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Wei-Chung Tsai,1 Fang-Ling Liu,1 Ming-Hsi Huang,2 Chung-Hsiung Huang1,3 1Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan; 2National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan; 3Center for Marine Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, TaiwanCorrespondence: Chung-Hsiung Huang, Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan, Tel +886-2-2462-2192 ext 5116, Email huangch@mail.ntou.edu.twBackground: Intravaginal vaccination is an encouraging approach to prevent infectious vaginitis, with nanoemulsions showing effectiveness as mucosal adjuvants.Purpose: This study aimed to formulate a nanoemulsion incorporating Porphyra oligosaccharide (PO@NE) and assess its effectiveness as a mucosal adjuvant in intravaginal vaccines against candidal vaginitis.Materials and Methods: PO@NE was prepared, and the stability, immunomodulatory activity and cytotoxicity were screened in vitro. Further, the preventive effect of PO@NE as adjuvants for heat-killed Candida albicans (HK-CA) vaccines was explored in a murine model of candidal vaginitis, in comparison with those supplemented with polysaccharide (PP@NE). The mice were intravaginally vaccinated with 106 HK-CA cells, suspended in 1% NE without or with either PO or PP at a final concentration of 6.5 μg/mL, in a total volume of 20 μL. This vaccination was intravaginally administered once a week for 3 weeks. One week following the final vaccination, the mice underwent an intravaginal challenge with 107 C. albicans cells. One week after the challenge, the mice were euthanized to isolate serum, spleen, vaginal washes, and vaginal tissues for analysis.Results: PP@NE and PO@NE, with diameters approximately around 100 nm, exhibited exceptional stability at 4°C and low cytotoxicity when used at a concentration of 1% (v/v). Intravaginal vaccination with HK-CA adjuvanted with PO@NE effectively protected against candidal vaginitis evidenced by less Candida hyphae colonization, milder mucosal damage and cell infiltration. Moreover, enhanced mucosal antibody production, induction of T helper (Th)1 and Th17-related immune responses, enlarged the population of CD8+ cells, and elevated vaginal microflora diversity were observed in vaccinated mice. Interestingly, the potency was rather attenuated when PO@NE was replaced with PP@NE.Conclusion: These findings indicate PO@NE as a HK-CA vaccine adjuvant for candidal vaginitis prevention via enhancement of both cellular and humoral immunity and modulation of vaginal microflora, emphasizing further intravaginal vaccination development.Keywords: Candida albicans, mucosal vaccine adjuvant, nanoemulsion, Porphyra oligosaccharide, vaginitis

Mei-Hsuen Huang,1 Yu-Fan Liu,2,3 Oswald Ndi Nfor,4 Shu-Yi Hsu,4 Wei-Yong Lin,5– 7 Yuan-Shiun Chang,1 Yung-Po Liaw4,8 1Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan; 2Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan; 3Division of Allergy, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; 4Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, 40201, Taiwan; 5Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan; 6Department of Medical Research, China Medical University Hospital, Taichung, 40447, Taiwan; 7Brain Diseases Research Center, China Medical University, Taichung, 40402, Taiwan; 8Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung City, 40201, TaiwanCorrespondence: Yung-Po LiawDepartment of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110, Sec. 1 Jianguo N. Road, Taichung City, 40201, TaiwanTel +886-4-24730022 ext.11838Fax +886-4-23248179Email Liawyp@csmu.edu.twYuan-Shiun ChangDepartment of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung, 40402, TaiwanTel +886-4-22053366 ext. 5502Fax +886-4-22083362Email yschang@mail.cmu.edu.twPurpose: We investigated the interactive effect of rs10506151 polymorphism of the Leucine-rich repeat kinase 2 (LRRK2) gene and type 2 diabetes (T2D) on neurodegenerative disease (ND) risk.Materials and Methods: Data of 17, 927 participants in the Taiwan Biobank (TWB) assessed between 2008 and 2015 were linked to healthcare records in the National Health Insurance Research Database (NHIRD). The odd ratios (ORs) and 95% confidence intervals (CIs) for NDs were determined using logistic regression analysis.Results: There were 145 cases with NDs, and 28.28% (n = 41) of these individuals had T2D. Associations of neurodegenerative disorders with LRRK2 rs10506151 variant and T2D were not significant. The corresponding ORs (95% CI) for NDs were 1.06 (0.75– 1.49) in CA/AA compared to CC individuals and 0.93 (0.63– 1.39) in those with T2D compared to non-diabetic participants. However, we found evidence of a significant interaction between rs10506151 and T2D (p = 0.0073). After stratification by genotypes of rs10506151, the OR for NDs was 0.37 (CI, 0.17– 0.82) in CA/AA individuals with T2D and 1.41 (0.88– 2.27) in their CC counterparts. When CA/AA individuals with T2D represented the reference group, the OR (95% CI) was 1.74 (0.81– 3.73) in CC individuals with no T2D, 2.47 (CI, 1.14– 5.38) in CA/AA individuals with no T2D, and 2.34 (CI, 1.07– 5.11) in CC individuals with T2D.Conclusion: Our data indicated that the risk of NDs was significantly lower among diabetic individuals with combined CA/AA of the LRRK2 rs10506151 variant in Taiwan.Keywords: polymorphism, neurodegenerative disorders, diabetes, variation

Yu-Shuan Chen,1–3 Yu-Han Chiu,3 Yuan-Sheng Li,3 En-Yi Lin,3,4 Dean-Kuo Hsieh,5 Chia-Hung Lee,3 Mao-Hsuan Huang,1 Hong-Meng Chuang,1 Shinn-Zong Lin,1,6 Horng-Jyh Harn,1,7,* Tzyy-Wen Chiou3,*1Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, Republic of China; 2Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, Republic of China; 3Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, Republic of China; 4Department of Chemistry, National Dong Hwa University, Hualien, Taiwan, Republic of China; 5Department and Graduate Institute of Applied Chemistry, Chaoyang University of Technology, Taichung, Taiwan, Republic of China; 6Department of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, Republic of China; 7Department of Pathology, Hualien Tzu Chi Hospital, Tzu Chi University, Hualien, Taiwan, Republic of China*These authors contributed equally to this workIntroduction: Kolliphor® EL (K-EL) is among the most useful surfactants in the preparation of emulsions. However, it is associated with low hydrophobic drug loading in the resulting emulsified formulation.Methods: In this study, a formulation for intranasal administration of butylidenephthalide (Bdph), a candidate drug against glioblastoma (GBM), was prepared. Physical characteristics of the formulation such as particle size, zeta potential, conductivity, and viscosity were assessed, as well as its cytotoxicity and permeability, in order to optimize the formulation and improve its drug loading capacity.Results: The optimized formulation involved the integration of polyethylene glycol 400 (PEG 400) in K-EL to encapsulate Bdph dissolved in dimethyl sulfoxide (DMSO), and it exhibited higher drug loading capacity and drug solubility in water than the old formulation, which did not contain PEG 400. Incorporation of PEG 400 as a co-surfactant increased Bdph loading capacity to up to 50% (v/v), even in formulations using Kolliphor® HS 15 (K-HS15) as a surfactant, which is less compatible with Bdph than K-EL. The optimized Bdph formulation presented 5- and 2.5-fold higher permeability and cytotoxicity, respectively, in human GBM than stock Bdph. This could be attributed to the high drug loading capacity and the high polarity index due to DMSO, which increases the compatibility between the drug and the cell. Rats bearing a brain glioma treated with 160 mg/kg intranasal emulsified Bdph had a mean survival of 37 days, which is the same survival time achieved by treatment with 320 mg/kg stock Bdph. This implies that the optimized emulsified formulation required only half the Bdph dose to achieve an efficacy similar to that of stock Bdph in the treatment of animals with malignant brain tumor.Keywords: glioblastoma, polyethylene glycol 400, butylidenephthalide, loading capacity, permeability, intranasal administration

Wei-Chieh Lin,1 Chang-Wen Chen,1 Chin-Li Lu,2,3 Wu-Wei Lai,4 Min-Hsin Huang,4 Liang-Miin Tsai,1 Chung-Yi Li,2,5,* Chao-Han Lai4,* 1Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Graduate Institute of Food Safety, College of Agriculture and Nature Resources, National Chung Hsing University, Taichung, Taiwan; 4Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan *These authors contributed equally to this work Purpose: COPD is associated with coronary artery disease, and exacerbations are major events in COPD. However, the impact of recent hospitalized exacerbations on outcomes of percutaneous coronary intervention (PCI) remains underdetermined. Patients and methods: Using the National Health Insurance Research Database of Taiwan, we identified 215,275 adult patients who underwent first-time PCI between 2000 and 2012. Among these patients, 15,485 patients had COPD. The risks of hospital mortality, overall mortality, and adverse cardiovascular outcomes after PCI (ie, ischemic events, repeat revascularization, cerebrovascular events, and major adverse cardiac and cerebrovascular events [MACCEs]) in relation to COPD, and the frequency and timing of recent hospitalized exacerbations within 1 year before PCI were estimated. Results: COPD was independently associated with increased risks of hospital mortality, overall mortality, ischemic events, cerebrovascular events, and MACCE during follow-up after PCI. Among cerebrovascular events, ischemic rather than hemorrhagic stroke was more likely to occur. In COPD patients, recent hospitalized exacerbations further increased the risks of overall mortality, ischemic events, and MACCE following PCI. Notably, patients with more frequent or more recent hospitalized exacerbations had a trend toward higher risks of these adverse events (all P-values for trend

Min H Huang, Tracy Shilling, Kara A Miller, Kristin Smith, Kayle LaVictoire Physical Therapy Department, School of Health Professions and Studies, University of Michigan–Flint, Flint, MI, USA Abstract: Older cancer survivors may be predisposed to falls because cancer-related sequelae affect virtually all body systems. The use of a history of falls, gait speed, and balance tests to assess fall risks remains to be investigated in this population. This study examined the relationship of previous falls, gait, and balance with falls in community-dwelling older cancer survivors. At the baseline, demographics, health information, and the history of falls in the past year were obtained through interviewing. Participants performed tests including gait speed, Balance Evaluation Systems Test, and short-version of Activities-specific Balance Confidence scale. Falls were tracked by mailing of monthly reports for 6 months. A “faller” was a person with ≥1 fall during follow-up. Univariate analyses, including independent sample t-tests and Fisher’s exact tests, compared baseline demographics, gait speed, and balance between fallers and non-fallers. For univariate analyses, Bonferroni correction was applied for multiple comparisons. Baseline variables with P

Wei-Lin Chen,1,2 Yun-Fen Peng,1,3 Sheng-Kuo Chiang,1 Ming-Hsi Huang1–3 1National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan; 2Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 3PhD Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung, Taiwan Abstract: A fluorescence-labeled bioresorbable polymer was prepared by a coupling reaction of poly(ethylene glycol)-polylactide (PEG-PLA) with carboxyl pyrene, using N,N’-diisopropylcarbodiimide/1-hydroxy-7-azabenzotriazole (DIC/HOAt) as a coupling agent and 4-dimethylaminopyridine (DMAP) as a catalyst. The obtained copolymer, termed PEG-PLA-pyrene, was characterized using various analytical techniques, such as gel permeation chromatography (GPC), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), proton nuclear magnetic resonance (1H-NMR), infrared spectroscopy (IR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), to identify the molecular structure and to monitor the thermal property changes before and after the reaction. The presence of a pyrene moiety at the end of polylactide (PLA) did not alter the crystallization ability of the poly(ethylene glycol) (PEG) blocks, indicating that the conjugate preserved the inherent thermal properties of PEG-PLA. However, the presence of PEG-PLA blocks strongly reduced the melting of pyrene, indicating that the thermal characteristics were sensitive to PEG-PLA incorporation. Regarding the physicochemical behavior in aqueous solution, a higher concentration of PEG-PLA-pyrene resulted in a higher ultraviolet-visible (UV-vis) absorbance and fluorescence emission intensity. This is of great interest for the use of this conjugate as a fluorescence probe to study the in vivo distribution as well as the internalization and intracellular localization of polymeric micelles. Keywords: bioresorbable polymer, fluorescence probe, pyrene, polymeric micelles, poly (ethylene glycol)-polylactide, PEG-PLA

The 2010Mw7.2ElMayor-Cucapah earthquake provides a unique target of postseismic study as deformation extends across several distinct geological provinces, including the coldMesozoic arc crust of the Peninsular Ranges and newly formed, hot, extending lithosphere within the Salton Trough. We use five years of global positioning system measurements to invert for afterslip and constrain a 3-D finite-element model that simulates viscoelastic relaxation. We find that afterslip cannot readily explain far-field displacements (more than 50 km from the epicentre). These displacements are best explained by viscoelastic relaxation of a horizontally and vertically heterogeneous lower crust and upper mantle. Lower viscosities beneath the Salton Trough compared to the Peninsular Ranges and other surrounding regions are consistent with inferred differences in the respective geotherms. Our inferred viscosity structure suggests that the depth of the Lithosphere/Asthenosphere Boundary (LAB) is ~65 km below the Peninsular Ranges and ~32 km beneath the Salton Trough. These depths are shallower than the corresponding seismic LAB. This suggests that the onset of partial melting in peridotite may control the depth to the base of the mechanical lithosphere. In contrast, the seismic LAB may correspond to an increase in the partial melt percentage associated with the change from a conductive to an adiabatic geotherm.

The 4 April 2010 Mw 7.2 El Mayor-Cucapah (EMC) earthquake in Baja, California, and Sonora, Mexico, had primarily right-lateral strike-slip motion and a minor normal-slip component. The surface rupture extended about 120 km in a NW-SE direction, west of the Cerro Prieto fault. Here we use geodetic measurements including near- to far-field GPS, interferometric synthetic aperture radar (InSAR), and subpixel offset measurements of radar and optical images to characterize the fault slip during the EMC event. We use dislocation inversion methods and determine an optimal nine-segment fault geometry, as well as a subfault slip distribution from the geodetic measurements. With systematic perturbation of the fault dip angles, randomly removing one geodetic data constraint, or different data combinations, we are able to explore the robustness of the inferred slip distribution along fault strike and depth. The model fitting residuals imply contributions of early postseismic deformation to the InSAR measurements as well as lateral heterogeneity in the crustal elastic structure between the Peninsular Ranges and the Salton Trough. We also find that with incorporation of near-field geodetic data and finer fault patch size, the shallow slip deficit is reduced in the EMC event by reductions in the level of smoothing. These results show that the outcomes of coseismic inversions can vary greatly depending on model parameterization and methodology.

Geodetically measured surface displacements are produced by a combination of underlying deformation processes acting at different spatial and temporal scales. A complete history of surface measurements in an area can help discriminate contributions from tectonic, hydrologic, and anthropogenic processes. In this study, we use Synthetic Aperture Radar (SAR) images of the active mountain front and adjacent coastal plain of southwestern Taiwan to generate time series of surface deformation from 1995 to 2001 and from 2005 to 2008 based on the InSAR small baseline method. The InSAR measurements agree well with LOS motions estimated from continuous GPS measurements of 3D displacements between 2006 and 2008. A significant range increase in line of sight (LOS) is dominated by land subsidence in the coastal area of western and southwestern Taiwan. Subsidence rates vary with annual periods and are highly correlated with seasonal precipitation, which are likely associated with groundwater recharge and withdrawal. The long-term deformation is dominated by long-term tectonic loading in SW Taiwan during the interseismic period of the earthquake cycle, including elastic strain along or continuous creep on the active faults. Our results show the ability of InSAR to reveal spatiotemporal crustal deformation in western Taiwan with high spatial resolution and accuracy, which is potentially important for evaluating seismic hazards.

Large PbS protruded cubes, edge- A nd corner-truncated cubes and octahedra, and perfect octahedra with sizes over 200 nm have been synthesized in aqueous solution. By using two surface oxide-free tungsten probes to contact a clean particle, these PbS nanocrystals displayed facet-dependent electrical conductivity behaviors. Both {110} and {100} faces are highly conductive at applied voltages beyond 4 V, but the {111} faces can remain nonconductive even at 5 V. An asymmetric I-V curve was recorded when electrical contacts were made simultaneously on the {110} and {111} facets of a truncated cube. A modified band diagram of PbS is constructed to account for the observed facet-dependent effect. Density of states plots for varying numbers of PbS surface planes show larger areas of conduction band electron occupancy for the (110) and (100) planes than that for the (111) planes at a layer thickness of 3.0-3.4 nm. The work represents that, for the first time, the facet-dependent electrical properties of an n-type semiconductor nanocrystal are directly probed. Facet-dependent electrical conductivity should be a general semiconductor property and can be exploited to fabricate single-nanocrystal operating electronic components.

Background: Acute appendicitis is the most common acute abdomen in general surgery. Show-Chwan Memorial Hospital began an AITS/IRCAD laparoscopic training program in late May 2008. In this retrospective analysis, we surveyed the impact of the AITS training program on surgeons' preference for open appendectomy (OA) versus laparoscopic appendectomy (LA).Methods: From January 1, 2004 to July 31, 2009, patients diagnosed with acute appendicitis in Changhua Show-Chwan Memorial Hospital and Chang-Bing Show-Chwan Memorial Hospital were retrospectively analyzed. Demographic data, laboratory examinations, surgical methods, hospital stay, and complication rate data were collected and analyzed. The LA rate and effect of surgeons' preference before and after AITS were compared.Results: In all, 1,267 patients (58.2% male and 41.8% female; mean age, 36.6 years) were diagnosed with acute appendicitis during this period. Among them, 78.9% of patients had uncomplicated and 21.1% complicated appendicitis; 784 patients (61.9%) underwent OA, and 465 (36.7%) received LA. In 2004, only 8.1% of patients underwent LA, but the number increased rapidly to 90.4% in 2009 (P < 0.001). The average LA rate before AITS was 21%; however, after AITS, the LA rate increased to 84.6% (P < 0.001). The LA rate increased for all surgeons completing the training course, ranging from 16 to 83%. The overall appendectomy complication rate was 8.4%, with no significant difference between OA (9.7%) and LA (6.5%; P = 0.174). Hospital stay was shorter in the LA group (4.05 ± 1.9 days) compared with the OA group (4.55 ± 3.6; P = 0.006).Conclusions: Attending the laparoscopic training course significantly increased surgeons' preference for LA. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic adrenalectomy offers distinct benefits to patients and has now become the gold standard for the removal of adrenal lesions. Nonetheless, the procedure poses a challenge for surgeons in regards to the maneuverability of instruments, the two-dimensional operating field and the counterintuitive movements. This study reports our experience using the Zeus robotic surgical system in laparoscopic adrenalectomy compared with traditional laparoscopic adrenalectomy.Patients and Methods: From January 2003 to February 2005, a total of 12 patients were prospectively enrolled to receive robot-assisted laparoscopic adrenalectomy (RALA) or traditional laparoscopic adrenalectomy (TLA). The time necessary for robotic setup and operation was recorded, as well as complications, technical problems, postoperative hospital stay, morbidity, and mortality.Results: Five RALA procedures and seven TLA were successfully completed. There was no significant difference between the groups in terms of age, body mass index, and tumor size. Resection times were longer in the RALA group (168.0 +/- 30.7 min vs. 131.4 +/- 29.0 min, p = 0.05). There were no perioperative complications. There was neither postoperative mortality nor morbidity at the time of discharge and during one year follow-up.Conclusions: RALA is as safe and technically feasible as TLA, It provides a real benefit for the surgeon with the three dimensional view, a comfortable sitting position, the elimination of the surgeon's tremor, and increased degrees of freedom of the operative instruments compared with TLA. However, patient outcomes and operative costs should be evaluated further. [ABSTRACT FROM AUTHOR]

Keloids result from pathological wound healing responses. However, the pathogenesis of keloids is still poorly understood. PGE2 was shown to decrease fibroblast proliferation, inhibit collagen synthesis and enhance the expression of matrix-metalloproteinases (MMPs). This study sought to delineate the production of PGE2 by normal and keloid-derived dermal fibroblasts. Human normal and keloid dermal fibroblasts were cultured in vitro. Cell proliferation and viability were determined based on WST-1 assay. IL-1beta-induced PGE2 production and effects of PGE2 on the synthesis of procollagen by culture-derived fibroblasts were determined by using enzyme-linked immunosorbant assay (ELISA) kits. IL-1beta-induced MMP-1 production by culture-derived fibroblasts was determined with an MMP-1 immunoassay kit. Our results showed that normal and keloid-derived fibroblasts exhibited a statistically significant increase (p<0.05) in cell proliferation when the cells were cultured in media with an increase in the concentrations (0%, 2% and 10%) of fetal bovine serum (FBS). In culture medium without FBS, an increase in cell proliferation of keloid-derived fibroblasts was detectable when compared with those of control fibroblasts. IL-1beta (1 ng/ml and 10 ng/ml) stimulated statistically significant production (p<0.01) of PGE2 by both normal and keloid-derived fibroblasts. However, lower levels of PGE2 produced by keloid-derived fibroblasts were detectable compared with those produced by normal-derived fibroblasts (p<0.05). In this study, although not statistically significant, inhibition of procollagen production by PGE2 in a dose-dependent manner was found. In addition, decreased production of MMP-1 by keloid-derived fibroblasts compared with those of control fibroblasts was also observed. In conclusion, keloid-derived fibroblasts produced less PGE2 than those produced by control fibroblasts. The role of diminished capacity of PGE2 production in keloid formation is presently unknown and needs further study. [ABSTRACT FROM AUTHOR]

Aim: Bipolar disorder (BD) and major depression have been associated with an increased risk of developing Parkinson's disease (PD); however, few studies have directly compared the risk of PD development between patients with BD and major depression while considering relevant risk factors and psychotropic medications., Methods: Using the Taiwan National Health Insurance Research Database, 21,186 patients with BD, 21,188 patients with major depression, and 42,374 controls were enrolled between 2001 and 2009, and followed until the end of 2011. Individuals who developed PD during the follow-up period were identified. Cox regression models were used to analyze the hazard ratio (HR) of developing PD, adjusting for demographic factors, comorbidities, and psychotropic medication usage., Results: Both patients with BD [HR 8.63, 95% confidence interval (CI) 6.35-11.72] and those with major depression (HR 5.68, 95% CI 4.15-7.78) had an elevated risk of subsequent PD compared to the controls. Patients with BD were associated with a 51% increased risk of subsequent PD compared with patients with major depression. Long-term treatment with antiepileptic mood stabilizers was associated with increased PD risk among patients with late-onset BD and high Charlson comorbidity index scores. Lithium was not associated with an increased PD risk., Conclusions: The study highlights an elevated PD risk in patients with BD and major depression compared to the controls, with BD patients at highest risk. Further research is needed to elucidate the complex interplay between psychotropic medications and neurodegenerative processes in BD, aiming to optimize therapeutic strategies and improve patient outcomes., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Strain WL0113 T was isolated from surface seawater of the coast of Lianyungang, Jiangsu province, PR China. Strain WL0113 T shared highest 16S rRNA gene sequence similarity with Roseobacter insulae YSTF-M11 T (98.8%), followed by R. cerasinus AI77 T (98.8%), R. ponti MM-7  T (98.0%). Strain WL0113 T was Gram-stain-negative, cream, aerobic, non-motile and coccoid- to oval-shaped, and able to grow at pH 6.5-9.0 (optimum, pH 7.0-8.0), at 10-37  °C (optimum, 28 °C) and in the presence of 1-5% (w/v; optimum, 2.5%) NaCl. Ubiquinone-10 was detected as dominant. The main fatty acids (> 5%) of the strain WL0113 T were C 16:0 , iso-C 17:0 3OH, C 20:4 ω6,9,12,15c (arachidonic acid), and summed feature 8 (C 18:1 ω7c and/or C 18:1 ω6c). The major polar lipids include phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, glycophospholipid, unknown aminolipid, unknown phospholipid, and two unknown polar lipids. The ANI and dDDH values between strain WL0113 T and Roseobacter cerasinus were 80.4% and 23.0%, respectively. The genomic DNA G + C content of strain WL0113 T was 63.1%. Based on these data, it is proposed that strain WL0113 T represent novel species of the genus Roseobacter, for which the name Roseobacter sinensis sp. nov. is proposed. The type strain is WL0113 T (= GDMCC 1.3082 T  = JCM 35567 T )., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Atypical teratoid rhabdoid tumor (ATRT) is an aggressive brain tumor that mainly affects young children. Our recent study reported a promising therapeutic strategy to trigger DNA damage, impede homologous recombination repair, and induce apoptosis in ATRT cells by targeting ribonucleotide reductase regulatory subunit M2 (RRM2). COH29, an inhibitor of RRM2, effectively reduced tumor growth and prolonged survival in vivo. Herein, we explored the underlying mechanisms controlling these functions to improve the clinical applicability of COH29 in ATRT., Methods: Molecular profiling of ATRT patients and COH29-treated cells was analyzed to identify the specific signaling pathways, followed by validation using a knockdown system, flow cytometry, q-PCR, and western blot., Results: Elevated E2F1 and its signaling pathway were correlated with poor prognosis. RRM2 inhibition induced DNA damage and activated ATM, which reduced Rb phosphorylation to promote Rb-E2F1 interaction and hindered E2F1 functions. E2F1 activity suppression led to decreased E2F1-dependent target expressions, causing cell cycle arrest in the G1 phase, decreased S phase cells, and blocked DNA damage repair., Conclusion: Our study highlights the role of ATM/Rb/E2F1 pathway in controlling cell cycle arrest and apoptosis in response to RRM2 inhibition-induced DNA damage. This provides insight into the therapeutic benefits of COH29 and suggests targeting this pathway as a potential treatment for ATRT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Exposure to multiple metals may cause adverse effects, particularly in the kidneys. However, studies on the combined and interaction effects of metal mixtures on human health remain limited., Objective: The study aims to evaluate the interaction between metals and assess the combined effects of exposure to metal mixtures on tumor necrosis factor-alpha (TNF-α) levels and kidney function METHODS: Particular emphasis has been placed on the impact of various metals, including arsenic (As), cadmium (Cd), lead (Pb), as well as essential trace elements, such as cobalt (Co), copper (Cu), selenium (Se), and zinc (Zn), on human health and their potential collective influence on both TNF-α and kidney function. This cross-sectional study analyzed the data of 421 adults who underwent a health examination. Generalized linear model (GLM), Bayesian kernel machine regression (BKMR), and quantile-based G-computation (qgcomp) were used to evaluate the association and joint effects between the metals and TNF-α, as well as kidney function., Results: Increased concentrations of As (β = 0.11, 95 % CI = 0.05, 0.17) and Pb (β = 0.30, 95 % CI = 0.23, 0.37) in the blood were associated with elevated levels of TNF-α, while elevated Cu (β = -0.42, 95 % CI = -0.77, -0.07) levels were linked to a significant reduction in TNF-α. The overall effect of metals mixture showed a significant association with a decline in eGFR and an increase TNF-α in the BKMR model. Qgcomp analysis of the metals mixture (β = -0.06, 95 % CI = -0.07, -0.05) indicated that As, Pb, and Zn were the primary contributors to the reduction in eGFR, while As and Pb were the major contributors in metals mixture (β = 0.12, 95 % CI = 0.08, 0.15) to the elevation of TNF-α levels., Conclusion: Exposure to multiple metals could have joint association with the TNF-α levels and kidney function. Furthermore, TNF-α could act as a mediator between metal mixtures and eGFR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Purpose: Biliary tract cancers (BTCs) harbor an immunosuppressed tumor microenvironment and respond poorly to PD-1/PD-L1 inhibitors. Bevacizumab (anti-vascular endothelial growth factor) plus chemotherapy can promote anticancer immunity, augmenting response to PD-L1 inhibition., Patients and Methods: This randomized, double-blind, proof-of-concept phase II study enrolled patients (n = 162) with previously untreated advanced BTC (IMbrave151; ClinicalTrials.gov identifier: NCT04677504). Patients were randomly assigned 1:1 to receive cycles of atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) or atezolizumab plus placebo once every 3 weeks until disease progression or unacceptable toxicity. All patients received cisplatin (25 mg/m 2 ) plus gemcitabine (1,000 mg/m 2 ; cisplatin plus gemcitabine [CisGem]) on days 1 and 8 once every 3 weeks for up to eight cycles. Stratification of patients was by disease status, geographic region, and primary tumor location. The primary end point was progression-free survival (PFS). No formal hypothesis testing was performed. Exploratory correlative biomarker analysis was undertaken using transcriptome analysis (n = 95) and mutation profiling (n = 102) on baseline tumor samples., Results: Between February and September 2021, 162 patients were enrolled. Median PFS was 8.3 months in the bevacizumab arm and 7.9 months in the placebo arm (stratified hazard ratio [HR], 0.67 [95% CI, 0.46 to 0.95]). Median overall survival (OS) was 14.9 and 14.6 months in the bevacizumab and placebo arms, respectively (stratified HR, 0.97 [95% CI, 0.64 to 1.47]). The incidence of grade 3 or 4 adverse events was 74% in both arms. High VEGFA gene expression was associated with improved PFS (HR, 0.44 [95% CI, 0.23 to 0.83]) in the bevacizumab arm versus placebo., Conclusion: In unselected patients with advanced BTC, adding bevacizumab to atezolizumab plus CisGem modestly improves PFS but not OS. High VEGFA gene expression may represent a predictive biomarker of benefit from atezolizumab/bevacizumab, warranting further investigation.

Background: Barcode information management systems (BIMS) have been implemented in operating rooms to improve the quality of medical care and administrative efficiency. Previous research has demonstrated that the Agile development model is extensively used in the development and management of information systems. However, the effect of information systems on staff acceptance has not been examined within the context of clinical medical information management systems., Objective: This study aimed to explore the effects and acceptance of implementing a BIMS in comparison to the original information system (OIS) among operating and supply room staff., Methods: This study was a comparative cohort design. A total of 80 staff members from the operating and supply rooms of a Northern Taiwan medical center were recruited. Data collection, conducted from January 2020 to August 2020 using a mobile-based structured questionnaire, included participant characteristics and the Information Management System Scale. SPSS (version 20.0, IBM Corp) for Windows (Microsoft Corporation) was used for data analysis. Descriptive statistics included mean, SD, frequency, and percentage. Differences between groups were analyzed using the Mann-Whitney U test and Kruskal-Wallis test, with a P value <.05 considered statistically significant., Results: The results indicated that the BIMS generally achieved higher scores in key elements of system success, system quality, information quality, perceived system use, perceived ease of use, perceived usefulness, and overall quality score; none of these differences were statistically significant (P>.05), with the system quality subscale being closest to significance (P=.06). Nurses showed significantly better perceived system use than technicians (1.58, SD 4.78 vs -1.19, SD 6.24; P=.02). Significant differences in perceived usefulness were found based on educational level (P=.04) and experience with OIS (P=.03), with junior college-educated nurses and those with over 6 years of OIS experience reporting the highest perceived usefulness., Conclusions: The study demonstrates that using the Agile development model for BIMS is advantageous for clinical environments. The high acceptance among operating room staff underscores its practicality and broader adoption potential. It advocates for continued exploration of technology-driven solutions to enhance health care delivery and optimize clinical workflows., (©Chia-Yen Li, Mei-Hui Huang, Yu-Shiue Lin, Chi-Ming Chu, Hsueh-Hsing Pan. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 17.10.2024.)

A Gram-staining negative, non-motile, rod-shaped, oxidase negative and catalase positive strain WL0021 T was isolated from cricket (Gryllus chinensis) living in the campus of Hohai University. Strain WL0021 T was characterized utilizing a polyphasic taxonomy approach. The major fatty acids (> 5%) for strain WL0021 T were C 16:0 and summed feature 8, and the major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, phospholipid, two aminolipids, and an unidentified polar lipid. Ubiquinone-10 was detected as the predominant respiratory quinone. The results of 16S rRNA gene phylogenetic analyses revealed that strain WL0021 T had the highest sequence similarity of 95.3% to Microvirga flavescens c27j1 T and strain WL0021 T formed a distinct linage within the family Methylobacteriaceae in the phylogenetic trees. Whole genomic DNA G+C content was 48.3%. Combined with the results from this study, strain WL0021 T should represent a novel genus in the family Methylobacteriaceae, for which the name Hohaiivirga grylli gen. nov., sp. nov. (type strain WL0021 T =GDMCC 1.2420 T  =JCM 34655 T =MCCC 1K05886 T ) is proposed., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background. The interplay among human gut microbiota (GM) composition, osteoarthritis (OA) and OA-related medication use has been extensively discussed. However, to date, there has been no exploration of the genetic correlation among these three factors. Hypothesis/Gap. The potential causal link between GM and OA), and whether medications influence this relationship, remains unclear. Methods. We utilized bidirectional Mendelian randomization (MR) to explore the genetic associations between GM and OA. We leveraged genome-wide association study (GWAS) summary statistics from the MiBioGen and GO consortia, which provided data on GM taxa and OA cases, respectively. We identified outlier single-nucleotide polymorphisms using radial-MR and assessed causal associations using inverse variance weighting (IVW), weighted median and MR-Egger methods. Robust outcomes, consistent across these methods, were reported. We addressed potential biases through tests for horizontal pleiotropy and heterogeneity, supplemented by the Mendelian randomization pleiotropy residual sum and outlier method. Multivariable MR techniques were applied to adjust for OA medication use using UK Biobank data. Results. IVW estimates revealed a significant increase in hip OA risk for Gordonibacter and Eubacterium (brachy group) [odds ratio (OR): 1.09, 95% confidence interval (CI): 1.04-1.15, P =7.82E-04; OR: 1.09, 95% CI: 1.03-1.16, P =4.67E-03, respectively]. Conversely, Senegalimassilia , Slackia and Streptococcus exhibited protective effects (OR: 0.88, P =2.14E-02; OR: 0.88, P =3.33E-02; 0.91, P =4.29E-02). Sutterella increased the risk of knee OA (OR=1.15, 95% CI: 1.07-1.25, P =4.06E-04), while Haemophilus decreased it (OR=0.94, 95% CI: 0.88-1.00, P =4.26E-02). No significant heterogeneity or horizontal pleiotropy was observed in the results. Even after accounting for the potential confounding effect of medication, the results remained consistent. No reverse causation was detected. Conclusions. Our MR study reveals gut microbiome links to OA risk. Associations hold after adjusting for medication, indicating a potential causal connection between GM and OA.

Two Gram-stain-negative, aerobic, ovoid to short rod-shaped bacterial strains, designated as WL0062 T and WL0115, were isolated from coastal zone of the Yellow Sea, Jiangsu Province, PR China, respectively. Strain WL0062 T grew optimally at 28 °C, pH 7.0-8.0 and with 1.0-3.0% (w/v) NaCl. Strain WL0115 grew optimally at 28 °C, pH 6.0-7.0 and with 1.0-3.0% (w/v) NaCl. In the bac120 tree, strains WL0062 T and WL0115 clustered together with Sedimentimonas flavescens B57 T . The respiratory quinone of both strains was ubiquinone-10. The major polar lipids of both strains were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, glycolipid, phosphatidylmonomethylethanolamine, and one unidentified polar lipid. The major fatty acids of strain WL0062 T were summed features 8 (C 18 : 1  ω 6 c and/or C 18 : 1  ω 7 c ). The major fatty acids of strain WL0115 were summed features 8 (C 18 : 1  ω 6 c and/or C 18 : 1  ω 7 c ), C 18 : 0 , iso-C 17 : 1  ω 5 c and C 20 : 4  ω 6/9/12/15 c (arachidonic acid). The G+C content of genomic DNA of strains WL0062 T and WL0115 was 64.0 mol% in both of them. Combined with the analysis of average nucleotide identity, average amino acid identity, and digital DNA-DNA hybridization, strain WL0062 T represents a novel species of the genus Rhodobacter , for which the name Rhodobacter flavimaris sp. nov is proposed. The type strain is WL0062 T (=MCCC 1K06014 T =JCM 34676 T =GDMCC 1.2427 T ). Strain WL0115 (=MCCC 1K07531=JCM 35568=GDMCC 1.3088) should belong to the same species as Sedimentimonas flavescens B57 T . In addition, on the basis of phylogenomic relationship and phenotypical characteristics, the genera Paenirhodobacter , Sedimentimonas , and Sinirhodobacter are proposed as synonyms of Rhodobacter .

Purpose: Screening for nasopharyngeal carcinoma (NPC) has shown an improvement in early detection and survival rates of NPC in endemic regions. It is critical to evaluate whether NPC screening can reduce NPC-specific mortality in the population., Methods: Sixteen towns in Sihui and Zhongshan cities, China, were selected; eight were randomly allocated to the screening group and eight to the control group. Residents age 30-69 years with no history of NPC were included from January 1, 2008, to December 31, 2015. Residents in the screening towns were invited to undergo serum Epstein-Barr virus (EBV) viral capsid antigen/nuclear antigen 1-immunoglobulin A antibody tests; others received no intervention. The population was followed until December 31, 2019. Nonparametric tests and Poisson regression models were used to estimate the screening effect on NPC mortality, accounting for the cluster-randomized design. The trial is registered with ClinicalTrials.gov (identifier: NCT00941538)., Results: A total of 174,943 residents in the screening group and 186,263 residents in the control group were included. NPC incidence and overall mortality were similar between the two groups. A total of 52,498 (30.0% of 174,943) residents participated in the serum EBV antibody test. The overall compliance rate for endoscopic examination and/or biopsies among baseline and ever-classified high-risk participants was 65.9% (1,110 of 1,685) and 67.6% (1,703 of 2,518), respectively. A significant 30% reduction in NPC mortality was observed in the screening group compared with the control group (standardized NPC-specific mortality rate of 8.2 NPC deaths per 1,000 person-years versus 12.5; adjusted rate ratio [RR], 0.70 [95% CI, 0.49 to 0.997]; P = .048). This benefit was most evident among individuals age 50 years and older (RR, 0.56 [95% CI, 0.37 to 0.85]; P = .007) compared with those younger than 50 years (RR, 0.96 [95% CI, 0.64 to 1.46]; P = .856)., Conclusion: In this 12-year trial, EBV antibody testing resulted in a significant reduction in NPC mortality.

In this work, we investigate, for the first time, a low phase noise and wide tuning range voltage-controlled surface acoustic wave oscillator (VCSO) based on a lithium niobate on sapphire (LNOS) low-loss acoustic delay line (ADL). The thin-film LN/SiO2 bilayer acoustic waveguide, together with the single-phase unidirectional transducer (SPUDT) design, is key to attaining low insertion loss (IL) by enhancing energy confinement and directionality. Based on a high-performance ADL with an IL of only 5.2 dB, a fractional bandwidth (FBW) of 5.38%, and a group delay of 110 ns, the VCSO is implemented by commercially available circuit components using a series-resonant topology. The LNOS ADL oscillator operates at 888 MHz, showcasing a low phase noise of -94.1 dBc/Hz at 1-kHz offset and a root-mean-square (rms) jitter of only 30.26 fs (integrated from 12 kHz to 20 MHz) while only consuming 16 mA of supply current. Featuring a wide frequency tuning range of 6630 ppm, the proposed VCSO is a promising low-noise, low-power, and high-frequency timing device for emerging applications.Index Terms- Acoustic delay line (ADL), jitter, lithium niobate (LN), oscillator, phase noise, surface acoustic wave (SAW), thin film.skiptabldblfloatfix.

By primarily adjusting the reagent amounts, particularly the volume of AgNO 3 solution introduced, Ag 2 O cubes with decreasing sizes from 440 to 79 nm, octahedra from 714 to 106 nm, and rhombic dodecahedra from 644 to 168 nm are synthesized. 733 nm cuboctahedra are also prepared for structural analysis. With in-house X-ray diffraction (XRD) peak calibration, shape-related peak shifts are recognizable. Synchrotron XRD measurements at 100 K reveal the presence of bulk and surface layer lattices. Bulk cell constants also deviate slightly. They show a negative thermal expansion behavior with shrinking cell constants at higher temperatures. The Ag 2 O crystals exhibit size- and facet-dependent optical properties. Bandgaps red-shift continuously with increasing particle sizes. Optical facet effect is also observable. Moreover, synchrotron XRD peaks of a mixture of Cu 2 O rhombicuboctahedra and edge- and corner-truncated cubes exposing all three crystal faces can be deconvoluted into three components with the bulk and the [111] microstrain phase as the major component. Interestingly, while the unheated Cu 2 O sample shows clear diffraction peak asymmetry, annealing the sample to 450 K yields nearly symmetric peaks even when returning the sample to room temperature, meaning even moderately high temperatures can permanently change the crystal lattice., (© 2024 Wiley‐VCH GmbH.)

The need for wideband radio frequency front ends (RFFEs) with next-generation wireless protocols highlights the importance of electromechanical coupling [Formula: see text]. The hetero acoustic layered (HAL) surface acoustic wave (SAW) resonator with aluminum (Al) electrodes has shown superior performance compared to conventional SAW devices. Despite gold (Au) having excellent conductivity and stable properties, its high acoustic absorption and low phase velocity have made it less favorable for electrodes. This work demonstrates that high-performance shear horizontal (SH)-SAW resonators can be fabricated on the lithium niobate-on-insulator (LNOI) platform using a setup specifically designed for an Au electrodes. Experimental validation shows that the device achieves a high quality factor (Q) over 870, excellent [Formula: see text] up to 40%, and operates around 765 MHz. Unwanted transverse spurious modes are suppressed through adequate electrode design, and the temperature stability of LNOI SH-SAW with Au electrodes is discussed. This study highlights gold's potential as an electrode material for high [Formula: see text], clean spectrum, and wideband applications.