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Abstract Background The AmoyDx Pan lung cancer PCR panel (AmoyDx PLC panel) has been approved as a companion diagnostic tool for multiple anticancer agents in patients with non‐small cell lung cancer (NSCLC). However, the suitability of cytology specimens as samples for the AmoyDx PLC panel remains unclear. We evaluated the performance of frozen cell pellets from cytology specimens (FCPs) in the Amoy 9‐in‐1 assay, a preapproval assay of the AmoyDx PLC panel. Methods We retrospectively collected data of NSCLC patients enrolled in LC‐SCRUM‐Asia from the Shizuoka Cancer Center between September 2019 and May 2021. Results A total of 49 cases submitted FCPs for evaluation of oncogenic driver alterations and were assessed using Amoy 9‐in‐1 and next‐generation sequencing (NGS) assays. The success rates of DNA and RNA analyses using the Amoy 9‐in‐1 were both 100%, compared with 86% and 45%, respectively, using NGS assays. Oncogenic driver alterations were detected in 27 (55%) and 23 (47%) patients using Amoy 9‐in‐1 and NGS, respectively. No inconsistent results were observed among 19 cases in which both assays showed successful detection. In the remaining 30 cases, 10 had inconsistent results: nine oncogenic driver alterations (3 MET, 2 ALK, 2 ROS1, and 2 KRAS) were detectable only in Amoy 9‐in‐1, and one epidermal growth factor receptor (EGFR) mutation was detectable only in NGS. Conclusion FCPs can be successfully used in the AmoyDx PLC panel, with higher success rate compared with the NGS assay. The AmoyDx PLC panel may be an option in cases when insufficient tissue sample is available for the NGS assay.

Abstract The possibility of stratifying patients according to differences in ROS proto‐oncogene 1 (ROS1) fusion partners has been discussed. This study aimed to clarify the clinicopathological differences between two SDC4::ROS1 positive NSCLC cases who had different responses to crizotinib. Cytology and pathology samples from two NSCLC cases with SDC4::ROS1 who were diagnosed and treated with crizotinib at Nihon University Itabashi Hospital were obtained. Case 1 has been well‐controlled with crizotinib for over 5 years, but case 2 was worse and overall survival was 19 months. Sequencing analysis of ROS1 fusion genes was performed by reverse‐transcription‐PCR and Sanger's sequencing methods. In addition, thyroid transcription factor (TTF)‐1, ROS‐1, Ki67, and phosphorylated extracellular signal‐regulated kinase (pERK)1/2 expression were investigated using immunohistochemistry. Sequencing analysis showed SDC4 exon2::ROS1 exon 32 (exon33 deleted) in case 1, and coexistence of SDC4 exon2::ROS1 exon 34 and SDC4 exon2::ROS1 exon35 in case 2. The Ki67 index was not different, but ROS1 and pERK1/2 expression levels tended to be higher in the tumor cells of case 2 than in case 1. Therapeutic response to crizotinib and patients' prognosis in ROS1 rearranged NSCLC may be related to the activation of ROS1 signaling, depending on ROS1 and pERK1/2 overexpression status, even if the ROS1 fusion partner is the same.

Abstract Background Anti-aminoacyl-tRNA synthetase (ARS) antibody-positive patients present with a variety of symptoms, including interstitial lung disease (ILD), which is termed anti-synthetase syndrome (ASS). But it is rare that ASS-ILD is considered an immune-related adverse event after the use of immune checkpoint inhibitors (ICIs). Case presentation A 47-year-old male with advanced lung adenocarcinoma was treated with platinum and ICI combination immunotherapy and was followed up as an outpatient. Nine months after the start of treatment, he developed a fever and cough, and imaging findings showed lung consolidations in the bilateral lower lung fields. The patient was positive for anti- ARS antibodies and was considered to have developed ASS-ILD due to ICIs remitted with steroid therapy. The patient was found to be positive for anti-ARS antibodies before ICI administration, and the antibody titer was elevated compared to that before ICI administration. Conclusions The examination of anti-ARS antibodies pior to the administration of ICIs may be useful in predicting the development of ASS-ILD.

Abstract Carboplatin plus etoposide is a standard treatment for older extensive‐stage small‐cell lung cancer (ES‐SCLC) patients with performance status (PS) 2. However, older patients often exhibit poor PS (3, 4), and the treatment effect in them is poorly understood. To determine the therapeutic efficacy and safety of carboplatin plus etoposide therapy for this population, we retrospectively analyzed 63 patients with ES‐SCLC with PS ≥2, aged ≥71 years, who had received first‐line carboplatin plus etoposide therapy. We compared the treatment efficacy and safety in patients with baseline PS 2 versus those with PS 3–4. In the PS 2 (38 patients) and PS ≥3 (25 patients) groups, the overall response rate was 71.1% and 72.0%, median progression‐free survival was 4.6 and 3.1 months, and overall survival was 7.7 and 5.1 months, respectively. PS improved to 0–1 post‐treatment in 65.8% and 48.0% of the patients in the PS 2 and PS ≥3 groups, respectively. Patients with PS ≥3 showing improved PS had a progression‐free survival of 6.1 months. A higher incidence of grade ≥3 decreased neutrophil counts, febrile neutropenia, and treatment‐related death was observed in the PS ≥3 group. The progression‐free survival of patients administered prophylactic granulocyte colony‐stimulating factor (G‐CSF) was 5.2 and 6.1 months in the PS2 and PS ≥3 groups. Overall, carboplatin plus etoposide therapy provided comparable tumor shrinkage, but shorter progression‐free and overall survival in older ES‐SCLC patients with PS ≥3 than in those with PS 2. Thus, supportive care, such as prophylactic G‐CSF administration, may be necessary to ensure safety and survival.

ObjectivesThere is a global movement to develop and implement community-based integrated mental health systems. The present study attempted to clarify the perceptions and attitudes of users and non-users of mental health services concerning mental illness and services in Japan.MethodsA new questionnaire was developed for this internet survey. Data from 500 outpatients with depression and 500 healthy subjects were sampled according to the demographics of the Japanese population.ResultsOver 90% of healthy subjects and over 70% of patients were unaware of the common age of onset or lifetime prevalence of mental illness. Over 90% of the healthy subjects and about 70% of the patients could not describe any services where they would feel comfortable discussing mental health problems. In both groups, “adolescents and young adults” were ranked first as a target population for mental health and illness policies. The top requirement for the integrated care systems was the promotion and awareness of correct knowledge of mental illness in both the healthy subjects and patients.ConclusionSocietal requirements could include disseminating correct knowledge, awareness-raising actions for society, and implementing services where people, especially young people, can easily consult and receive support in the community.

Abstract This study aims to investigate the contribution of visitors’ expenditure to Tokyo Metropolitan’s economy including its decomposition, the interregional repercussion effect between Tokyo and the rest of Japan, and the intersectoral propagation activities between tourism and the other sector in Tokyo based on two-region interregional input–output model and Miyazawa’s partitioned matrix multipliers. Measurement in tworegion model yielded to a higher value compared to single-region model, where domestic visitors lead the major contribution in overall, prominently on services sectors. The indirect and feedback effects to industries in Tokyo were strongly linked to tertiary sector, while spillover effect to the rest of Japan was more widely distributed. The economic activities in Tokyo were highly dependent on the industries in the rest of Japan, in similar manner as tourism on the other sectors within Tokyo. Tourism industries have strong inducible effects on the other sector. Considering these interregional and intersectoral interdependencies, improving the tourism sector in Tokyo may imply a promising effect to benefit the economy of Tokyo and subsequently other Japanese regions.

Abstract Background Combined small‐cell lung cancer (cSCLC) is a rare type of small‐cell lung cancer (SCLC) that includes both SCLC and non‐small‐cell lung cancer (NSCLC). The molecular biological mechanisms underlying the heterogeneity of histological types in combined or metachronously transformed SCLC (mtSCLC) remain unclear. This study aimed to investigate the relationship between genetic alterations and each histological component heterogeneously detected in cSCLC and mtSCLC. Methods This study included four cSCLC cases and one mtSCLC case. Formalin‐fixed and paraffin‐embedded sections of each histological component of these tumors were subjected to next‐generation sequencing (NGS) and quantitative reverse transcription‐polymerase chain reaction to investigate the genetic mutations and expression levels of neuroendocrine cell‐specific transcription factors (achaete‐scute homolog‐1 [ASCL1], brain‐2 [BRN2] also known as POU domain class 3 transcription factor 2, nuclear factor 1 B [NF1B], insulinoma‐associated protein 1 [INSM1], and thyroid transcription factor‐1 [TTF‐1]). Results NGS analysis revealed that SCLC and NSCLC components share the same somatic mutations detected most frequently in TP53, and also in RB1 and EGFR. Gene expression analysis showed ASCL1 expression was significantly lower in the NSCLC component than in the SCLC component. Conclusion We conclude that the morphological evolution of heterogeneous histological components in cSCLC may be associated with differences in ASCL1 expression levels, but not in acquired somatic gene mutations.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

This work investigated the oxidation suppression effect of a reduced graphene oxide (rGO) film applied to a Cu substrate, which may have application in electrical connectors. To ensure prolonged low electrical contact resistance, a thin GO film was formed using an electrophoretic deposition method and subsequently heated to generate rGO. The surface morphology and thickness of the rGO film were assessed using atomic force microscopy and transmission electron microscopy. The thickness of the rGO film was estimated to be 5–7 nm, and the electrical contact resistance for the Cu substrate with and without an rGO film was 20 and 8 mΩ, respectively, at a contact load of 2 N. After accelerating the oxidation of the substrate by heating for 30 min at 180 °C under a dry air atmosphere, the formation of a Cu2O layer on the Cu substrate was confirmed by Raman spectroscopy and electron energy loss spectroscopy. The thickness of this oxide layer with and without an rGO film was 1.5 and 6 nm, respectively. In addition, the electrical contact resistance for the Cu substrate with and without the rGO film was 40 and 200 mΩ, respectively, at a contact load of 2 N. These results suggest that the thin rGO coating suppressed oxidation of the metal substrate while also suppressing the increase in contact resistance.

Abstract A 44‐year‐old woman with ALK‐positive advanced adenocarcinoma of the lung was treated with crizotinib, and the lung lesions disappeared. The patient was treated with alectinib and chemotherapy, but brain metastases worsened; therefore, we performed an ALK resistance gene mutation test using plasma samples. Since no ALK resistance gene mutations were detected, we speculated that ALK inhibitors failed to achieve therapeutic effects due to poor transport to the central nervous system. Therefore, we switched to lorlatinib, and found a reduction in brain metastases. In ALK‐positive advanced lung cancer, plasma‐based resistance gene testing may be useful for treatment decisions.

Background Neuromyelitis optica spectrum disorder (NMOSD) diagnostic criteria for inflammatory demyelinating central nervous system diseases included symptomatic narcolepsy; however, no relevant case‐control studies exist. We aimed to examine the relationship among cerebrospinal fluid orexin‐A (CSF‐OX) levels, cataplexy and diencephalic syndrome; determine risk factors for low-and-intermediate CSF‐OX levels (≤200 pg/mL) and quantify hypothalamic intensity using MRI.Methods This ancillary retrospective case‐control study included 50 patients with hypersomnia and 68 controls (among 3000 patients) from Akita University, the University of Tsukuba and community hospitals (200 facilities). Outcomes were CSF‐OX level and MRI hypothalamus‐to‐caudate‐nucleus‐intensity ratio. Risk factors were age, sex, hypersomnolence and MRI hypothalamus‐to‐caudate‐nucleus‐intensity ratio >130%. Logistic regression was performed for the association between the risk factors and CSF‐OX levels ≤200 pg/mL.Results The hypersomnia group (n=50) had significantly more cases of NMOSD (p130% (AOR 6.33; 95% CI 1.18 to 34.09; p=0.032). The latter was less sensitive in predicting CSF-OX levels ≤200 pg/mL. Cases with MRI hypothalamus-to-caudate-nucleus-intensity ratio >130% had a higher rate of diencephalic syndrome (p

Abstract Purpose Multiple sleep latency test (MSLT) is performed as objective assessment of sleepiness, on the following day after polysomnography (PSG). In most clinics, patients are required to stay for 2 days. However, if patients have chronic sleep debt before the examination, even if they get adequate nocturnal sleep during the initial PSG, their sleep debt would not be fully resolved, affecting MSLT results. This may lead to improper administration of psycho‐stimulant medication. To clarify the sleep debt for the patients who showed short sleep latencies, we compared the mean sleep latencies of MSLTs. Methods Twelve hypersomnolent males, who underwent MSLTs (1st MSLT with 1 night and 2nd MSLT with more than 3 nights), were enrolled. We selected these cases based on the longer total sleep time on PSG night compared to the mean total sleep time on pre‐examination sleep logs and shortened sleep latencies on PSG. To evaluate the effect of the sleep debt for the patients who showed short sleep latencies, we extended their hospitalization or re‐hospitalized them. Results The mean sleep latency of 1st MSLT was 5.8 minutes and that of 2nd was 13.9 minutes (P

Abstract Lung cancer (LC) is the most fatal complication of idiopathic pulmonary fibrosis (IPF). However, the molecular pathogenesis of the development of LC from IPF is still unclear. Here, we report a case of IPF‐associated LC for which we investigated the genetic alterations between IPF and LC. We extracted formalin‐fixed paraffin‐embedded DNA from each part of the surgical lung tissue using a laser‐assisted microdissection technique. The mutations in each part were detected by next‐generation sequencing (NGS) using 72 lung cancer‐related mutation panels. Five mutations were found in IPF and four in LC. Almost all somatic mutations did not overlap between the IPF and LC regions. These findings suggest that IPF‐associated LC may not be a result of the accumulation of somatic mutations in the regenerated epithelium of the honeycomb lung in the IPF region.

Abstract Background Behçet’s disease (BD) is a systemic inflammatory vasculitis with both autoimmune and autoinflammatory properties. Renal involvement in BD and its spontaneous remission have been rare. We herein describe a case of parallel disease activity of BD with entero and renal involvements, followed by a spontaneous remission without corticosteroid treatment. Case presentation A 54-year-old woman who had a 4-year history of BD, maintained with colchicine treatment, suffered abdominal pain, hemorrhagic stool and diarrhea. Physical examination revealed strong tenderness in the entire abdomen. Laboratory test results showed increased levels of inflammation, and a computed tomography scan revealed edematous intestinal wall thickening with ascites. Blood and stool cultures showed no specific findings. Since she was suspected to have developed panperitonitis with acute enterocolitis, she started treatment with an antibacterial agent under bowel rest. Her abdominal symptoms gradually improved, while diarrhea and high levels of inflammatory reaction persisted. Colonoscopy revealed discontinuous abnormal mucosal vascular patterns and ulcerations in the whole colon except for the rectum, and histological analyses of the intestine demonstrated transmural mucosal infiltration of inflammatory cells without epithelioid granuloma or amyloid deposition. Based on these findings, she was diagnosed with entero BD. Meanwhile, pedal edema appeared during her hospitalization. Urinalysis results were consistent with nephrotic syndrome, thus a renal biopsy was performed. Light microscopy showed no obvious glomerular and interstitial abnormalities, whereas electron microscopy revealed foot process effacement without immune complex deposition or fibrillary structure, compatible with minimal change disease (MCD). Only with conservative therapy, her proteinuria decreased, followed by a complete remission in 3 weeks from the onset of edema. The coincident episode of MCD was finally diagnosed as renal BD that paralleled disease activity to entero BD. She started adalimumab administration, resulting in the further improvement of diarrhea and inflammatory levels. Conclusions This is the first report to demonstrate MCD as renal involvement of BD along with the disease activity of entero BD.

Pioneering the construction and application of social accounting matrix (SAM) framework in West Papua Province, Indonesia in 2018, this research aims to examine tourism-induced distribution effects on various socioeconomic groups by estimating SAM multiplier and its decomposition as well elaborating tourism influences through structural path analysis. Tourism brought significant impact on the economy with utmost overall contribution on capital factor and within decomposed cross multiplier effect. Nevertheless, impact on households decreases following a decrease in the level of household income. Accommodation and food services contributed on agricultural workers' income and employment. The latter has exceptional influence on the lowest-income rural household segment transmitted through fisheries, agricultural worker, and capital factor, that is strategic to improve livelihood and reducing regional poverty.

Although the pathogenesis of pulmonary fibrosis remains unclear, it is known to involve epithelial injury and epithelial-mesenchymal transformation (EMT) as a consequence of cigarette smoke (CS) exposure. Moreover, smoking deposits iron in the mitochondria of alveolar epithelial cells. Iron overload in mitochondria causes the Fenton reaction, leading to reactive oxygen species (ROS) production, and ROS leakage from the mitochondria induces cell injury and inflammation in the lungs. Nevertheless, the mechanisms underlying iron metabolism and pulmonary fibrosis are yet to be elucidated. In this study, we aimed to determine whether iron metabolism and mitochondrial dysfunction are involved in the pathogenesis of pulmonary fibrosis. We demonstrated that administration of the iron chelator deferoxamine (DFO) reduced CS-induced pulmonary epithelial cell death, mitochondrial ROS production, and mitochondrial DNA release. Notably, CS-induced cell death was reduced by the administration of an inhibitor targeting ferroptosis, a unique iron-dependent form of non-apoptotic cell death. Transforming growth factor-β-induced EMT of pulmonary epithelial cells was also reduced by DFO. The preservation of mitochondrial function reduced Transforming growth factor-β-induced EMT. Furthermore, transbronchial iron chelation ameliorated bleomycin-induced pulmonary fibrosis and leukocyte migration in a murine model. Our findings indicate that iron metabolism and mitochondrial dysfunction are involved in the pathogenesis of pulmonary fibrosis. Thus, they may be leveraged as new therapeutic targets for pulmonary fibrosis.

There are limited data on the clinical efficiency of afatinib in non‐small cell lung cancer (NSCLC) patients with uncommon epidermal growth factor receptor (EGFR) mutations. Moreover, the efficacy and safety of afatinib in elderly patients with these mutations has not been established. Here, we describe a case of successful treatment of a patient aged >80 years with lung adenocarcinoma positive for the uncommon EGFR L861Q mutation with low‐dose afatinib. An 83‐year‐old woman presented with cough and dyspnea. A chest computed tomography (CT) scan revealed tumors in the left upper lobe, left pleural effusion, and multiple lung metastases in both lungs. The patient was diagnosed with lung adenocarcinoma with an EGFR L861Q mutation based on cytological findings. The patient received 30 mg/day of afatinib and experienced no severe adverse events. Two weeks later, partial response was observed based on a CT scan. The results of the present case support the effectiveness and safety of low‐dose afatinib in elderly patients with EGFR L861Q mutation‐positive NSCLC.

Monolayer transition metal dichalcogenides (TMDs) have been considered as promising materials for various next-generation semiconductor devices. However, carrier doping techniques for TMDs, which are important for device fabrication, have not been completely established yet. Here, we report a monolayer p–n junction formed using in situ substitutional doping during chemical vapor deposition (CVD). We synthesized monolayer MoS2–Nb-doped MoS2 lateral homojunctions using CVD and then characterized their physical and electrical properties. The optimized growth condition enabled us to obtain spatially selective and heavy Nb doping in the edge region of a single-crystalline MoS2, thus resulting in an obvious work function difference between the inner and edge regions of the crystal. The obtained monolayer crystal demonstrated n-type and degenerate p-type semiconducting behaviors in each region, and a clear rectifying behavior across the n-type and p-type interface was observed. We believe that the results obtained can expand the research field of exploring two-dimensional homo p–n junctions, which can be important for realizing various TMD-based devices, such as diodes and field-effect transistors, with low-contact resistance.

Multilayer graphene (MLG) on a Cu substrate was successfully fabricated via a solid-source chemical vapor deposition process using fluorene as the solid source. The surface coverage of graphene was greater than 98% even at 6 min, and the MLG ratio was ∼97%, indicating that our growth method selectively promoted MLG growth from the beginning of graphene growth. The oxidation suppression characteristics of MLG were confirmed using electron back-scattered diffraction (EBSD) analysis. Cu crystal orientations were identified only under areas covered by graphene, indicating that the oxidation of Cu did not proceed at the interface between Cu and graphene. We confirmed using EBSD techniques that MLG suppresses the surface oxidation of a Cu substrate. Furthermore, we showed that EBSD was an effective tool for evaluating surface oxidation as well as surface crystal orientations.

Abstract Background Acute respiratory distress syndrome (ARDS) is a life-threatening disease; however, its treatment has not yet been fully established. The progression of ARDS is considered to be mediated by altered intercellular communication between immune and structural cells in the lung. One of several factors involved in intercellular communication is the extracellular vesicle (EV). They act as carriers of functional content such as RNA molecules, proteins, and lipids and deliver cargo from donor to recipient cells. EVs have been reported to regulate the nucleotide-binding oligomerization like receptor 3 (NLRP3) inflammasome. This has been identified as the cellular machinery responsible for activating inflammatory processes, a key component responsible for the pathogenesis of ARDS. Methods Here, we provide comprehensive genetic analysis of microRNAs (miRNAs) in EVs, demonstrating increased expression of the miRNA-466 family in the bronchoalveolar lavage fluid of a mouse ARDS model. Results Transfection of bone marrow-derived macrophages (BMDMs) with miRNA-466 g and 466 m-5p resulted in increased interleukin-1 beta (IL-1β) release after LPS and ATP treatment, which is an established in vitro model of NLRP3 inflammasome activation. Moreover, LPS-induced pro-IL-1β expression was accelerated by miRNA-466 g and 466 m-5p in BMDMs. Conclusions These findings imply that miRNA-466 family molecules are secreted via EVs into the airways in an ARDS model, and this exacerbates inflammation through the NLRP3 inflammasome. Our results suggest that the NLRP3 inflammasome pathway, regulated by extracellular vesicle miRNA, could act as a therapeutic target for ARDS.

Safety evaluation of resistance spot welds necessitates the accurate measurement of local constitutive properties. This study employed miniature mechanical tests to investigate the deformation and failure behaviors of nugget, heat affected zone (HAZ), and corona bond of resistance spot welded JSC980YL steel. A novel mini-peel test was developed to enable local fracture in HAZ for numerical inverse calibration of constitutive parameters. The fracture constants of weld zones calibrated using Cockcroft-Latham ductile failure criterion were incorporated in finite element models to predict the failure modes of spot welds in tensile-shear and cross-tension coupon tests. The result indicates that the ultimate tensile strengths of the nugget and the corona bond were 37.6% higher and 5.8% lower, respectively, than that of the base material. The nugget and HAZ exhibited ductile fracture, whereas the corona bond was brittle fracture with only 1.2% elongation. In the coupon tests, the increase of nugget diameter slowed down the damage accumulation rate in the nugget and accelerated that in the HAZ, resulting in the transition of failure mode from interfacial to pullout. The failure load of corona bond in coupon tests increased with the increase of nugget diameter while its contribution to the peak load decreased.

Background: Based on the results of the PACIFIC study, chemoradiotherapy followed by 1-year consolidation therapy with durvalumab was established as the standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC). However, some topics not foreseen in that design can be explored, including progression-free survival (PFS) and overall survival (OS) after the start of chemoradiotherapy, the proportion of patients who proceeded to consolidation therapy with durvalumab, and the optimal chemotherapeutic regimens. In Japan, the combination regimen of S-1 + cisplatin (SP), for which the results of multiple clinical studies have suggested a good balance of efficacy and tolerability, is frequently selected in clinical settings. However, the efficacy and safety of consolidation therapy with durvalumab following this SP regimen have not been evaluated. We therefore planned a multicenter, prospective, single-arm, phase II study. Methods: In treatment-naïve LA-NSCLC, two cycles of combination chemotherapy with S-1 (80–120 mg/body, Days 1–14) + cisplatin (60 mg/m 2 , Day 1) will be administered at an interval of 4 weeks, with concurrent thoracic radiotherapy (60 Gy). Responders will then receive durvalumab every 2 weeks for up to 1 year. The primary endpoint is 1-year PFS rate. Discussion: Compared with the conventional standard regimen in Japan, the SP regimen is expected to be associated with lower incidences of pneumonitis, esophagitis, and febrile neutropenia, which complicate the initiation of consolidation therapy with durvalumab, and have higher antitumor efficacy during chemoradiotherapy. Therefore, SP-based chemoradiotherapy is expected to be successfully followed by consolidation therapy with durvalumab in more patients, resulting in prolonged PFS and OS. Toxicity and efficacy results of the SP regimen in this study will also provide information important to the future establishment of the concurrent combination of chemoradiotherapy and durvalumab. Trial registration: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127

This study deals with the contribution of visitor expenditure on West Papua’s regional economy. It accomplishes three objectives: (1) to estimate the economic contribution of domestic and inbound visitor expenditure; (2) to measure the economic contribution of tourist spending at various accommodation classes; and (3) to describe the use of local commodities and labor in the regional accommodation industry. To accomplish the first and second objectives, an input-output multiplier analysis was employed. As for the third objective, interviews were conducted with 35 representatives from regional accommodation establishments. Tourism is found to contribute greatly to the regional economy, as shown from the higher overall output multiplier for tourist expenditure as compared to the regional output multiplier. The output multiplier for inbound tourist expenditure is higher than the domestic tourist. Three-star accommodations are found to be the biggest contributor with outstanding inter-sectoral impact on fisheries; food, beverage, and tobacco manufacture; and agriculture. The qualitative analysis suggests the existence of a large leakage (±90%), mainly in produce and chemicals used in daily operations. Fisheries and wood furniture are the exception. Overall, the accommodation sector absorbs a considerable extent of local labor (73%), 23% of which are Indigenous Papuans.

Abstract Background Patients with anorexia nervosa (AN) often present with pancytopenia. In most cases described in the literature, AN with pancytopenia demonstrates gelatinous marrow transformation (GMT), which is a typical bone marrow feature of malnutrition. Differentiation of AN-associated pancytopenia from other types of pancytopenia, especially idiopathic aplastic anemia (IAA), has not been studied. We encountered a case of pancytopenia in a patient with AN and relatively poor nutritional status, whose hematological findings mimicked those of IAA, specifically fatty bone marrow and absence of GMT. Case presentation The patient was a 32-year-old woman with poorly controlled AN. At 31 years of age, her body mass index (BMI) had fallen from 17.0 kg/m2 to below 13.8 kg/m2. The patient presented with ongoing fatigue and thus was examined by a hematologist. Hematological findings were consistent with IAA: peripheral blood tests revealed pancytopenia, whereas the bone marrow displayed fatty replacement without GMT. Despite the absence of bone marrow features typically seen in malnutrition, the patient’s hematological abnormalities had manifested after a decrease in body weight. Thus, although the bone marrow findings indicated IAA, we considered that the nutritional etiology of pancytopenia could not be thoroughly ruled out. Using nutritional therapy alone, the hematological abnormalities improved as BMI increased to 16.5 kg/m2. The final diagnosis was pancytopenia secondary to malnutrition because pancytopenia and fatty bone marrow improved after implementation of nutritional therapy alone. Conclusions The present case is the first documented case of AN with pancytopenia for which bone marrow examination confirmed fatty marrow without any evidence of GMT. IAA and pancytopenia secondary to malnutrition can present the same clinical findings. This case is significant because it suggests a need to differentiate between malnutrition and IAA.

Traveling for health and wellness is one of the most important tourist patterns of economic returns generated by the tourism industry, tourist destinations, and the health sector. The paper studies the potential of health tourism development in Nepal. Health tourism in Nepal especially based on natural healing resources that are mostly combined with the medical, preventive and wellness programs. They are not being used well enough, even though they are the key factor in positioning Nepal as a recognizable health tourism destination, which can generate economic growth and income. On the other hand, the trends in the world tourism predict further growth of health tourism, mostly due to the changes in people’s lifestyle. Although health tourism, a burgeoning and lucrative tourism market, has gained, increased attention in recent years, particularly in developing countries, only a few academic studies of the sector have been published. Given the scarcity of academic literature in this area, the aim of the present study is to offer a comprehensive theoretical framework for future research. Yoga, Ayurveda, meditation, and natural healing-based tourism are a new form of niche tourism, which has been rapidly growing in recent years. Keywords: Health Tourism, Wellness, Tourism Development, Potential, Nepal

Objective The standard therapies for previously treated advanced non-small cell lung cancer (NSCLC) include docetaxel (DOC). Bevacizumab (BV), an antivascular endothelial growth factor (VEGF) antibody, increases the antitumor effect of cytotoxic anticancer agents. A BV-containing combination regimen is recommended as the primary therapy for advanced non-squamous NSCLC. However, the efficacy of DOC + BV is unknown in patients with previously treated advanced NSCLC. We conducted a phase II clinical study of DOC + BV for patients with previously treated advanced non-squamous NSCLC. Methods Twenty-three patients were enrolled in this study from June 2011 through May 2014. Chemotherapy was repeated every 21 days unless there was evidence of disease progression or intolerance to the study treatment. We assessed efficacy and toxicity. Results The median progression-free survival was 30.7 weeks. The response rate was 47.8%. The most common grade ≥3 adverse events were neutropenia (20 patients, 87.0%) and febrile neutropenia (7 patients, 30.4%). Conclusions The combination of DOC and BV often resulted in serious neutropenia, suggesting that this regimen is difficult to tolerate.

The tourism industry is fragile because tourists are highly vulnerable to various crises and disasters. Because of the safety concerns of tourists, the tourism industry can suffer as a direct result of internal political conflict. Political crises can increase the perception of risk at the tourist destinations. This paper aims to examine the underlying dimension of risk perception in the context of political crises. A qualitative approach was employed to gain multiple perspectives and a deeper understanding of risk perception from an international tourist’s perspective regarding political crises. The semi-structured interview technique was selected to identify the types of risks or fears of the respondents when travelling to the political crisis destination. There were 64 respondents, comprising both potential international tourists and tourists who had previously visited Bangkok. Some respondents had experienced political crisis incidents, others had not. Thematic analysis of the data resulted in the identification of 32 political crisis risk perceptions which were grouped into 6 main themes as follows: 1. Trust in government; 2. Feeling lost; 3. Political turmoil anxiety; 4. Feeling detained; 5. Hospitality distorted; 6. Lack of political crisis knowledge/background. Understanding risk perceptions regarding political crises will help destination managers develop more effective crisis management strategies for dealing with potential political crises in their countries. Keywords: Tourists’ Risk Perceptions, Political Crises, Dimension of Political Risk Perception

Self-drive tourism (SDT) has become a potential alternative of tourism in Bali, an island that has dozens of tourist attractions scattered all over it. Unfortunately, Bali still has an insufficient integrated system of land transportation. Tourists tend to choose reasonable modes of transportation and drive themselves to reach their desired destinations by land vehicles such as passenger car or motorcycle. Consequently, roads have an important role to connect various tourist attractions and to accommodate tourists’ mobility, especially foreign tourists that have different driving attitude compared to domestic road users. Adjustments need to be made to the existing road development plan in order to maintain the expected tourists’ driving experiences. Therefore, the government needs some feasible strategies for road development as an available option of transportation in Bali Island, particularly in order to support self-drive tourism. One of the common methods to gather the information needed in making decisions related to strategies is SWOT Analysis. This study uses a qualitative approach that employs the Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis method to examine the internal and external factors comprehensively, in terms of road. Internal factors consist of the strengths and weaknesses of the road in Bali Island as tourism destination, and external factor consist of opportunities and threats presented by the road in Bali Island. The adjustment to the driving tourists will be considered in terms of four relations: strengths-opportunities (S-O), weaknesses-opportunities (W-O), strengths-threats (S-T), weakness-threats (W-T). The results of this study show that the strategy in road development is not only focused on conventional road development that relates to the physical road, access, routes and modes of transport but must be adapted to the social aspects that promote and maintain local values. The adjustment of this strategy is expected to provide an overview to the parties who play a role in developing the road to be able to encourage SDT as one of the choices for the development of sustainable tourism in Bali Keywords: Self-Drive Tourism, Road Development, Adjustment, Decision Support, SWOT Analysis

In Japan, traffic congestions often occur on the expressways connecting tourism areas with the Tokyo metropolitan area. This congestion can be mitigated if tourists delayed their departure of homeward trips to avoid peak traffic hours. A potential method to promote staggered departure times is providing the estimates of near-future traffic congestion. This study hypothesized and experimentally confirmed that some tourists would delay their departure to avoid traffic based on near-future traffic estimates. The experiment was conducted in the Yatsugatake area using a mobile application that provided this information to tourists. The results suggest that approximately 40% of self-driving tourists will perform an additional stopover if the returning route is congested and near-future traffic congestion estimate is provided.