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We analyze the transmission characteristics of a Sagnac loop interferometer containing a polarization-dependent loss element and lossless polarization-converting elements by use of Jones matrices. We show that polarization independence in the transmission mode can be achieved in such a configuration and that maximum transmittance occurs when a half-wave plate is used for the polarization-converting element. The result is verified experimentally for a fiber acousto-optic tunable filter and cascaded long-period fiber gratings with either intrinsic or process-induced polarization-dependent filtering characteristics.

We describe a novel scheme for complete suppression of polarization-dependent loss/gain (PDL, PDG) for transmission-type optical devices (LPG, SOA) via a l/2-shifted all-fiber Sagnac loop interferometer. The results are explained theoretically and demonstrated experimentally. © 2004 Optical Society of America.

Vivian Juang,1 Hsin-Pin Lee,2 Anya Maan-Yuh Lin,1,3 Yu-Li Lo1 1Department and Institute of Pharmacology, National Yang-Ming University, 2Department of Biological Sciences and Technology, National University of Tainan, 3Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China Abstract: Antimicrobial peptides (AMPs) have been recently evaluated as a new generation of adjuvants in cancer chemotherapy. In this study, we designed PEGylated liposomes encapsulating epirubicin as an antineoplastic agent and tilapia hepcidin 2–3, an AMP, as a multidrug resistance (MDR) transporter suppressor and an apoptosis/autophagy modulator in human cervical cancer HeLa cells. Cotreatment of HeLa cells with PEGylated liposomal formulation of epirubicin and hepcidin 2–3 significantly increased the cytotoxicity of epirubicin. The liposomal formulations of epirubicin and/or hepcidin 2–3 were found to noticeably escalate the intracellular H2O2 and O2- levels of cancer cells. Furthermore, these treatments considerably reduced the mRNA expressions of MDR protein 1, MDR-associated protein (MRP) 1, and MRP2. The addition of hepcidin 2–3 in liposomes was shown to markedly enhance the intracellular epirubicin uptake and mainly localized into the nucleus. Moreover, this formulation was also found to trigger apoptosis and autophagy in HeLa cells, as validated by significant increases in the expressions of cleaved poly ADP ribose polymerase, caspase-3, caspase-9, and light chain 3 (LC3)-II, as well as a decrease in mitochondrial membrane potential. The apoptosis induction was also confirmed by the rise in sub-G1 phase of cell cycle assay and apoptosis percentage of annexin V/propidium iodide assay. We found that liposomal epirubicin and hepcidin 2–3 augmented the accumulation of GFP-LC3 puncta as amplified by chloroquine, implying the involvement of autophagy. Interestingly, the partial inhibition of necroptosis and the epithelial–mesenchymal transition by this combination was also verified. Altogether, our results provide evidence that coincubation with PEGylated liposomes of hepcidin 2–3 and epirubicin caused programmed cell death in cervical cancer cells through modulation of multiple signaling pathways, including MDR transporters, apoptosis, autophagy, and/or necroptosis. Thus, this formulation may provide a new platform for the combined treatment of traditional chemotherapy and hepcidin 2–3 as a new adjuvant for effective MDR reversal. Keywords: multidrug resistance, liposomes, antimicrobial peptide, epirubicin, apoptosis, autophagy

Abstract Nanometric cutting involves materials removal and deformation evolution in the surface at nanometer scale. At this length scale, atomistic simulation is a very useful tool to study the cutting process. In this study, large-scale molecular dynamics (MD) simulations with the model size up to 10 millions atoms have been performed to study three-dimensional nanometric cutting of copper. The EAM potential and Morse potential are used, respectively, to compute the interaction between workpiece atoms and the interactions between workpiece atoms and tool atoms. The material behavior, surface and subsurface deformation, dislocation movement, and cutting forces during the cutting processes are studied. We show that the MD simulation model of nanometric cutting has to be large enough to eliminate the boundary effect. Moreover, the cutting speed and the cutting depth have to be considered in determining a suitable model size for the MD simulations. We have observed that the nanometric cutting process is accompanied with complex material deformation, dislocation formation, and movement. We find that as the cutting depth decreases, the tangential cutting force decreases faster than the normal cutting force. The simulation results reveal that as the cutting depth decreases, the specific cutting force increases, i.e., “size effect” exists in nanometric cutting.

Background: Chinese females are distinguished internationally as having relatively high lung cancer incidence rates despite a low prevalence of cigarette smoking. In Singapore, this population comprises several dialect groups which have origins in different regions in China, each with its own traditional cultural practices.Methods: An analysis of 4029 incident cases of the disease notified to the Singapore Cancer Registry for 1968-1992 was undertaken to provide some insight into important aetiologic factors among these women.Results: The age-standardized incidence rate of lung cancer rose from 17.3 per 100,000 woman-years in 1968-1972 to 23.0 in 1978-1982 before falling off in more recent years. Age-period-cohort analysis indicated significant period and birth cohort effects, with the risk being highest for women born around 1908. Between the major dialect groups, Cantonese women had a significantly high rate compared with Hokkiens (relative risk [RR] = 2.6, 95% CI: 2.4-2.8). Histologically, there appears to be an increase in the proportion of adenocarcinomas diagnosed over this period (25.8% in 1968-1972 to 51.3% in 1988-1992).Conclusion: Our results suggest that traditional practices which have decreased over the years, and are more prominent among Southern Chinese, may play a part in the aetiology of lung cancer locally. [ABSTRACT FROM AUTHOR]

Objectives: To quantify the improvement in health outcomes in patients after total knee replacement (TKR).Methods: This was a two-year non-randomized prospective observational study in knee osteoarthritis (OA) patients undergone TKR. Patients were interviewed one week before, six months after, and two years after surgery using a standardized questionnaire including the SF-36, the Oxford Knee Score (OKS), and the Knee Society Clinical Rating Scale (KSS). A generalized estimating equation (GEE) model was used to estimate the magnitudes of the changes with and without the adjustment of age, ethnicity, BMI, and years with OA.Results: A total of 298 (at baseline), 176 (at six-months), and 111 (at two-years) eligible patients were included in the analyses. All the scores changed significantly over time, with the exception of SF-36 social functioning, vitality, and mental health. With the adjustment of covariates, the magnitude of changes in these scores was similar to those without the adjustment.Conclusions: Both general and knee-specific physical functioning had been significantly improved after TKR, while other health domains have not been substantially improved after the surgery. [ABSTRACT FROM AUTHOR]

Abstract: The multicenter, prospective phase 2 Australasian Leukaemia & Lymphoma Group NHL29 trial was conducted to assess the addition of ibrutinib to R-mini-CHOP (dose attenuated R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients aged ≥75 years with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Treatment consisted of six 21-day cycles of ibrutinib-R-mini-CHOP followed by two 21-day cycles of R-ibrutinib. Coprimary end points were deliverability and 2-year overall survival (OS). The median average relative total dose and average relative dose intensity for the entire regimen were both 97% (interquartile range, 82-100 and 88-100, respectively). With a median follow-up of 35.5 months, the 2-year OS was 68% (95% confidence interval [CI], 55.6-77.4) with a 2-year progression-free survival (PFS) of 60.0% (95% CI, 47.7-70.3). Median OS and PFS were 72 months (95% CI, 35 to not reached) and 40 months (95% CI, 20.4 to not reached), respectively. The overall response rate was 76% (61/79) of patients, with a complete response rate of 71% (56/79). Deaths occurred in 34 of 79 patients (43%), including 17 from progressive disease and 5 treatment related. Overall, 67% patients experienced at least 1 serious adverse event. Most common adverse events were infections and diarrhea (the majority grade 1-2). In both health-related quality of life measures, there was an improvement in functional and symptom scales, median health state classification score, and median visual analogue scale in responders over time. In conclusion, this study showed that the addition of ibrutinib to R-mini-CHOP was both deliverable and efficacious in elderly DLBCL patients., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Glaucoma is identified by the loss of retinal ganglion cells (RGCs). The primary approach to managing glaucoma is to control intraocular pressure (IOP). Lately, there has been an increasing focus on neuroprotective therapies for glaucoma because of the limited effectiveness of standard methods in reducing IOP and preventing ongoing vision deterioration in certain glaucoma patients. Various drug-based techniques with neuroprotective properties have demonstrated the ability to decrease the mortality of retinal ganglion cells. This study will analyze the currently recommended drug-based techniques for neuroprotection in the prospective treatment of glaucoma.

The finished precision rolling bearings after processing are required to pass the life test before they can be put into the market. The life testing takes a lot of time and expense. Aiming to solve the problem of time and expense, the 1D-CNN and 1D-CNN-LSTM hybrid neural networks are used for deep learning based on the existing rolling bearing life big data results (a total of 791152 date). Taking the wear of bearing as the target, the life prediction of bearing is carried out by using Python. The results show that: (1) 1D-CNN-LSTM algorithm and "all parameters" are selected as the best prediction options. (2) "XYZ direction displacement" and "all parameters" have the best fitting effect on the predicted wear value, and the MAPE is 4.18877, 1.2102, 2.68903 and 1.19981, respectively. The 1D-CNN-LSTM algorithm is slightly better than the 1D-CNN algorithm. (3) Using 1D-CNN-LSTM algorithm and "all parameters" to predict the bearing wear life will obtain good results. Compared with the highest 1D-CNN and "Four Bearing Temperatures" parameters, it is reduced by 14.7 times. (4) The prediction process and results provide a wear prediction method for relevant bearing enterprises in the experimental running-in stage. It can also provide reliable research ideas for subsequent related enterprises and scholars., Competing Interests: 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., (© 2024 Published by Elsevier Ltd.)

To investigate long-term outcomes and develop a risk model for pathological multi-station N2 (pN2b) in patients who underwent upfront surgery for clinical single-station N2 (cN2a) non-small cell lung cancer (NSCLC). From 2006 to 2018, 547 patients who had upfront surgery for suspected cN2a NSCLC underwent analysis. A risk model for predicting pN2b metastasis was developed using preoperative clinical variables via multivariable logistic analysis. Among 547 clinical cN2a NSCLC patients, 118 (21.6%), 58 (10.6%), and 371 (67.8%) had pN0, pN1, and pN2. Among 371 pN2 NSCLC patients, 77 (20.8%), 165 (44.5%), and 129 (34.7%) had pN2a1, pN2a2, and pN2b. The 5-year overall survival rates for pN2a1 and pN2a2 were significantly higher than for pN2b (p = 0.041). Histologic type (p < 0.001), age ≤ 50 years (p < 0.001), preoperatively confirmed N2 metastasis (p < 0.001), and clinical stage IIIB (vs. IIIA) (p = 0.003) were independent risk factors for pN2b metastasis. The risk scoring system based on this model demonstrated good discriminant ability for pN2b disease (area under receiver operating characteristic: 0.779). In cN2a NSCLC patients, those with multiple N2 metastases indicate worse prognosis than those with a single N2 metastasis. Our risk scoring system effectively predicts pN2b in these patients., (© 2024. The Author(s).)

This manuscript offers a concise overview of paper microfluidics, emphasizing its sustainable sensing applications in healthcare, environmental monitoring, and food safety. Researchers have developed innovative sensing platforms for detecting pathogens, pollutants, and contaminants by leveraging the paper's unique properties, such as biodegradability and affordability. These portable, low-cost sensors facilitate rapid diagnostics and on-site analysis, making them invaluable tools for resource-limited settings. This review discusses the fabrication techniques, principles, and applications of paper microfluidics, showcasing its potential to address pressing challenges and enhance human health and environmental sustainability.

Glaucoma, a leading cause of irreversible blindness, poses a significant global health burden. Early detection is crucial for effective management and prevention of vision loss. This study presents a collection of novel structural biomarkers in glaucoma diagnosis. By employing advanced imaging techniques and data analysis algorithms, we now can recognize indicators of glaucomatous progression. Many research studies have revealed a correlation between the structural changes in the eye or brain, particularly in the optic nerve head and retinal nerve fiber layer, and the progression of glaucoma. These biomarkers demonstrate value in distinguishing glaucomatous eyes from healthy ones, even in the early stages of the disease. By facilitating timely detection and monitoring, they hold the potential to mitigate vision impairment and improve patient outcomes. This study marks an advancement in the field of glaucoma, offering a promising avenue for enhancing the diagnosis and possible management.

Abstract: The phase 3 ASPEN trial (NCT03053440) compared Bruton tyrosine kinase inhibitors (BTKis), zanubrutinib and ibrutinib, in patients with Waldenström macroglobulinemia (WM). Post-hoc biomarker analysis was performed using next-generation sequencing on pretreatment bone marrow samples from 98 patients treated with zanubrutinib and 92 patients treated with ibrutinib with mutated (MUT) MYD88 and 20 patients with wild-type (WT) MYD88 treated with zanubrutinib. Of 329 mutations in 52 genes, mutations in CXCR4 (25.7%), TP53 (24.8%), ARID1A (15.7%), and TERT (9.0%) were most common. TP53MUT, ARID1AMUT, and TERTMUT were associated with higher rates of CXCR4MUT (P < .05). Patients with CXCR4MUT (frameshift or nonsense [NS] mutations) had lower very good partial response (VGPR) and complete response rates (CR; 17.0% vs 37.2%, P = .020) and longer time to response (11.1 vs 8.4 months) than patients with CXCR4WT treated with BTKis. CXCR4NS was associated with inferior progression-free survival (PFS; hazard ratio [HR], 3.39; P = .017) in patients treated with ibrutinib but not in those treated with zanubrutinib (HR, 0.67; P = .598), but VGPR + CR rates were similar between treatment groups (14.3% vs 15.4%). Compared with ibrutinib, patients with CXCR4NS treated with zanubrutinib had a favorable major response rate (MRR; 85.7% vs 53.8%; P = .09) and PFS (HR, 0.30; P = .093). In patients with TP53MUT, significantly lower MRRs were observed for patients treated with ibrutinib (63.6% vs 85.7%; P = .04) but not for those treated with zanubrutinib (80.8% vs 81.9%; P = .978). In TP53MUT, compared with ibrutinib, patients treated with zanubrutinib had higher VGPR and CR (34.6% vs 13.6%; P < .05), numerically improved MRR (80.8% vs 63.6%; P = .11), and longer PFS (not reached vs 44.2 months; HR, 0.66; P = .37). Collectively, patients with WM with CXCR4MUT or TP53MUT had worse prognosis compared with patients with WT alleles, and zanubrutinib led to better clinical outcomes., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Fully considering the mechanical and photoelastic anisotropies of monocrystalline silicon, the impacts of spatial symmetries on the stimulated Brillouin scatterings (SBSs) in nanoscale suspended silicon waveguides are studied theoretically and numerically based on group theory. First, starting from an assumption that the principal material coordinate system can be arbitrarily orientated in a waveguide with fixed geometry, the silicon waveguides are systematically classified into a number of point groups according to their spatial symmetry features. Thereafter, the symmetry characteristics of physical fields and SBS opto-mechanical coupling characteristics in the silicon waveguides belonging to different point groups are further examined, and the major new findings can be summarized as follows: The SBS opto-mechanical couplings in several kinds of silicon waveguides with certain nontrivial symmetry features exhibit relatively predictable behaviors in that the opto-mechanical coupling coefficients can be deterministically vanishing or nonvanishing under very few constraints, which can thus serve as general symmetry selection rules for SBSs in suspended silicon waveguides. The results obtained in the present study could be a useful theoretical reference for the design of novel SBS-active silicon photonic devices.

Background: Recently, plant-derived exosome-like nanoparticles (PDENs) have been isolated, and active research was focusing on understanding their properties and functions. In this study, the characteristics and molecular properties of ginseng root-derived exosome-like nanoparticles (GrDENs) were examined in terms of skin protection., Methods: HPLC-MS protocols were used to analyze the ginsenoside contents in GrDENs. To investigate the beneficial effect of GrDENs on skin, HaCaT cells were pre-treated with GrDENs (0-2 × 10 9 particles/mL), and followed by UVB irradiation or H 2 O 2 exposure. In addition, the antioxidant activity of GrDENs was measured using a fluorescence microscope or flow cytometry. Finally, molecular mechanisms were examined with immunoblotting analysis., Results: GrDENs contained detectable levels of ginsenosides (Re, Rg1, Rb1, Rf, Rg2 ( S ), Gyp17, Rd, C-Mc1, C-O, and F2). In UVB-irradiated HaCaT cells, GrDENs protected cells from death and reduced ROS production. GrDENs downregulated the mRNA expression of proapoptotic genes, including BAX, caspase-1, -3, -6, -7, and -8 and the ratio of cleaved caspase-8, -9, and -3 in a dose-dependent manner. In addition, GrDENs reduced the mRNA levels of aging-related genes (MMP2 and 3), proinflammatory genes (COX-2 and IL-6), and cellular senescence biomarker p21, possibly by suppressing activator protein-1 signaling., Conclusions: This study demonstrates the protective effects of GrDENs against skin damage caused by UV and oxidative stress, providing new insights into beneficial uses of ginseng . In particular, our results suggest GrDENs as a potential active ingredient in cosmeceuticals to promote skin health., (© 2024 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

In cancer treatment, multi-target approach has paid attention to a reasonable strategy for the potential agents. We investigated whether (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) could exert an anticancer effect by dual-regulating VEGFR2 and PPARγ. MMPP showed modulating effects in TNBC type (MDA-MB-231 and MDA-MB-468) and luminal A type (MCF7) breast cancer cell lines. MMPP enhanced PPARγ transcriptional activity and inhibited VEGFR2 phosphorylation. MMPP-induced signaling by VEGFR2 and PPARγ ultimately triggered the downregulation of AKT activity. MMPP exhibited anticancer effects, as evidenced by growth inhibition, inducement of apoptosis, and suppression of migration and invasion. At the molecular level, MMPP activated pro-apoptotic proteins (caspase3, caspase8, caspase9, and bax), while inhibiting the anti-apoptotic proteins (bcl2). Additionally, MMPP inhibited the mRNA expressions of EMT-promoting transcription factors. Therefore, our findings showed molecular mechanisms of MMPP by regulating VEGFR2 and PPARγ, and suggested that MMPP has potential to treat breast cancer.

Background: Poor functional status relating to heart failure (HF) negatively affects health-related quality of life (HRQOL). Patients with HF, especially those with New York Heart Association (NYHA) Class III or IV HF, often exhibit poor HRQOL because of physical limitations and HF-related symptoms. Although sense of coherence (SOC) has been reported to be a determinant of HRQOL, its role as a mediator between functional status and HRQOL remains unclear, and few studies have explored the prevalence of HF in patients in NYHA Classes I and II., Purpose: This study was designed to investigate SOC as a mediator between different functional status classes and HRQOL in patients with HF., Methods: A cross-sectional study was conducted on patients with HF recruited from a hospital in northern Taiwan from April 2020 to September 2020. The Minnesota Living with Heart Failure Questionnaire and a questionnaire on sociodemographic characteristics; functional classification in terms of NYHA Classes I, II, and III; and SOC were administered. The PROCESS v3.5 (by Andrew F. Hayes) macro was applied to analyze the effects, and Model 4 was used to examine the mediating role of SOC on the relationship between NYHA functional class and HRQOL., Results: Of the 295 participants, SOC was found to mediate the effects of functional status on HRQOL more significantly in patients in Class II than those in Class III but not more significantly in patients in Class I than those in Class III. A weaker mediating effect of SOC was noted on the relationship between functional status and HRQOL in patients with HF in NYHA Class II than those in Class III., Conclusions: In patients with HF, poor functional status often reduces HRQOL significantly. SOC mediates the relationship between functional status and HRQOL more significantly in those in NYHA Class II than those in Class III. Nursing staff should work to increase patients' SOC by strengthening their coping capacity and improving their functional status to improve their HRQOL., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Introduction: Polypharmacy and potentially inappropriate medications (PIM) are common among older adults. To guide appropriate prescribing, healthcare professionals often rely on explicit criteria to identify and deprescribe inappropriate medications, or to start medications due to prescribing omission. However, most explicit PIM criteria were developed with inadequate guidance from quality metrics or integrating real-world data, which are rich and valuable data source., Aim: To develop a list of medications to facilitate appropriate prescribing among older adults., Methods: A preliminary list of PIM and potential prescribing omission (PPO) were generated from systematic review, supplemented with local pharmacovigilance data of adverse reaction incidents among older people. Twenty-one experts from nine specialties participated in two Delphi to determine the list of PIM and PPO in February and March 2023. Items that did not reach consensus after the second Delphi round were adjudicated by six geriatricians., Results: The preliminary list included 406 potential candidates, categorised into three sections: PIM independent of diseases, disease dependent PIM and omitted drugs that could be restarted. At the end of Delphi, 92 items were decided as PIM, including medication classes, such as antacids, laxatives, antithrombotics, antihypertensives, hormones, analgesics, antipsychotics, antidepressants, and antihistamines. Forty-two disease-specific PIM criteria were included, covering circulatory system, nervous system, gastrointestinal system, genitourinary system, and respiratory system. Consensus to start potentially omitted treatment was achieved in 35 statements across nine domains., Conclusions: The newly developed PIM criteria can serve as a useful tool to guide clinicians and pharmacists in identifying PIMs and PPOs during medication review and facilitating informed decision-making for appropriate prescribing., (© 2023. Dr. Zaheer-Ud-Din Babar and Auckland UniServices Ltd.)

The purpose of this study was to examine the factors that predict life satisfaction in a large representative sample of Koreans by analyzing data from the Gallup World Poll. The primary objective was to identify important predictors and suggest strategies to improve quality of life in Korea. The study used available Korean data from 2006 to 2017, which included 14,101 participants (mean age = 46.42). Predictors included demographic and psychological variables, with the Cantril Ladder of Life Scale serving as the outcome variable. The results show a decline in life satisfaction with advancing age, and that the relationship between life satisfaction and age varied by gender. Among the predictors examined, satisfaction with the standard of living and household income emerged as the most influential factors in determining life evaluation; other strong predictors included positive affect and negative affect, social support, gender, and education level. These results imply that, to increase life satisfaction, it is imperative to provide job opportunities and social services specifically targeted to individuals in low-income groups. In addition, it is crucial to implement tailored psychosocial interventions that address the unique developmental tasks and psychological challenges experienced by individuals according to their gender and life cycle stage.