-year recurrence-free and overall survival rates in the segmentectomy and lobectomy groups were comparable, irrespective of c-stage IA or IB. Subset analyses according to radiological tumor findings showed that segmentectomy yielded oncological outcomes comparable to those of lobectomy for non-pure solid tumors. In cases where the solid tumor exceeded 20 mm, segmentectomy showed a recurrence-free survival inferior to that of lobectomy (p = 0.028), despite an equivalent overall survival (p = 0.38). CONCLUSION: Segmentectomy may be an acceptable alternative to lobectomy with regard to the overall survival of patients with c-stage I NSCLC in the left upper lobe.

Quantitative identification of causes of instrumental acoustic signal distortion in Global Navigation Satellite System-Acoustics Combination observations.

The Seafloor Geodetic Observation-Array (SGO-A), operated by the Japan Coast Guard, relies on the Global Navigation Satellite System-Acoustics combination (GNSS-A) technique, which integrates satellite positioning systems and undersea acoustic ranging to determine seafloor crustal deformation at the centimeter level for earthquake disaster prevention. Recently, we found distortion in the SGO-A 10-kHz carrier wave that degraded the accuracy. Carrier wave distortion can cause errors on the scale of several centimeters to twenty centimeters, which greatly impedes centimeter-level observations. This study investigated this carrier wave degradation by an underwater acoustic communication experiment conducted in 2022, using a transducer similar to that used by SGO-A. Also, we reproduced degraded waveforms through a grid search-like method for quantitatively evaluating the extent to which the interior of the equipment contributed to deterioration. Our results underscore the importance of careful consideration in signal processing, as the observed waveform degradation is not solely attributed to hardware structures but also to internal electrical circuits. The findings suggest that conventional signal identification methods may lead to errors, providing motivation for a shift towards experimental and experiential timing-based waveform identification approaches to enhance accuracy in GNSS-A systems.

Larger yellow-phase Japanese eels show short-range homing in a freshwater river.

The homing behavior and site fidelity to habitats in various fishes, including anguillid eels (genus Anguilla), are fascinating. However, little is known about how yellow-phase eels exhibit homing behavior and the sensory mechanisms involved. Using acoustic telemetry, we investigated the homing behavior of 18 Japanese eels, A. japonica, with total lengths ranging from 204 to 570 mm, in a narrow freshwater river in inland central Japan, where salinity gradient, tidal current, and magnetic sense cannot be used for their homing, but where olfaction could play a role. The tagged eels captured upstream and downstream were released downstream and upstream, respectively. The results showed that large eels, over approximately 400 mm in total length, exhibited homing behavior to their original sampling locations (likely to shelters and foraging sites, where they probably spent a longer time than in other locations and grew successfully) from outside their home ranges, predominantly during the dark period. Homing success was not affected by the two capture locations, indicating that eels did not use olfactory cues for short-range homing in freshwater rivers.

[Transurethral Resection of Necrotic Tissue in the Bladder Caused by Emphysematous Cystitis].

Emphysematous cystitis is a relatively rare form of urinary tract infection. A 72-year-old man with diabetes mellitus and long-term indwelling urethral catheterization was diagnosed with emphysematous cystitis. The clinical findings were resolved by conservatively managing the patient with antibiotics. However, cystoscopy subsequently revealed a yellowish-white soft tissue mass in the bladder, which was unlikely to be a bladder tumor. The mass could not be removed easily and frequently caused urinary catheter obstruction. We successfully removed this mass by performing transurethral resection twice. Through histopathological examination, the mass was identified as necrotic tissue comprising bacteria, fibrin, and suspected bladder mucosa.

Sulfatide-selectin signaling in the spinal cord induces mechanical allodynia.

Sulfatide is a sulfated glycosphingolipid that is present abundantly in myelin sheaths of the brain and spinal cord. It is synthesized by a cerebroside sulfotransferase encoded by Gal3st1, which catalyzes the transfer of sulfate from 3'-phosphoadenylylsulfate to galactosylceramide. We previously reported that Gal3st1 gene expression in the spinal cord is up-regulated 1 day after intraplantar injection of complete Freund's adjuvant (CFA), indicating that sulfatide is involved in inflammatory pain. In the present study, we found that intrathecal injection of sulfatide led to mechanical allodynia. Sulfatide caused levels of glial fibrillary acidic protein (GFAP) and nitric oxide in the spinal cord to increase. Mechanical allodynia induced by intrathecal injection of sulfatide was blocked by nitric oxide synthase inhibitors and by suppression of astrocyte activation by L-α-aminoadipate. These results suggest that sulfatide-induced mechanical allodynia involved glial activation and nitric oxide production. Blocking selectin, a sulfatide-binding protein, with bimosiamose attenuated sulfatide-induced allodynia and ameliorated CFA-induced mechanical allodynia during inflammatory pain. Finally, elevated levels of sulfatide concentration in the spinal cord were observed during CFA-induced inflammatory pain. The elevated sulfatide levels enhanced selectin activation in the spinal cord, resulting in mechanical allodynia. Our data suggest that sulfatide-selectin interaction plays a key role in inflammatory pain.

Tumor microenvironment-mediated immune profiles and efficacy of anti-PD-L1 antibody plus chemotherapy stratified by DLL3 expression in small-cell lung cancer.

BACKGROUND: Delta-like ligand 3 (DLL3) is a therapeutic target in small-cell lung cancer (SCLC). However, how DLL3 expression status affects the tumor microenvironment (TME) and clinical outcomes in SCLC remains unclear. METHODS: This retrospective study included patients with postoperative limited-stage (LS)-SCLC and extensive-stage (ES)-SCLC treated with platinum and etoposide (PE) plus anti-programmed cell death ligand 1 (PD-L1) antibody. We investigated the relationship of DLL3 expression with TME, mutation status, tumor neoantigens, and immunochemotherapy. RESULTS: In the LS-SCLC cohort (n = 59), whole-exome sequencing revealed that DLL3High cases had significantly more neoantigens (P = 0.004) and a significantly higher rate of the signature SBS4 associated with smoking (P = 0.02) than DLL3Low cases. Transcriptome analysis in the LS-SCLC cohort revealed that DLL3High cases had significantly suppressed immune-related pathways and dendritic cell (DC) function. SCLC with DLL3High had significantly lower proportions of T cells, macrophages, and DCs than those with DLL3Low. In the ES-SCLC cohort (n = 30), the progression-free survival associated with PE plus anti-PD-L1 antibody was significantly worse in DLL3High cases than in DLL3Low cases (4.7 vs. 7.4 months, P = 0.01). CONCLUSIONS: Although SCLC with DLL3High had a higher neoantigen load, these tumors were resistant to immunochemotherapy due to suppressed tumor immunity by inhibiting antigen-presenting functions.

Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial.

BACKGROUND: Lobectomy is the standard of care for early-stage non-small-cell lung cancer (NSCLC). The survival and clinical benefits of segmentectomy have not been investigated in a randomised trial setting. We aimed to investigate if segmentectomy was non-inferior to lobectomy in patients with small-sized peripheral NSCLC. METHODS: We conducted this randomised, controlled, non-inferiority trial at 70 institutions in Japan. Patients with clinical stage IA NSCLC (tumour diameter ≤2 cm; consolidation-to-tumour ratio >0·5) were randomly assigned 1:1 to receive either lobectomy or segmentectomy. Randomisation was done via the minimisation method, with balancing for the institution, histological type, sex, age, and thin-section CT findings. Treatment allocation was not concealed from investigators and patients. The primary endpoint was overall survival for all randomly assigned patients. The secondary endpoints were postoperative respiratory function (6 months and 12 months), relapse-free survival, proportion of local relapse, adverse events, proportion of segmentectomy completion, duration of hospital stay, duration of chest tube placement, duration of surgery, amount of blood loss, and the number of automatic surgical staples used. Overall survival was analysed on an intention-to-treat basis with a non-inferiority margin of 1·54 for the upper limit of the 95% CI of the hazard ratio (HR) and estimated using a stratified Cox regression model. This study is registered with UMIN Clinical Trials Registry, UMIN000002317. FINDINGS: Between Aug, 10, 2009, and Oct 21, 2014, 1106 patients (intention-to-treat population) were enrolled to receive lobectomy (n=554) or segmentectomy (n=552). Patient baseline clinicopathological factors were well balanced between the groups. In the segmentectomy group, 22 patients were switched to lobectomies and one patient received wide wedge resection. At a median follow-up of 7·3 years (range 0·0-10·9), the 5-year overall survival was 94·3% (92·1-96·0) for segmentectomy and 91·1% for lobectomy (95% CI 88·4-93·2); superiority and non-inferiority in overall survival were confirmed using a stratified Cox regression model (HR 0·663; 95% CI 0·474-0·927; one-sided p<0·0001 for non-inferiority; p=0·0082 for superiority). Improved overall survival was observed consistently across all predefined subgroups in the segmentectomy group. At 1 year follow-up, the significant difference in the reduction of median forced expiratory volume in 1 sec between the two groups was 3·5% (p<0·0001), which did not reach the predefined threshold for clinical significance of 10%. The 5-year relapse-free survival was 88·0% (95% CI 85·0-90·4) for segmentectomy and 87·9% (84·8-90·3) for lobectomy (HR 0·998; 95% CI 0·753-1·323; p=0·9889). The proportions of patients with local relapse were 10·5% for segmentectomy and 5·4% for lobectomy (p=0·0018). 52 (63%) of 83 patients and 27 (47%) of 58 patients died of other diseases after lobectomy and segmentectomy, respectively. No 30-day or 90-day mortality was observed. One or more postoperative complications of grade 2 or worse occurred at similar frequencies in both groups (142 [26%] patients who received lobectomy, 148 [27%] who received segmentectomy). INTERPRETATION: To our knowledge, this study was the first phase 3 trial to show the benefits of segmentectomy versus lobectomy in overall survival of patients with small-peripheral NSCLC. The findings suggest that segmentectomy should be the standard surgical procedure for this population of patients. FUNDING: National Cancer Center Research and the Ministry of Health, Labour, and Welfare of Japan.

Long-Term Prognosis and Prognostic Indicators of Stage IA Lung Adenocarcinoma.

BACKGROUND: The 8th edition of the TNM stage classification of lung cancer was developed based on an evaluation of the 5-year prognosis using an international database. Since recurrence after 5 years postoperatively is known to develop, the applicability of the stage classification beyond 5 years after treatment needs to be evaluated. PATIENTS AND METHODS: Postoperative prognosis and prognostic indicators were analyzed using data for 648 patients of pathological stage IA adenocarcinoma, who underwent complete resection between 2007 and 2012. RESULTS: The median age was 66 years (interquartile range 60-73 years), and the median follow-up duration was 100 months (interquartile range 70-116 months). Overall survival probabilities for pathological stage IA1, IA2, and IA3 patients were 100%, 96.3%, and 91.5% at 5 postoperative years, and 94.2%, 89.8%, and 83.5% at 10 postoperative years, respectively (IA1 vs IA2: p = 0.05; IA2 vs IA3: p = 0.05). Multivariate analysis for overall survival of patients who survived without recurrence for 5 postoperative years revealed that age (hazard ratio 3.21, p = 0.02) was the only factor that was significantly associated with long-term survival. Stage classification (IA1, IA2, or IA3) was not an associated factor. The incidence of secondary primary lung cancer continued to increase, resulting in an estimated probability of 8.6% at 10 postoperative years. CONCLUSIONS: For patients who survived without recurrence for 5 postoperative years, age, not stage classification, was associated with survival thereafter. The long-term follow-up strategy does not need to be modified according to the stage classification, and screening for secondary primary lung cancer should be considered.

Nitrogen-Containing Perylene Diimides: Molecular Design, Robust Aggregated Structures, and Advances in n-Type Organic Semiconductors.

ConspectusOrganic semiconductors (OSCs) have attracted much attention because of their potential applications for flexible and printed electronic devices and thus have been extensively investigated in a variety of research fields, such as organic chemistry, solid-state physics, and device physics and engineering. Organic thin-film transistors (OTFTs), a class of OSC-based devices, have been expected to be an alternative of silicon-based metal oxide semiconductor field-effect transistors (MOSFETs), which is the indispensable element for most of the current electronic devices. However, the noncovalently aggregated, van der Waals solid nature of the OSCs, by contrast to covalently bound silicon, conventionally exhibits lower carrier mobilities, limiting the practical applications of OTFTs. In particular, electron-transporting (i.e., n-type) OSCs lag behind their hole-transporting (p-type) counterparts in carrier mobility and ambient stability as OTFTs. This is primarily because of the difficulty in achieving compatibility between the aggregated structure exhibiting excellent carrier mobility and that with enough electron affinity. Recent understandings of carrier transport in OSCs explain that large and two-dimensionally isotropic transfer integrals coupled with small fluctuations are crucial for high carrier mobilities. In addition, from a practical point of view, the compatibility with practical device processes is highly required. Rational molecular design principles, therefore, are still demanded for developing OSCs and OTFTs toward high-end device applications.Herein, we will show our recent progress in the development of n-type OSCs with the key π-electron core (π-core) of benzo[de]isoquinolino[1,8-gh]quinolinetetracarboxylic diimide (BQQDI) on the basis of single-crystal OTFT technologies and the band-transport model enabled by two-dimensional molecular packing arrangements. The critical point is the introduction of electronegative nitrogen atoms into the π-core: the nitrogen atoms in BQQDI not only deepen the molecular orbital energies but also allow hydrogen-bonding-like attractive intermolecular interactions to control the aggregated structures, unlike the conventional role of the nitrogen introduced into OSCs only for the former role. Hence, the BQQDI analogues exhibit air-stable OTFT behavior and two-dimensional brickwork packing structures. Specifically, phenethyl-substituted analogue (PhC2-BQQDI) has been shown as the first principal BQQDI-based material, demonstrating solution-processable thin-film single crystals, fewer anisotropic transfer integrals, and an effective suppression of molecular motions, leading to band-like electron-transport properties and stress-durable n-channel OTFT performances, in conjunction with the support of computational calculations. Insights into more fundamental points of view have been found by side-chain derivatization and OTFT studies on polycrystalline and single-crystal films. We hope that this Account provides readers with new strategies for designing high-performance OSCs by two-dimensional control of the aggregated structures.

Dynamics of recurrence after curative resection of nonsmall cell lung cancer.

BACKGROUND AND OBJECTIVES: This study examined the trend of hazards for postoperative recurrence of lung cancer according to pathologic stages. METHODS: We reviewed the records of 1987 patients who underwent resection for lung cancer between 2007 and 2012. Postoperative recurrence and development of second primary lung cancer were analyzed to evaluate the trend of hazard rate. RESULTS: Recurrence-free survival (RFS) probabilities at 5 postoperative years in patients with stage I/II/III disease were 87.8%/54.7%,/33.4%, respectively. The hazard rate of RFS was consistently low (<0.005) for stage I patients for 5 years after surgery. The hazard rate of RFS for stage II patients showed a peak of 0.016 at 12.4 months after surgery, and that for stage III patients had a higher peak of 0.029 at 13.7 months after surgery, after which they showed a gradual decrease. The hazard rate for the development of second primary lung cancer exceeded that of recurrence of first primary lung cancer after 72 months postoperatively. CONCLUSIONS: Short-interval postoperative surveillance might be unnecessary for stage I patients but should be considered in stage II/III patients. Screening of second primary lung cancer rather than surveillance of recurrence might be beneficial after more than 6 years postoperatively.

Features of anaplastic lymphoma kinase rearrangement in early-stage lung cancer: Analysis of a nationwide Japanese database.

BACKGROUND AND OBJECTIVES: Anaplastic lymphoma kinase (ALK) rearrangement is a representative driver mutation in lung cancer. However, the biology of early-stage ALK-rearranged lung cancer remains unclear. We aimed to assess the clinicopathological features, prognostic implications, and influence of ALK rearrangement on the postoperative course in surgically resected lung cancer. METHODS: We retrospectively analyzed data from the Japanese Joint Committee of Lung Cancer Registry database. Of the 12 730 patients with lung adenocarcinoma, 794 (6.2%) were tested for ALK rearrangement and were included. RESULTS: ALK rearrangements were detected in 76 patients (10%). The 5-year overall survival (OS) rate was significantly higher in the ALK rearrangement-positive group than in the ALK rearrangement-negative group (p = 0.030). Multivariable analysis revealed that ALK rearrangement was an independent prognostic factor for improved OS (hazard ratio, 0.521; 95% confidence interval, 0.298-0.911; p = 0.022). Regarding the postrecurrence state, there was no difference in the initial recurrence sites between both groups. Administration of ALK-tyrosine kinase inhibitors (TKIs) improved postrecurrence survival in any treatment lines. CONCLUSION: In one of the largest national surveys, ALK rearrangement was associated with improved long-term outcomes in surgically resected patients. ALK-TKIs may be an important treatment strategy for ALK rearrangement-positive lung adenocarcinoma in the postrecurrence state.

Individual and synergetic charge transport properties at the solid and electrolyte interfaces of a single ultrathin single crystal of organic semiconductors.

The chemical structures and morphologies of organic semiconductors (OSCs) and gate dielectrics have been widely investigated to improve the electrical performances of organic thin-film transistors (OTFTs) because the charge transport therein is a phenomenon at the semiconductor-dielectric interfaces. Here, solid and ionic gel gate dielectrics were adopted on the lower and upper surfaces, respectively, of a single, two molecule-thick single crystals of p-type OSCs to study the charge transport properties at individual interfaces between the morphologically compatible OSC surface and different gate dielectrics. Using the four-probe method, the solid and ionic gel interfaces were found to exhibit hole mobilities of 9.3 and 2.2 cm2 V-1 s-1, respectively, which revealed the crucial impact of the gate dielectric materials on the interfacial charge transport. Interestingly, when gate biases are applied through both dielectrics, i.e., under the solid/ionic gel dual-gate transistor operation, the hole mobility at the solid gate interface is improved up to 14.7 cm2 V-1 s-1, which is 1.5 times greater than that assessed without the ionic gel gate. This improvement can be attributed to the electric double layer formed at the ionic gel/uniform crystal surface, which provides a close-to-ideal charge transport interface through dramatic trap-filling. Therefore, the present dual-gate transistor technique will be promising for investigating the intrinsic charge-transport capabilities of OSCs.