Explore the vast range of titles available.

Sentinel lymph node biopsy (SLNB) is a widely accepted procedure for melanoma staging and treatment. The development of lymphatic mapping and SLNB, which was first introduced in 1992, has enabled surgeons to detect microscopic nodal metastases and stage-negative regional nodal basins with low morbidity. SLNB has also facilitated the selective application of regional lymph node dissection for patients with microscopic nodal metastases, enabling unnecessary lymph node dissection. In contrast, recent major randomized phase III trials (DeCOG-SLT and MSLT–II trial) compared the clinical benefit of early completion lymph node dissection with observation after detecting microscopic nodal disease. The results of those studies indicated that there was no significant difference in the survival between the two groups, although regional control was superior after early completion lymph node dissection compared to that obtained after observation. Thus, the role and value of early completion lymph node dissection worldwide are currently very limited for patients with microscopic nodal disease. However, the use of SLNB is still controversial. In addition, the recent approval of adjuvant therapy using novel agents, such as anti-programmed death-1 antibodies, and molecular targeted therapeutics may influence the skipping of complete lymph node dissection in patients with micrometastatic nodal disease in a real-world setting. Furthermore, modern neoadjuvant therapy, which is now under investigation, may have the potential to change the surgical procedure used for nodal disease. Herein, we describe the current role and value of SLNB and completion lymph node dissection and discuss the major controversies as well as the favorable future outlook.

There are about 240 butterfly species in Japan of which 15% are endangered. Grassland butterflies are the most threatened and have declined most widely, some with an extremely high rate of decline of over 80% in 40 years. The main cause is the change of “Satoyama” ecosystems, a traditional landscape including secondary woodlands, grasslands, paddy field and other habitats. However, most “Satoyama” ecosystems have been abandoned or destroyed as the landscape has been industrialized. This process has accelerated in recent years, leading to even greater impacts on butterflies. To halt this decline, the Japan Butterfly Conservation Society (JBCS) was founded in 2004 and is doing various crucial activities. Local groups have been formed and numbers have been growing steadily. Also, public awareness toward conservation of the natural environment has been increasing and conservation groups related to “Satoyama” exceed 1000. Government policy on biodiversity has developed since The National Biodiversity Strategy of Japan was published in 1995. JBCS has set targets to prevent threatened butterflies from becoming extinct at national and regional level. However, many difficulties remain and a greater effort is needed to develop a social system to maintain “Satoyama” as an industry. Although interest in the conservation of Japanese butterflies began several decades ago, full scale conservation activities have only started recently and future progress is expected.

The glucocorticoids (GCs)-glucocorticoid receptor (GR)-SGK1-NDRG1 pathway plays an important role in the response of tumor cells to various stresses including chemotherapy. In many solid tumors, the GCs-GR pathway acts as a tumor suppressor; however, its function varies depending on the type of cancer. This study investigated the relationship between the GR-SGK1-NDRG1 pathway and lung adenocarcinoma recurrence and overall survival. Lung adenocarcinoma cases (n=121, Stage I-III) were included. Immunohistochemistry for GR, N-myc downstream regulated gene 1 (NDRG-1), serum and glucocorticoid-induced protein kinase 1 (SGK-1), Ki-67, and programmed cell death ligand 1 (PD-L1) was performed to examine their relationship with clinicopathological features, recurrence, and prognosis. SGK-1 and NDRG-1 were significant prognostic factors. Recurren ce was more likely in the SGK-1, NDRG-1, and Ki-67 high/positive groups. The GR-SGK1-NDRG1 pathway may be involved in the recurrence and prognosis of lung adenocarcinoma.

The capability of the Automatic Identification System (AIS) to provide real-time worldwide coverage of ship tracks has made it possible for maritime authorities to utilize AIS as a means of surveillance to identify anomalies. Anomaly detection in maritime traffic is crucial as anomalous behavior may be a sign of either emergencies or illegal activities. Anomalous ships are recognized based on their behavior by manual examination. Such work requires extensive effort, especially for nationwide surveillance. To deal with this, researchers proposed computational methods to analyze vessel behavior. However, most approaches are region-dependent and require a profile of normality to detect anomalies, and amongst the six types of anomaly, loitering is the least explored. Loitering is not necessarily anomalous behavior as it is common for certain types of ships, such as pilot boats and research vessels. However, tankers and cargo ships normally do not engage in loitering. Based on 12-month manually examined data, nearly 60% of the identified anomalies were loitering, particularly for those of types cargo and tanker. Although manual identification is inefficient, automatically identifying abnormal vessels by merely implementing computing algorithms is not yet feasible. It still needs subject matter experts’ assessments. This study proposes a region-independent method to automatically detect loitering without training normal instances and produces a ranked list of loitering vessels to facilitate further anomaly investigation. First, the loitering spatiotemporal characteristics are defined: (1) movement of frequent course change, with a certain speed, within a certain spatial range, (2) movement of frequent course change within traversed geodetic distance, (3) might demonstrate frequent extreme turning, and (4) extreme turning produces a significant discrepancy between the course over ground and the heading of the ship. Then, the characteristics are quantified by manipulating the dynamic information of AIS messages. Finally, the parameters to determine a loitering trajectory are formulated by comparing the rate of course change, speed, and the discrepancy between heading and course with the area of spatial range enclosing the trajectory and the geodetic distance between the start and end point. The loitering score of each trajectory is calculated with the parameters, and the Isolation Forest algorithm is employed to establish a threshold and rank. Then, geographic visualization is created for intuitive evaluation. An experiment was conducted on a real-world dataset covering a sea area of 610,116.37 km2. The results prove the efficacy of the proposed method. It remarkably outperforms the existing approach with 97% accuracy and 92% F-score. The experiment produces a ranked list of loitering vessels and an intuitive visualization in the relevant geographic area. In the realworld scenario, they are practical means to support further examination by human operators.

Background Passengers on the cruise ship Diamond Princess (DP), which departed Yokohama on 20 January 2020, were found to be infected with the new coronavirus after arrival in Hong Kong. Passengers and crew were not allowed to disembark, instead being quarantined on board; an onboard pandemic resulted. Many passengers were elderly and in need of medications; pharmacists and other professionals, including the author, were assigned to provide medical support (the author participated on two occasions). Many passengers were not Japanese nationals; those who required medicines not sold in Japan received analogs of medicines that are sold in Japan. Pharmacists were required to complete medication guidance documents (in English). The author considered that by using this experience as teaching material, pharmacy students would not only learn English but also become educated in terms of drug therapy. Method The author created an exercise for second-year students at Teikyo University in which they were required to provide real-world medical support. The educational effects were measured by analyzing the answers to questionnaires completed before and after the exercise and ‘Impressions of the exercise’ homework. Results Using real emergency events as a teaching tool enhanced students’ motivation to learn English and pursue professional pharmacy education (the latter was scheduled to begin in earnest in the third year). At that time, the new coronavirus was poorly understood. The author’s experiences taught students that medical workers are educated to offer care even when they are at risk of infection. Translation software (a form of artificial intelligence [AI]) was used to create medication guidance documents in English. The students learnt that if AI translations, i.e., medication guidance documents in English, were accepted at face value, they would be held responsible if the documents were in error. Conclusion By both listening to the author’s lecture on a real-world medical support situation and completing an assignment, students learned many things that are difficult to teach via lectures alone, including the dangers arising when using AI technology in clinical settings and the mindset of medical professionals.

Context:Approximately half of patients with primary aldosteronism (PA) have clinically evident disease according to clinical (hypertension) and/or laboratory (aldosterone and renin levels) findings but do not have nodules detectable in routine cross-sectional imaging. However, the detailed histopathologic, steroidogenic, and pathobiological features of cross-sectional image–negative PA are controversial.Objective:To examine histopathology, steroidogenic enzyme expression, and aldosterone-driver gene somatic mutation status in cross-sectional image–negative hyperaldosteronism.Methods:Twenty-five cross-sectional image–negative cases were retrospectively reviewed. In situ adrenal aldosterone production capacity was determined using immunohistochemistry (IHC) of steroidogenic enzymes. Aldosterone-driver gene somatic mutation status (ATP1A1, ATP2B3, CACNA1D, and KCNJ5) was determined in the CYP11B2 immunopositive areas [n = 35; micronodule, n = 32; zona glomerulosa (ZG), n = 3] using next-generation sequencing after macrodissection.Results:Cases were classified as multiple adrenocortical micronodules (MN; n = 13) or diffuse hyperplasia (DH) of ZG (n = 12) based upon histopathological evaluation and CYP11B2 IHC. Aldosterone-driver gene somatic mutations were detected in 21 of 26 (81%) of CYP11B2-positive cortical micronodules in MN; 17 (65%) mutations were in CACNA1D, 2 (8%) in KCNJ5, and 1 each (4% each) in ATP1A1 and ATP2B. One of 6 (17%) of nodules in DH harbored somatic aldosterone-driver gene mutations (CACNA1D); however, no mutations were detected in CYP11B2-positive nonnodular DH areas.Conclusion:Morphologic evaluation and CYP11B2 IHC enabled the classification of cross-sectional image–negative hyperaldosteronism into MN and DH. Somatic mutations driving aldosterone overproduction are common in micronodules of MN, suggesting a histological entity possibly related to aldosterone-producing cell cluster development.We reviewed CYP11B2 immunolocalization and aldosterone-driver gene somatic mutation status of cross-sectional image–negative hyperaldosteronism and developed histological classification.

Cancer stem cells (CSCs) are responsible for therapy resistance and share several properties with normal stem cells. Here, we show that brain‐expressed X‐linked gene 2 (BEX2), which is essential for dormant CSCs in cholangiocarcinoma, is highly expressed in human hepatocellular carcinoma (HCC) lesions compared with the adjacent normal lesions and that in 41 HCC cases the BEX2high expression group is correlated with a poor prognosis. BEX2 localizes to Ki67‐negative (nonproliferative) cancer cells in HCC tissues and is highly expressed in the dormant fraction of HCC cell lines. Knockdown of BEX2 attenuates CSC phenotypes, including sphere formation ability and aldefluor activity, and BEX2 overexpression enhances these phenotypes. Moreover, BEX2 knockdown increases cisplatin sensitivity, and BEX2 expression is induced by cisplatin treatment. Taken together, these data suggest that BEX2 induces dormant CSC properties and affects the prognosis of patients with HCC. BEX2 is essential for dormant cancer stem cell and affects patients’ prognosis in hepatocellular carcinoma. BEX2 could be a promising therapeutic target.

Mycobacterium leprae ( M . leprae ) is the etiological agent of leprosy, and the skin lesions of lepromatous leprosy are filled with numerous foamy or xanthomatous histiocytes that are parasitized by M . leprae . Lipids are an important nutrient for the intracellular survival of M . leprae . In this study, we attempted to determine the intracellular lipid composition and underlying mechanisms for changes in host cell lipid metabolism induced by M . leprae infection. Using high-performance thin-layer chromatography (HPTLC), we demonstrated specific induction of triacylglycerol (TAG) production in human macrophage THP-1 cells following M . leprae infection. We then used [ 14 C] stearic acid tracing to show incorporation of this newly synthesized host cell TAG into M . leprae . In parallel with TAG accumulation, expression of host glycerol-3-phosphate acyltransferase 3 (GPAT3), a key enzyme in de novo TAG synthesis, was significantly increased in M . leprae -infected cells. CRISPR/Cas9 genome editing of GPAT3 in THP-1 cells ( GPAT3 KO) dramatically reduced accumulation of TAG following M . leprae infection, intracellular mycobacterial load, and bacteria viability. These results together suggest that M . leprae induces host GPAT3 expression to facilitate TAG accumulation within macrophages to maintain a suitable environment that is crucial for intracellular survival of these bacilli.

Background Liquid biopsy, which facilitates minimally invasive analysis of body fluid samples, has considerable potential as a diagnostic and prognostic tool in various cancers. Analysis of circulating tumour cells, circulating tumour DNA, and exosomes in liquid biopsies has advantages and disadvantages. However, their utility in rare cancers, such as malignant bone and soft tissue tumours, remains unknown. In this study, we examined the levels of circulating cell-free tumour RNA (cfRNA) in the blood of patients with malignant bone and soft tissue tumours harbouring specific fusion genes, to explore the relationship between fusion gene expression in the blood and therapeutic response and disease status, and to validate the clinical utility of liquid biopsy. Methods The study involved 3 cases (7 samples) of Ewing’s sarcoma, 6 cases (12 samples) of myxoid liposarcoma, and 1 case (2 samples) of synovial sarcoma with specific fusion genes. Fusion gene analysis was performed using tumour tissue samples to identify breakpoints. Primers for liquid biopsy were designed based on the fusion genes identified. cfRNA was extracted from each patient’s plasma and used for reverse transcription polymerase chain reaction (RT-PCR) with the designed primers. The RT-PCR product was subjected to Sanger sequencing. Results Fusion gene breakpoints were identified in 10 samples from 6 cases. The fusion gene detection rate in the blood was 100% at both naïve status and symptom exacerbation in patients with Stage IV disease. In patients with Stage III disease progressing to Stage IV, the fusion gene was detected in the blood prior to imaging tests. Conclusions The detection of specific fusion genes from cfRNAs shows potential for monitoring the progression of fusion-related sarcomas in the context of chemotherapy.

Background It is important to confirm CD30 expression in T-cell lymphoma cases, but immunohistochemical staining for CD30 is not commonly performed and no comparison has been done between the results of flow cytometry (FCM) and immunohistochemical staining for CD30. Therefore, we devised a notation that we termed proportion of immunoreactivity/expression for FCM (PRIME-F notation), based on the cellular proportion showing different antigen-antibody reactivity. Methods We retrospectively compiled 211 cases of T-cell lymphoma, assessed via FCM, from major hospitals in Miyagi Prefecture from January 2012 to January 2019, and compared 52 of these cases with the immunohistochemical immunoreactive (IR) pattern of CD30 (PRIME-I notation). The PRIME-F notation was divided into five levels: notations starting with “-” followed by 3, 2, and 1 “>” correspond to level-I, level-II, or level-III; notations starting with “(dim)+” correspond to level-IV; and those starting with “+” or “(bright)+” correspond to level-V. Results The 52 cases of PRIME-F notation with “+” included 16 cases of peripheral T-cell lymphoma (PTCL/NOS), 3 of follicular T-cell lymphoma (FTL), 3 of angioimmunoblastic T-cell lymphoma (AITL), 6 of extranodal NK/T-cell lymphoma/nasal type (ENKL), 18 of adult T-cell lymphoma (ATL), and 6 cases of anaplastic large cell lymphoma (ALCL). Eight of the 52 cases were immunohistochemically CD30-negative. In the PRIME-F level-I to III group (excluding false-positive cases), 21.7% (5 out of 23 cases) were < 10% positive for CD30 upon immunohistochemistry (IHC). Contrarily, in the level-IV & -V group, no CD30 positivity rate of < 10% upon IHC was found (0%) ( p  = 0.0497). In level-IV, 42.9% of cases presented a CD30 negative rate  >  1/3 upon IHC, while in level-V, only 7.1% (one out of 14 cases) did. The CD30 negative rate tended to be low ( p  = 0.0877) in level-V. Conclusions To our knowledge, this is the first report describing the correspondence between FCM and immunohistochemistry findings for CD30 through newly proposed notations. The PRIME-F and PRIME-I notations for CD30 showed a minor positive correlation. The PRIME notation is considered universally applicable to antibodies, and notations of both FCM and IHC show great potential for big data.