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Geotagged social media data have been used widely for visitor monitoring in protected areas. The data might, however, over or underestimate visitors from specific countries due to nationality bias, i.e., differences between nationality of actual visitors versus those visitors who post on social media. This study aimed to quantify nationality bias in social media data for visitor monitoring. We conducted a questionnaire survey in Nikko National Park, Japan. Questions covered the nationality of visitors and their usage of social media, and other visitor attributes and behavior. Foreign visitors had significantly different attributes and behaviors compared to Japanese. Non-Japanese Asian visitors were overrepresented in Instagram and Facebook data. In comparison, the X platform was more representative of all visitors. Nationality bias in different platforms needs more attention and further study in different areas.

In the pursuit of sustainable national park management, park managers need to understand the interests and activities of their diverse visitors in order to conserve the natural environment and offer a better visitor experience. This study aimed to examine the effectiveness of using non-geotagged social media data from posts by park visitors for park management in comparison with geotagged data, which has been studied more extensively. We compared (1) visitors' sociodemographic characteristics between geotagged and non-geotagged social media users through an onsite survey in Nikko National Park, Japan, and (2) the content of geotagged and non-geotagged photos shared within the study area on X (formerly Twitter). Our results showed that visitors in their 30s and 40s and foreign visitors had a greater tendency to use geotags. Non-geotagged photos more frequently and deeply capture nature-based activities and interests, including activities on trails, such as mountain climbing and hiking, and an interest in diverse animals and plants and landscapes that are less accessible. These findings indicate that non-geotagged social media data may have less age and nationality bias and advantages over the more widely-used geotagged data in capturing various nature-based experiences offered by national parks. Leveraging both geotagged and non-geotagged data can enable park managers to implement sustainable practices catering to a broader range of visitor interests and activities, contributing to the overarching goal of sustaining the natural environment while also enriching the visitor experience within national parks. [ABSTRACT FROM AUTHOR]

Background: Carpal tunnel syndrome is occasionally associated with basal joint arthritis and is more common in postmenopausal women than in the general population. Currently, more evidence is needed to describe changes in the carpal tunnel after basal joint arthroplasty (BJA) of the thumb and to determine whether it is better to combine the release of the flexor retinaculum. The purpose of this study was to clarify the changes in the carpal tunnel cross-sectional area and carpal tunnel shape after complete removal of the trapezium during BJA of the thumb, according to computed tomography (CT) findings. Methods: We retrospectively investigated the carpal tunnel cross-sectional area with CT findings obtained pre- and postoperatively in 20 postmenopausal women who underwent BJA of the thumb. Results: The average horizontal plane area of the carpal tunnel was 1.11 ± 0.19 cm2 preoperatively and increased to 1.23 ± 0.2 cm2 at 3 months postoperatively (p = 0.0411). The ratio of the longitudinal diameter to the horizontal diameter was significantly increased from 0.6 ± 0.13 preoperatively to 1.23 ± 0.2 postoperatively (p = 0.0439). Conclusions: The increase in the carpal tunnel cross-sectional area was confirmed after BJA of the thumb. This increased carpal tunnel cross-sectional area changed as the longitudinal diameter increased, without changes in the horizontal diameter. Level of Evidence: Level IV (Therapeutic) [ABSTRACT FROM AUTHOR]

Reaction of Me3Al with the 3',4'-epoxides derived from 9-(3-deoxy-beta-D-glycero-pent-3-enofuranosyl)adenine is investigated in detailed. Results reveal that the stereoselectivity of epoxide ring opening varied significantly upon changing the amount of Me2Al, the solvent, the O-silyl protecting group, and the reaction temperature.

Epoxidation of 3',5'-O-(di-tert-butylsilylene)-1',2'-unsaturated uridine with dimethyldioxirane proceeded from the alpha-face to give the 1', 2'-alpha-epoxide. Findings show that protection of the N(super3)-position of 3',5'-O-(di-tert-butylsilylene)-1',2'-unsaturated uridine either with a benzyloxymethyl or benzoyl group led to the exclusive formation of the desired beta-anomers.

Background: Treatment with epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) leads to initial response in most patients with EGFR‐mutated non‐small cell lung cancer (NSCLC). In contrast, little is known of the subpopulation of patients with NSCLC with EGFR mutations who exhibit clinical outcomes that require treatment with immune checkpoint inhibitors (ICIs). Therefore, to identify eligible cases to treat with ICIs, we retrospectively analyzed the correlation between clinical features and the efficacy of ICIs in patients with EGFR mutations. Patients and Methods: We retrospectively analyzed patients with advanced NSCLC harboring EGFR mutations who were treated with ICIs after developing resistance to EGFR‐TKIs between February 2016 and April 2018 at 6 institutions in Japan. The association between clinical outcomes and the efficacy of ICIs was investigated. Results: We enrolled 27 patients who harbored EGFR‐activating mutations. The objective response and disease control rates were higher in patients with uncommon EGFR mutations than in those with common EGFR mutations (71% vs 35.7% and 57% vs 7%, P = 0.14 and P < 0.01, respectively). Patients with uncommon EGFR mutations or without T790M mutations exhibited a significantly longer median progression‐free survival than those with common EGFR mutations or with T790M mutations (P = 0.003 and P = 0.03, respectively). Conclusion: Patients with uncommon EGFR mutations and without T790M mutations are associated with the best outcomes for treatment with immunotherapy among those with EGFR‐mutated NSCLC, based on retrospective analysis. Further research is needed to validate the clinical biomarkers involved in ICI responders with EGFR mutations. [ABSTRACT FROM AUTHOR]

Background: Confirmatory diagnosis of visceral leishmaniasis (VL), as well as diagnosis of relapses and test of cure, usually requires examination by microscopy of samples collected by invasive means, such as splenic, bone marrow or lymph node aspirates. This causes discomfort to patients, with risks of bleeding and iatrogenic infections, and requires technical expertise. Molecular tests have great potential for diagnosis of VL using peripheral blood, but require well-equipped facilities and trained personnel. More user-friendly, and field-amenable options are therefore needed. One method that could meet these requirements is loop-mediated isothermal amplification (LAMP) using the Loopamp Leishmania Detection Kit, which comes as dried down reagents that can be stored at room temperature, and allows simple visualization of results. Methodology/Principal findings: The Loopamp Leishmania Detection Kit (Eiken Chemical Co., Japan), was evaluated in the diagnosis of VL in Sudan. A total of 198 VL suspects were tested by microscopy of lymph node aspirates (the reference test), direct agglutination test-DAT (in house production) and rK28 antigen-based rapid diagnostic test (OnSite Leishmania rK39-Plus, CTK Biotech, USA). LAMP was performed on peripheral blood (whole blood and buffy coat) previously processed by: i) a direct boil and spin method, and ii) the QIAamp DNA Mini Kit (QIAgen). Ninety seven of the VL suspects were confirmed as cases by microscopy of lymph node aspirates. The sensitivity and specificity for each of the tests were: rK28 RDT 98.81% and 100%; DAT 88.10% and 78.22%; LAMP-boil and spin 97.65% and 99.01%; LAMP-QIAgen 100% and 99.01%. Conclusions/Significance: Due to its simplicity and high sensitivity, rK28 RDT can be used first in the diagnostic algorithm for primary VL diagnosis, the excellent performance of LAMP using peripheral blood indicates that it can be also included in the algorithm for diagnosis of VL as a simple test when parasitological confirmatory diagnosis is required in settings that are lower than the reference laboratory, avoiding the need for invasive lymph node aspiration. [ABSTRACT FROM AUTHOR]

This study aimed to assess analytical parameters of a prototype LAMP kit that was designed for detection of Trypanosoma cruzi DNA in human blood. The prototype is based on the amplification of the highly repetitive satellite sequence of T.cruzi in microtubes containing dried reagents on the inside of the caps. The reaction is carried out at 65°C during 40 minutes. Calcein allows direct detection of amplified products with the naked eye. Inclusivity and selectivity were tested in purified DNA from Trypanosoma cruzi stocks belonging to the six discrete typing units (DTUs), in DNA from other protozoan parasites and in human DNA. Analytical sensitivity was estimated in serial dilutions of DNA samples from Sylvio X10 (Tc I) and CL Brener (Tc VI) stocks, as well as from EDTA-treated or heparinized blood samples spiked with known amounts of cultured epimastigotes (CL Brener). LAMP sensitivity was compared after DNA extraction using commercial fiberglass columns or after “Boil & Spin” rapid preparation. Moreover, the same DNA and EDTA-blood spiked samples were subjected to standardized qPCR based on the satellite DNA sequence for comparative purposes. A panel of peripheral blood specimens belonging to Chagas disease patients, including acute, congenital, chronic and reactivated cases (N = 23), and as well as seronegative controls (N = 10) were evaluated by LAMP in comparison to qPCR. LAMP was able to amplify DNAs from T. cruzi stocks representative of the six DTUs, whereas it did not amplify DNAs from Leishmania sp, T. brucei sp, T. rangeli KPN+ and KPN-, P. falciparum and non-infected human DNA. Analytical sensitivity was 1x10-2 fg/μL of both CL Brener and Sylvio X10 DNAs, whereas qPCR detected up to 1x 10−1 fg/μL of CL Brener DNA and 1 fg/μl of Sylvio X10 DNA. LAMP detected 1x10-2 parasite equivalents/mL in spiked EDTA blood and 1x10-1 par.eq/mL in spiked heparinized blood using fiberglass columns for DNA extraction, whereas qPCR detected 1x10-2 par.eq./mL in EDTA blood. Boil & Spin extraction allowed detection of 1x10-2 par.eq /mL in spiked EDTA blood and 1 par.eq/ml in heparinized blood. LAMP was able to detect T.cruzi infection in peripheral blood samples collected from well-characterised seropositive patients, including acute, congenital, chronic and reactivated Chagas disease. To our knowledge, this is the first report of a prototype LAMP kit with appropriate analytical sensitivity for diagnosis of Chagas disease patients, and potentially useful for monitoring treatment response. [ABSTRACT FROM AUTHOR]

Upon reaction of the 3',4'-unsaturated adenosine derivative 2 with N-iodosuccinimide (NIS) and thiophenol, an unexpected electrophilic hydrophenyisulfanylation proceeded to provide 4'-phenyisulfanylcordycepin 7 in 79% yield with the ratio 7a/7b = 6.6/1. A study of the reaction mechanism revealed that hydrogen iodide (HI) generated from NIS and PhSH acted as an active species. On the basis of a deuterium experiment using PhSD, initial protonation occurred at the β face of the double bond to furnish the β-π complex III, which underwent and addition of PhSH as a major pathway. Nucleophilic substitution of N6-pivaloylated 9 with various alcohols in the presence of W-bromosuccinimide (NBS)gave the respective 4'-α-alkoxycordycepins 15a-21a as the major stereoisomers. Use of DAST in place of an alcohol gave the 4 -α-fluoro analogue 23a stereoselectively. Radical-mediated carbon--carbon bond construction was also applicable to 7, giving 4'-α-allylcordycepin (24a) and 4'-α-cyanoethylcordycepin (25) derivatives. [ABSTRACT FROM AUTHOR]

The title compound (13) has been synthesized from 5'-O-TBS-thymidine (8) through a highly stereoselective iodination of the 3'-hydroxyl group utilizing I2/PPh3/imidazole. This method provides an efficient entry to the 3',4'-unsaturated derivative (7). [ABSTRACT FROM AUTHOR]

Nucleophilic substitution between the 4′-benzoyloxy derivative of cordycepin (3′-deoxyadenosine) and A1Me3 proceeds mostly with retention of configuration at the 4′-position: the 4′-benzoyloxy substrate having the β-D-configuration (8a) gave the 4′-methylated β-D-nucleoside (9a) with a high diastereomeric excess, while the substrate 8b having the opposite 4′-configuration gave the corresponding α-L-isomer (9b) with a comparatively lower stereoselectivity. The SNi mechanism is proposed for this reaction (from 8 to 9). The polarity of the solvent has a significant influence on the stereoselectivity, especially for the formation of 9b. [ABSTRACT FROM AUTHOR]

Preparation of 1',2 '-, 3 ',4 '-, and 4 ',5 '-epoxy derivatives of nucleosides and their use for the stereoselective synthesis of 1'- and 4 '-branched analogues are described. [ABSTRACT FROM AUTHOR]

Upon epoxidation with dimethyldioxirane, the 2′,5′-bis-O-silyl derivatives of 9-(3-deoxy-β-D-glycero-pent-3-enofuranosyl)adenine gave the respective ‘3′,4′-up’ epoxides exclusively. Reaction between these epoxides and Me3Al was investigated in detail. It was found that the stereoselectivity of epoxide ring opening (anti versus syn) varied significantly upon changing the amount of Me3Al, the solvent, the O-silyl protecting group, and the reaction temperature. A possible reaction mechanism is proposed. [ABSTRACT FROM AUTHOR]

Candidemia, a complication often affecting immunocompromised patients, is a common cause of acute lung injury. Yeast-phase Candida albicans has been shown to express a protein that is antigenically and structurally related to Mac-1. C. albicans is reported to stimulate intercellular adhesion molecule 1 (ICAM-1)expression on endothelial cells. In this study, the authors examined the role of ICAM-1 in acute lung injury induced by candidemia. The authors cultured rat pulmonary artery endothelial cells (RPAEC)and investigated the effect of anti-ICAM-1antibodies on adhesion of C. albicans to RPAEC. In addition, the authors administered anti-ICAM-1 antibodies to rats to examine the effect of the antibodies on experimentally induced candidemia. Survival rates, lung wet-to-dry (W/D) weight ratios, bronchoalveolar lavage (BAL) fluid, histopathological findings, and colony-forming units (CFUs)of lung C. albicans were examined. The adherence of C. albicans to RPAEC was significantly decreased by anti-ICAM-1 antibodies. Anti-ICAM-1 antibodies significantly increased survival, decreased lung W/D weight ratios, decreased neutrophil counts in the BAL fluid, reduced microscopic lung injury, and decreased the quantity of lung C. albicans. These results indicate that ICAM-1plays a role in adherence of C. albicans to pulmonary vascular endothelial cells, which likely leads to invasion of lung tissue by the organism. [ABSTRACT FROM AUTHOR]

AbstractBackground: Few articles describe stage and pathology distribution of prostate cancer by age, yet understanding these topics may provide clues to the etiology of this disease. The present study describes the distribution of stage and pathology of prostate cancer in terms of age and considers effective detection of early stage cancer by mass screening (MS). Methods: Data presented in this study were based on patient’s files from MS and the Gunma Urological Oncology Study Group (GUOSG) registry from 1981 to 1996 in Gunma Prefecture, Japan. Results: Age did not significantly correlate with stage distribution among the GUOSG patients, whereas stage tended to advance with age among the MS patients. Stage B was detected more frequently than any other stage in all age groups of the MS patients, whereas stage C and stage D were detected at similar rates in all age groups. After prostate specific antigen (PSA) had been introduced in MS, the percentage of early stage cancer increased at an earlier age. Pathology distribution did not significantly differ in any group. Conclusions: The data obtained from MS cancer patients showed that tumor stage tends to advance with age. We believe that the younger age group should be examined by MS using PSA to effectively detect early prostate cancer. [ABSTRACT FROM AUTHOR]

Presents information on a study which investigated the effect of the simultaneous partial substitution of lanthanum and cobalt for the magnetic properties of anisotropic strontium (Sr) ferrite magnets. Ways on how to increase the residual flux density and coercive force of anisotropic Sr ferrite magnets; Methodology; Results and conclusion.

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Osimertinib is a mutant-selective EGFR inhibitor that is effective against non-small cell lung cancer (NSCLC) in patients with the EGFR-T790M mutation, who are resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, the factors affecting response to osimertinib treatment are unknown. In this retrospective study, 27 NSCLC patients with the EGFR-T790M mutation were enrolled at five institutions in Japan. Among several parameters tested, the progression-free survival (PFS) associated with the initial EGFR-TKIs was positively correlated with the PFS after osimertinib treatment (p = 0.021). The median PFS following osimertinib treatment and the overall survival (OS) were longer in patients who responded to osimertinib than in those who did not (17.7 months versus 3.5 months, p = 0.009 and 24.2 months versus 13.5 months, p = 0.021, respectively). A multivariate analysis demonstrated that the PFS with initial EGFR-TKIs was significantly related to the PFS with osimertinib treatment (p = 0.035), whereas osimertinib response was significantly related to the PFS and OS with osimertinib treatment (p = 0.016 and p = 0.006, respectively). Our retrospective observations indicate that PFS following the initial EGFR-TKI treatment and the response rate to osimertinib might be promising predictors for effective osimertinib treatment in NSCLC patients with the EGFR-T790M mutation. [ABSTRACT FROM AUTHOR]

Background: Current clinical trials demonstrated that combination regimens comprising chemotherapy and immunotherapy lead to better patient outcomes compared to chemotherapy alone as the first line of treatment for non-small cell lung cancer (NSCLC). In addition, the combination therapy of docetaxel (Doc) and ramucirumab (Ram) was considered one of the standard treatments for advanced or relapsed NSCLC patients. However, little is known about the therapeutic responders of this combination therapy among previously treated NSCLC patients. In the present study, we aimed to identify predictive factors for therapeutic response, including programmed death-ligand 1 (PD-L1) expression in tumors, for Doc treatment in combination with Ram., Methods: We retrospectively analyzed a total of 135 advanced or relapsed NSCLC patients who were refractory to platinum-based chemotherapy at eleven institutions in Japan between July 2016 and November 2018., Results: Our observations showed that PD-L1 expression in tumors is not associated with the efficacy of combined therapy of Doc and Ram in previously treated NSCLC patients. Analysis of the patient clinical profiles indicated that prior treatment with immune checkpoint inhibitors (ICIs) is a reliable predictor for the good progression-free survival (PFS) to this combination therapy (P=0.041)., Conclusions: Our retrospective study indicated that combination regimens comprising chemotherapy and ICIs followed by Doc and Ram could be an optimal therapeutic option for NSCLC patients regardless of the PD-L1 status of tumors. Further investigations are required to strengthen clinical evidence demonstrating the effectiveness of the combination therapy of Doc plus Ram in previously treated NSCLC patients., Competing Interests: Conflicts of Interest: Dr. Yamada reports receiving research grants from Pfizer Inc., Boehringer Ingelheim Japan Inc., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., and Chugai Pharmaceutical Co., Ltd. Dr. Uchino reports receiving research grants from Eli Lilly Japan K.K., AstraZeneca K.K., and Boehringer Ingelheim Japan Inc. Dr. Takayama reports receiving research grants from Chugai-Roche Co., and Ono Pharmaceutical Co., and personal fees from AstraZeneca Co., Chugai-Roche Co., MSD-Merck Co., Eli Lilly Co., Boehringer-Ingelheim Co., and Daiichi-Sankyo Co. The other authors have no conflicts of interest to declare.

Branched sugar nucleosides have attracted much attention due to their biological activities. We have demonstrated that epoxysugar nucleosides serve as versatile precursor for the stereo-defined synthesis of these nucleoside derivatives on the basis of its ring opening with organoaluminum or organosilicon reagents. In this review article, novel methods for the synthesis of nucleoside analogues branched at the 1' and 4'-position will be described. During this study, we could discover an anti-HIV agent, 4'-ethynylstavudine (Festinavir). Festinavir showed more potent anti-HIV activity than the parent compound stavudine (d4T). Other significant properties of Festinavir are as follows: 1) much less toxic to various cells and also to mitochondorial DNA synthesis than d4T, 2) better substrate for human thymidine kinase than d4T, 3) resistant not only to chemical glycosidic bond cleavage but also to catabolism by thymidine phosphorylase, 4) the activity improves in the presence of a major mutation, K103N, associated with resistance to non-nucleoside reverse transcriptase inhibitors. Detailed profile of the antiviral activities, biology and pharmacology of Festinavir are also described.