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Chun-Lin Kuo,1 Shu-Man Hsieh Li,*,2 Shu-Yi Liang,*,2 Shu-Ting Liu,2 Li-Chun Huang,2 Wei-Ming Wang,3 Li-Chen Yen,2,4 Shih-Ming Huang21Department of Orthopaedic Surgery, Tri-Service General Hospital, National Defense Medical Center, Taiwan, Republic of China; 2Department of Biochemistry, National Defense Medical Center, Taiwan, Republic of China; 3Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taiwan, Republic of China; 4Department of Microbiology and Immunology, National Defense Medical Center, Taiwan, Republic of China*These authors contributed equally to this workBackground: Differentiated embryo chondrocyte 1 (DEC1) is a helix-loop-helix transcription factor that directly binds to the class B E-box in target genes. DEC1 exerts both pro-survival and pro-apoptotic effects in a cell- and tissue-dependent manner. Its actions play role the progression of cancer remains unclear.Methods: We first examined the functional roles of DEC1 using the transient promoter reporter assay. Then, the knockdown of DEC1 expression was performed with the short hairpin RNA strategy in HeLa and A2058 cancer cell lines to check the cell cycle and mitochondrial function profile using the flow cytometry and Seahorse assays. We later clarified the role of DEC1 in the tumorigenesis using the colony formation, anchorage-independent growth assay, and cellular proliferation analysis.Results: In the present study, we tested two guanide-containing drugs, metformin and phenformin, and found that both exhibit cytotoxicity against HeLa cervical carcinoma and A2058 melanoma cells. This effect was mediated, at least in part, through activation of the AMPK pathway; degradation of important cellular proteins, such as DEC1 and p53; and suppression of mitochondrial function, colony formation, and anchorage-independent cell proliferation. Our results further suggest that the cytotoxicity of metformin and phenformin reflect the impact of the repressive actions of DEC1 on gene expression, including DEC1 itself. This in turn suppresses both anchorage-independent growth and cell proliferation.Conclusion: These findings provide several lines of evidence suggesting that DEC1 activity contributes to tumorigenicity and that the antitumor properties of biguanides reflect their ability to inhibit DEC1 functions.Keywords: differentiated embryo chondrocyte 1, p53, metformin, phenformin, tumorigenesis

Chih-Lan Kuo1, Sui-Foon Lo1,2, Chun-Lin Liu3, Chia-Hui Chou4, Li-Wei Chou1,2,5¹Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; ²School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 3Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan; 4Department of Infectious disease, China Medical University Hospital, Taichung, Taiwan; 5Department of Physical Therapy, China Medical University, Taichung, TaiwanAbstract: There are few reports in the literature of tuberculous brain abscess. Tuberculous brain abscess usually occurs in an immunocompromised host. Almost all previously documented cases have involved acquired immune deficiency syndrome. We encountered a 53-year-old right-handed immunocompetent male who was initially suspected of having a cerebrovascular accident due to acute-onset right hemiparesis and paresthesia. A tentative diagnosis of brain tumor versus brain abscess was made on imaging studies. The patient was finally diagnosed with a tuberculous brain abscess based upon deterioration on imaging and a positive tuberculosis culture. The tuberculous brain abscess was located in the left parietal lobe, which resulted in Gerstmann's syndrome and right-sided apraxia. Stereotactic surgery was performed. He was also given antituberculosis chemotherapy and comprehensive rehabilitation. Considerable improvement was noted after rehabilitation. The patient even returned to a normal life and work. Our case demonstrates that an aggressive intensive inpatient rehabilitation program combined with stereotactic surgery and effective antituberculosis therapy play an important role in improving the outcome for patients with tuberculous brain abscess, Gerstmann's syndrome, and right-sided apraxia.Keywords: tuberculous brain abscess, Gerstmann's syndrome, rehabilitation

LiteBIRD, the Lite (Light) satellite for the study of B-mode polarization and Inflation from cosmic background Radiation Detection, is a space mission for primordial cosmology and fundamental physics. The Japan Aerospace Exploration Agency (JAXA) selected LiteBIRD in May 2019 as a strategic large-class (L-class) mission, with an expected launch in the late 2020s using JAXA’s H3 rocket. LiteBIRD is planned to orbit the Sun–Earth Lagrangian point L2, where it will map the cosmic microwave background polarization over the entire sky for three years, with three telescopes in 15 frequency bands between 34 and 448 GHz, to achieve an unprecedented total sensitivity of 2.2 μK-arcmin, with a typical angular resolution of 0.5◦ at 100 GHz. The primary scientific objective of LiteBIRD is to search for the signal from cosmic inflation, either making a discovery or ruling out well-motivated inflationary models. The measurements of LiteBIRD will also provide us with insight into the quantum nature of gravity and other new physics beyond the standard models of particle physics and cosmology. We provide an overview of the LiteBIRD project, including scientific objectives, mission and system requirements, operation concept, spacecraft and payload module design, expected scientific outcomes, potential design extensions, and synergies with other projects.

Inflation is the leading theory of the first instant of the universe. Inflation, which postulates that the universe underwent a period of rapid expansion an instant after its birth, provides convincing explanation for cosmological observations. Recent advancements in detector technology have opened opportunities to explore primordial gravitational waves generated by the inflation through “B-mode” (divergent-free) polarization pattern embedded in the cosmic microwave background anisotropies. If detected, these signals would provide strong evidence for inflation, point to the correct model for inflation, and open a window to physics at ultra-high energies. LiteBIRD is a satellite mission with a goal of detecting degree-and-larger-angular-scale B-mode polarization. LiteBIRD will observe at the second Lagrange point with a 400 mm diameter telescope and 2622 detectors. It will survey the entire sky with 15 frequency bands from 40 to 400 GHz to measure and subtract foregrounds. The US LiteBIRD team is proposing to deliver sub-Kelvin instruments that include detectors and readout electronics. A lenslet-coupled sinuous antenna array will cover low-frequency bands (40–235 GHz) with four frequency arrangements of trichroic pixels. An orthomode-transducer-coupled corrugated horn array will cover high-frequency bands (280–402 GHz) with three types of single frequency detectors. The detectors will be made with transition edge sensor (TES) bolometers cooled to a 100 milli-Kelvin base temperature by an adiabatic demagnetization refrigerator. The TES bolometers will be read out using digital frequency multiplexing with Superconducting QUantum Interference Device (SQUID) amplifiers. Up to 78 bolometers will be multiplexed with a single SQUID amplifier. We report on the sub-Kelvin instrument design and ongoing developments for the LiteBIRD mission.

The high-frequency telescope for LiteBIRD is designed with refractive and reflective optics. In order to improve sensitivity, this paper suggests the new optical configurations of the HFT which have approximately 7 times larger focal planes than that of the original design. The sensitivities of both the designs are compared, and the requirement of anti-reflection (AR) coating on the lens for the refractive option is derived. We also present the simulation result of a sub-wavelength AR structure on both surfaces of silicon, which shows a band-averaged reflection of 1.1–3.2% at 101–448 GHz.

In this paper, we describe the optimization of transition-edge-sensor (TES) detector arrays for the third-generation camera for the South Pole Telescope. The camera, which contains ~ 16 000 detectors, will make high-angular-resolution maps of the temperature and polarization of the cosmic microwave background. Our key results are scatter in the transition temperature of Ti/Au TESs is reduced by fabricating the TESs on a thin Ti(5 nm)/Au(5 nm) buffer layer and the thermal conductivity of the legs that support our detector islands is dominated by the SiOx dielectric in the microstrip transmission lines that run along the legs.

LiteBIRD is a proposed CMB polarization satellite project to probe the inflationary B-mode signal. The satellite is designed to measure the tensor-to-scalar ratio with a 68 % confidence level uncertainty of σr< 10 - 3, including statistical, instrumental systematic, and foreground uncertainties. LiteBIRD will observe the full sky from the second Lagrange point for 3 years. We have a focal plane layout for observing frequency coverage that spans 40–402 GHz to characterize the galactic foregrounds. We have two detector candidates, transition-edge sensor bolometers and microwave kinetic inductance detectors. In both cases, a telecentric focal plane consists of approximately 2 × 10 3 superconducting detectors. We will present the mission overview of LiteBIRD, the project status, and the TES focal plane layout.

Fluctuations in the intensity and polarization of the cosmic microwave background (CMB) and the large-scale distribution of matter in the universe each contain clues about the nature of the earliest moments of time. The next generation of CMB and large-scale structure (LSS) experiments are poised to test the leading paradigm for these earliest moments-the theory of cosmic inflation-and to detect the imprints of the inflationary epoch, thereby dramatically increasing our understanding of fundamental physics and the early universe. A future CMB experiment with sufficient angular resolution and frequency coverage that surveys at least 1% of the sky to a depth of 1 uK-arcmin can deliver a constraint on the tensor-to-scalar ratio that will either result in a 5σ measurement of the energy scale of inflation or rule out all large-field inflation models, even in the presence of foregrounds and the gravitational lensing B-mode signal. LSS experiments, particularly spectroscopic surveys such as the Dark Energy Spectroscopic Instrument, will complement the CMB effort by improving current constraints on running of the spectral index by up to a factor of four, improving constraints on curvature by a factor of ten, and providing non-Gaussianity constraints that are competitive with the current CMB bounds.

This is a report on the status and prospects of the quantification of neutrino properties through the cosmological neutrino background for the Cosmic Frontier of the Division of Particles and Fields Community Summer Study long-term planning exercise. Experiments planned and underway are prepared to study the cosmological neutrino background in detail via its influence on distance-redshift relations and the growth of structure. The program for the next decade described in this document, including upcoming spectroscopic galaxy surveys eBOSS and DESI and a new Stage-IV CMB polarization experiment CMB-S4, will achieve σ(σmν) = 16 meV and σ(Neff) = 0.020. Such a mass measurement will produce a high significance detection of non-zero σmν, whose lower bound derived from atmospheric and solar neutrino oscillation data is about 58 meV. If neutrinos have a minimal normal mass hierarchy, this measurement will definitively rule out the inverted neutrino mass hierarchy, shedding light on one of the most puzzling aspects of the Standard Model of particle physics - the origin of mass. This precise a measurement of Neff will allow for high sensitivity to any light and dark degrees of freedom produced in the big bang and a precision test of the standard cosmological model prediction that Neff = 3.046.

Antrodia cinnamomea (named as Niu-chang-chih), a well-known Taiwanese folk medicinal mushroom, has a spectrum of biological activities, especially with anti-tumor property. This study was carried out for the first time to examine the potential role and the underlying mechanisms of A. cinnamomea in the differentiation of human leukemia HL60 cells. We found that the methanol extract of liquid cultured mycelia of A. cinnamomea (MEMAC) inhibited proliferation and induced G1-phase cell cycle arrest in HL60 cells. MEMAC could induce differentiation of HL60 cells into the monocytic lineage, as evaluated by the morphological change, nitroblue tetrazolium reduction assay, non-specific esterase assay, and expression of CD14 and CD11b surface antigens. In addition, MEMAC activated the extracellular signal-regulated kinase (ERK) pathway and increased CCAAT/enhancer-binding protein [beta] (C/EBP[beta]) expression. Reverse transcriptase polymerase chain reaction analysis showed that MEMAC upregulated the expression of C/EBP[beta] and CD14 mRNA in HL60 cells. DNA affinity precipitation assay and chromatin immunoprecipitation analyses indicated that MEMAC enhanced the direct binding of C/EBP[beta] to its response element located at upstream of the CD14 promoter. Furthermore, inhibiting ERK pathway activation with PD98059 markedly blocked MEMAC-induced HL60 monocytic differentiation. Consistently, the MEMAC-mediated upregulation of C/EBP[beta] and CD14 was also suppressed by PD98059. These findings demonstrate that MEMAC-induced HL60 cell monocytic differentiation is via the activating ERK signaling pathway, and downstream upregulating the transcription factor C/EBP[beta] and differentiation marker CD14 gene, suggesting that MEMAC might be a potential differentiation-inducing agent for treatment of leukemia. [ABSTRACT FROM AUTHOR]

BACKGROUND: : Journaling has been incorporated into many nursing courses as an active reflective teaching strategy that can facilitate the learning process, personal growth, and professional development of students. There is limited research support of journaling as an appropriate tool to promote reflection for the purpose of learning caring in nursing education. PURPOSE: : The aim of this study was to explore the experiences and perceptions of student nurses and instructors who use clinical caring journaling (CCJ) in their clinical practicum. METHODS: : Researchers used a descriptive qualitative research design. The study population was 880 senior student nurses and 90 clinical instructors from a nursing program at a university in Taiwan who used CCJ. After completion of 1 year of clinical practicum, 16 students and 7 instructors participated voluntarily in focus group interviews. Researchers used content analysis to sort interview data into themes. RESULTS: : Six themes were categorized that encapsulated student and instructor experiences and perceptions regarding using CCJ in their clinical practicum. These themes were guiding caring behavior toward patients, enabling students' reflective caring abilities, building up students' self-confidence, increasing interaction between students and instructors, enhancing students' self-development, and overcoming writing difficulty. CONCLUSIONS/IMPLICATIONS FOR PRACTICE:: Research findings may serve as a reference for nursing educators to use CCJ strategy in student nurses' clinical practicum. [ABSTRACT FROM AUTHOR]

Summary Objective: A large number of structurally and functionally diverse compounds act as substrates or modulators of p-glycoprotein (p-gp). Some of them possess multiple drug resistance (MDR)-reversing activity, but only a small number of them have entered clinical study. In order to uncover the factors which exert a significant impact on the interaction between substrates/modulators and p-gp, we have performed structure-activity relationship (SAR) analyses, including molecular modelling, two-dimensional (2D) and three-dimensional (3D) parameter-frame-setting analysis, quantitative structure activity relationship (QSAR) analysis among substrates/modulators, as well as clinically promising MDR-reversing agents. Methods: The physicochemical parameters C log P , CMR and all regression equations were derived by using C log P version 4·0 and the latest CQSAR software, respectively. Molecular modelling and all other parameter calculations were performed by using HyperChem version 5·0 program, after geometry optimization and energy minimization using the AM1 semiempirical method. Results: SAR analyses indicate that MDR reversal activity is correlated with the lipophilicity (C log P ), molecular weight (log M w ), longest chain (N lc ) of the molecule and the energy of the highest occupied orbital (E homo ). In addition, the presence of a basic tertiary nitrogen atom in the structure is also an important contributor to p-gp inhibitory activity. Some separation in space is achieved for different subsets of p-gp substrates and inhibitors using N lc , C log P and E homo as three independent parameters in the 3D-parameter-frame setting. Conclusion: A highly effective p-gp modulator candidate should possess a log P value of 2·92 or higher, 18-atom-long or longer molecular axis, and a high E homo value, as well as at least one tertiary basic nitrogen atom. The results... [ABSTRACT FROM AUTHOR]

Objectives: Findings regarding the effects of vitamin D supplementation on diabetes risk are inconclusive. Because inflammation and vitamin D levels are interconnected, we hypothesized that higher inflammation levels moderate the effects of vitamin D deficiency on diabetes risk., Design, Setting, Participants, and Measurements: UK Biobank participants without pre-existing diabetes at baseline were included (N = 336,500). We first linked vitamin D and C-reactive protein (CRP; inflammation measure) levels with incident diabetes during a mean follow-up of 13.5 years (SD = 1.9). Then, we investigated the moderation effect of CRP on the associations between vitamin D deficiency (<10 ng/mL) and incident diabetes and performed subgroup analyses according to age (<60 vs. ≥60 years) and frailty status (frail; pre-frail; non-frail). Multivariate analyses were conducted using restricted cubic spline Cox proportional hazards regression models., Results: Lower vitamin D and higher CRP levels were significantly associated with an increased risk of diabetes during follow-up. There was a significant interaction between vitamin D deficiency and CRP on incident diabetes (p < 0.001). In participants with higher levels of CRP, the hazard ratio of developing diabetes comparing participants who had vitamin D deficiency to those who did not was lower than that in participants with lower levels of CRP. The moderation effect of CRP was similar between younger and older adults but was stronger in frail or pre-frail older adults than in non-frail older adults., Conclusion: Our findings indicate that the effect of vitamin D deficiency on incident diabetes may be affected by inflammation. This finding may explain the inconsistent results from vitamin D supplementation trials. Vitamin D supplementation without considering the potential impact of inflammation might prove unsatisfactory., Competing Interests: Declaration of competing interest We have no conflicting interests to disclose., (Published by Elsevier Masson SAS.)

Lower urinary tract dysfunction (LUTD) increases with aging. Ensuing symptoms including incontinence greatly impact quality of life, isolation, depression, and nursing home admission. The aging bladder is hypothesized to be central to this decline, however, it remains difficult to pinpoint a singular strong driver of aging-related bladder dysfunction. Many molecular and cellular changes occur with aging, contributing to decreased resilience to internal and external stressors, affecting urinary control and exacerbating LUTD. In this study, we examined whether cellular senescence, a cell fate involved in the etiology of most aging diseases, contributes to LUTD. We found that umbrella cells (UCs), luminal barrier uroepithelial cells in the bladder, show senescence features over the mouse lifespan. These polyploid UCs exhibit high cyclin D1 staining, previously reported to mediate tetraploidy-induced senescence in vitro. These senescent UCs were not eliminated by the senolytic combination of Dasatinib and Quercetin. We also tested the effect of a high-fat diet (HFD) and senescent cell transplantation on bladder function and showed that both models induce cystometric changes similar to natural aging in mice, with no effect of senolytics on HFD-induced changes. These findings illustrate the heterogeneity of cellular senescence in varied tissues, while also providing potential insights into the origin of urothelial cancer. We conclude that senescence of bladder uroepithelial cells plays a role in normal physiology, namely in their role as barrier cells, helping promote uroepithelial integrity and impermeability and maintaining the urine-blood barrier., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Statement of Problem: Studies examining mid-term treatment outcomes of implant placement with bone augmentation in patients with compromised bone health are lacking., Purpose: The purpose of this prospective, nonrandomized cohort study was to evaluate the cone bean computed tomography (CBCT) outcomes of implant placement with bone augmentation in postmenopausal women., Material and Methods: For this best practice, standard of care study, 78 participants received 1 test implant along with 1 or a combination of 3 bone augmentation procedures: particulate graft, expansion, or block graft. Participants were categorized as healthy (n=49) or bone compromised (n=29). Using CBCT scans made preoperatively, immediately postoperatively, and 2 years postoperatively, the augmented alveolar ridge widths were measured in a buccolingual (BL) dimension 2 mm and 6 mm apical to the coronal aspect of the implant's rough surface. Additionally, peri-implant bone height was measured on the mesial and distal implant surfaces at the mid-alveolar aspect of the ridge using a coronal panoramic view., Results: Both study groups exhibited an increase in horizontal BL measurements at the 2-mm and 6-mm landmarks from preoperative to immediate postoperative time points and a minimal decrease from intermediate postoperative to 2 years postoperative. The mean proximal height decreased over time in healthy participants but did not show a significant change in participants with compromised bone. The linear mixed effects model results revealed that the mean difference between groups significantly decreased over time at the 2-mm landmark (P<.05); however, no significant group-time interactions were found for the BL width at the 6-mm landmark and proximal height measurements (P=.627)., Conclusions: Mid-term CBCT measurements showed significant bone augmentation immediately after surgery and 2 years after surgery and stable proximal bone adjacent to implants in postmenopausal women diagnosed with compromised bone health., (Copyright © 2024 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Solanum torvum Sw. (ST) is used to clear heat toxins, promote blood circulation, and alleviate blood stasis. Therefore, this plant has traditionally been used as an ethnomedicine for common cold, chronic gastritis, and tumors., Aim of the Study: This study aimed to elucidate the mechanism by which ST induces ferroptosis in hepatocellular carcinoma (HCC), the combination effect with lenvatinib, and the impact on lenvatinib-resistant cells., Materials and Methods: Cell viability assays were performed using different hepatoma cell lines treated with ST. Lipid peroxidation and iron assays were performed using flow cytometry. Molecules involved in the ferroptosis pathway were detected by Western blotting. Finally, a lenvatinib-resistant cell line was established to evaluate the antiproliferative effects of ST., Results: ST ethanol extract inhibited the growth of various hepatoma cell lines. A significant reduction in glutathione peroxidase 4 (GPX4) expression was observed following ST treatment, which was accompanied by increased lipid peroxidation and Fe 2+ accumulation. ST induced ferroptosis mainly through heme oxygenase-1 (HO-1) expression. HO-1 knockdown reduced ST-induced lipid peroxidation and reversed GPX4 suppression. Acyl-CoA synthetase long-chain family member 4 (ACSL4) also participated in ST-induced ferroptosis. ST and lenvatinib combination showed an additive effect, and ST retained its potential anti-HCC efficacy in a lenvatinib-resistant cell line., Conclusion: This study demonstrated that the ethanol extract of ST inhibits hepatoma cell growth by inducing ferroptosis. ST displayed an additive effect with lenvatinib in Hep 3B cells and showed remarkable anti-HCC activity in lenvatinib-resistant Hep 3B cells. Collectively, the study shows that ST might have the potential to reduce lenvatinib use in clinical practice and salvage cases of lenvatinib resistance., 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 B.V. All rights reserved.)

Background: Gastrointestinal dysfunction frequently occurs following traumatic brain injury (TBI) and significantly increases posttraumatic complications. TBI can lead to alterations in gut microbiota. The neuroprotective effects of hyperbaric oxygen (HBO) have not been well recognized after TBI. The study''s aim was to investigate the impact of HBO on TBI-induced dysbiosis in the gut and the pathological changes in the brain following TBI., Methods: Anesthetized male Sprague-Dawley rats were randomly assigned to three groups: sham surgery plus normobaric air (21% oxygen at 1 atmospheres absolute), TBI (2.0 atm) plus normobaric air, and TBI (2.0 atm) plus HBO (100% oxygen at 2.0 atmospheres absolute) for 60 min immediately after TBI, 24 h later, and 48 h later. The brain injury volume, tumor necrosis factor-α expression in microglia and astrocytes, and neuronal apoptosis in the brain were subsequently determined. The V3-V4 regions of 16S ribosomal rRNA in the fecal samples were sequenced, and alterations in the gut microbiome were statistically analyzed. All parameters were evaluated on the 3rd day after TBI., Results: Our results demonstrated that HBO improved TBI-induced neuroinflammation, brain injury volume, and neuronal apoptosis. HBO appeared to increase the abundance of aerobic bacteria while inhibiting anaerobic bacteria. Intriguingly, HBO reversed the TBI-mediated decrease in Prevotella copri and Deinococcus spp., both of which were negatively correlated with neuroinflammation and brain injury volume. TBI increased the abundance of these gut bacteria in relation to NOD-lik0065 receptor signaling and the proteasome pathway, which also exhibited a positive correlation trend with neuro inflammation and apoptosis. The abundance of Prevotella copri was negatively correlated with NOD-like receptor signaling and the Proteasome pathway., Conclusions: Our study demonstrated how the neuroprotective effects of HBO after acute TBI might act through reshaping the TBI-induced gut dysbiosis and reversing the TBI-mediated decrease of Prevotella copri., Competing Interests: Conflicts of interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Ethical Approval/Informed Consent: Tthis study obtained ethics approval (no. 110122310) from the Chi Mei Medical Centre Animal Care and Use Committee and conformed to National Institutes of Health guidelines., (© 2024. The Author(s).)

Phenethyl isothiocyanate (PEITC), a natural product, exists in biological activities, including anticancer activity in many human cancer cells. No information shows that PEITC affects DNA damage in human retinoblastoma (RB) cells in vitro. In this study, the aim of experiments was to determine whether PEITC decreased total viable cell number or not by inducing protein expressions involved in DNA damage and repair in Y79 RB cells in vitro. Total cell viability was measured by PI exclusion assay, and PEITC reduced the total Y79 viable cell numbers in a dose-dependent manner. DNA condensation and DNA impairment were conducted by DAPI staining and comet assays, respectively, in Y79 cells. The findings show that PEITC induced DNA condensation dose-dependently based on the brighter fluorescence of cell nuclei stained by DAPI staining. PEITC-induced DNA damage showed a more extended DNA migration smears than that of the control, which was performed by a comet assay. Western blotting was performed to measure the protein expressions involved in DNA damage and repair, which showed that PEITC at 2.5-10 μM increased NRF2, HO-1, SOD (Mn), and catalase; however, it decreased SOD (Cu/Zn) except 10 μM PEITC treatment, and decreased glutathione, which were associated with oxidative stress. Furthermore, PEITC increased DNA-PK, MDC1, H 2 A.X pSer139 , ATM pSer1981 , p53, p53 pSer15 , PARP, HSP70, and HSP90, but decreased TOPIIα, TOPIIβ, and MDM2 pSer166 that were associated with DNA damage and repair mechanism in Y79 cells. The examination from confocal laser microscopy shows that PEITC increased H 2 A.X pSer139 and p53 pSer15 , and decreased glutathione and TOPIIα in Y79 cells. In conclusion, the cytotoxic effects of PEITC on reducing the number of viable cells may be due to the induction of DNA damage and the alteration of DNA repair proteins in Y79 cells in vitro., (© 2024 Wiley Periodicals LLC.)

Rheumatoid arthritis (RA) is an autoimmune disease that causes persistent inflammation involving the joints, cartilage, and synovium. In individuals with RA, alterations in the composition of intestinal bacteria suggest the vital role of gut microbiota in immune dysfunction. Multiple therapies commonly used to treat RA can also alter the diversity of gut microbiota, further suggesting the modulation of gut microbiota as a prevention or treatment for RA. Therefore, a better understanding of the changes in the gut microbiota that accompany RA should facilitate the development of novel therapeutic approaches. In this study, B. coagulans BACO-17 not only significantly reduced paw swelling, arthritis scores, and hind paw and forepaw thicknesses but also protected articular cartilage and the synovium against RA degeneration, with a corresponding downregulation of TNF-α expression. The inhibition or even reversing of RA progression highlights B. coagulans BACO-17 as a novel therapeutic for RA worth investigating., 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 B.V. All rights reserved.)

Background: Biomarkers for sarcopenia are lacking. We examined the diagnostic power of serum creatinine to cystatin C (Cr:Cyc) ratio for identifying low MRI-muscle volume and low grip strength in a large observational study of UK Biobank older adults., Methods: Serum creatinine and cystatin C were measured via immunoassays (Beckman Coulter AU5800 and Siemens Advia 1800, respectively) and grip strength by hydraulic hand dynamometer at baseline visit (2008-2010). MRI-thigh fat-free muscle volume (FFMV) and DXA-derived appendicular lean mass were measured at imaging visit (2014-2018). Extreme outliers were removed, and covariates (demographic, lifestyle, and clinical factors, as well as time elapsed between baseline-imaging visit) were adjusted for in statistical models., Results: 12,873 older adults (mean age: 63.5 ± 2.7 years, 44.2% women) were included for FFMV and ALM/BMI; 149,707 older adults (mean age: 64.0 ± 2.9 years, 50.5% women) for grip strength. Despite significant associations (p<0.05), in fully-adjusted models, Cr:Cyc showed poor to acceptable diagnostic power for identifying low FFMV when using cutpoints of 20th percentile (AUC: 0.577 men; 0.622 women) and T scores of -2 (AUC: 0.596 men; 0.659 women) and -2.5 (AUC: 0.609 men; 0.722 women). In fully-adjusted model, Cr:Cyc showed poor diagnostic power (AUCs: <0.70) for identifying low ALM/BMI or low grip strength irrespective of the cutpoint used., Conclusions: Cr:Cyc may not be a suitable biomarker for identifying low muscle volume or low strength in older adults. This finding, drawn from a large sample size and the use of advanced medical imaging, marks an important contribution to the sarcopenia field., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

We developed a novel adeno-associated virus 5 gene therapy (AAV5-GLA) expressing human alpha-galactosidase A (GLA) under the control of a novel, small and strong, liver-restricted promoter. We assessed the preclinical potential of AAV5-GLA for treating Fabry disease, an X-linked hereditary metabolic disorder resulting from mutations in the gene encoding GLA that lead to accumulation of the substrates globotriaosylceramide and globotriaosylsphingosine, causing heart, kidney, and central nervous system dysfunction. Effects of intravenously administered AAV5-GLA were evaluated in (1) GLA-knockout mice aged 7-8 weeks (early in disease) and 20 weeks (nociception phenotype manifestation) and (2) cynomolgus macaques during an 8-week period. In both species, AAV5-GLA was observed as safe, generated detectable vector DNA and mRNA levels in liver, and produced stable enzyme activity in liver and plasma. In mice, dose-dependent transgene enzyme activity, cross-correction (substrate reduction) in kidney and heart, and improved nociception lasted over 6 months. Moreover, after delayed administration when animals displayed the nociception phenotype, target organ enzyme activity was present, and accumulated substrates were reduced. Given the strong, durable expression of active GLA with this promoter and favorable profile of adeno-associated virus 5-based gene therapy in humans, AAV5-GLA warrants further investigation in clinical trials for Fabry disease., Competing Interests: J.M.P.L., G.B., E.A.S., L.P., and L.K.S. are employees and shareholders of uniQure biopharma B.V. N.E. and M.M.E. were employees and shareholders of uniQure biopharma B.V. at the time these studies were conducted. P.S.M.-M. is an employee of VectorY Therapeutics B.V. and was an employee of uniQure biopharma B.V. at the time these studies were conducted. Y.P.L. is listed as an inventor on PCT/EP2019/081743 and is an employee and shareholder of uniQure biopharma B.V., (© 2024 uniQure Biopharma B.V.)

Objective: This study compared the achieved tooth movement to that predicted in the preliminary simulated digital treatment plan between adults and teenagers., Materials and Methods: Records of 60 patients (30 adults; mean age: 36.6 ± 11.36 years, and 30 teenagers; mean age: 16.23 ± 2.25 years) were randomly selected. Initial and predicted models were obtained from the initial simulated treatment plan. The first model of the refinement scan was labeled as achieved. SlicerCMF software (version 3.1; https://www.slicer.org ) was used to superimpose the achieved and predicted digital models over the initial ones with regional superimposition on relatively stable first molars. 600 teeth were measured in each group for horizontal, vertical, angular movements, and transverse dimensions. Accuracy was defined as the achieved amount of movement minus predicted and was calculated for each individual and compared between teens and adults., Results: The mandibular inter-canine width accuracy was statistically significant between groups (p = 0.050). Significant under-correction in horizontal movements was noted for mandibular first premolars in teenagers compared to adults (p = 0.037). There was considerable over-correction in horizontal movements for mandibular central and lateral incisors between groups (p < 0.05). No significant difference was observed between groups in the vertical plane. Rotations were underachieved for maxillary first premolars, more in adults than teenagers (p = 0.017)., Conclusion: The accuracy of achieved versus predicted tooth movement between adults and teenagers was significant for the inter-canine width. Mandibular central and lateral incisors showed significantly greater over-correction in adults in the horizontal plane. The accuracy of rotations and vertical movements was comparable., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Effective interprofessional collaboration practice (IPCP) promotes healthcare outcomes but is often hindered by poor communication. Traditional teaching methods with limited interdisciplinary interactions may not effectively foster IPCP behaviors. This study evaluated the effectiveness of nurse-led World Cafe (NWC) approach in promoting IPCP behaviors and learning engagement. Seventy-six healthcare professionals (38 in each group) participated in this quasi-experimental study. Data were collected before, one-week, and four-week post-intervention, using Lee's (2016) Interprofessional Collaborative Practice Behavior Inventory (IPCPBI) and Ciou's (2020) Learning Engagement Scale. Five medical technologists in the control group were excluded from data analysis to ensure group equivalence. Before the intervention, there were no significant differences in IPCPBI between groups. One week post-intervention, the experimental group scored higher in IPCPBI, yet lacked statistical significance ( p  > .05). Four weeks post-intervention, the experimental group significantly improved in IPCPBI ( p  < .05). While no statistically significance was found in learning engagement between groups, the experimental group scored significantly higher in the active engagement sub-domain ( p  < .05). The NWC approach boosted IPCP behaviors and learning engagement, fostering a collaborative learning environment that improves outcomes through interdisciplinary interactions. Healthcare settings could benefit from adopting the NWC approach to enhance clinicians' IPCP competency.

Introduction: The objective of this study was to evaluate the short-term and long-term hard-tissue changes with miniscrew-assisted rapid palatal expansion (MARPE) and rapid palatal expansion (RPE) compared with a matched control group with voxel-based superimposition using 3-dimensional cone-beam computed tomography (CBCT) scans., Methods: A total of 180 CBCT scans were analyzed for 60 patients with a mean age of 13.9 years at 3 time points: pretreatment (T1), postexpansion (T2), and posttreatment (T3). Patients were divided into 3 groups: MARPE, RPE, and controls. Voxel-based superimposition was performed for CBCTs from T1 to T2 and T1 to T3 using the anterior cranial base as a reference. The hard-tissue surfaces were extracted after the superimposition procedure. Nine landmarks were analyzed: nasion, A-point, pogonion, left and right alar bases, zygoma, and gonion. Within-group changes were analyzed using linear mixed-effects models, including a random intercept per subject and the mixed effect of time (T1, T2, or T3) with test P values adjusted for multiple testing using Tukey's method. Between-group changes were analyzed using linear mixed-effects models, including a random intercept per subject and the mixed effects of time, group, and group × time interaction with P values adjusted for multiple testing using the Benjamin-Hochberg false discovery rate method., Results: In the short term, both MARPE and RPE led to a significant downward movement of the right gonion and lateral movement of the right alar base compared with controls at T2 (P <0.05). In addition, MARPE led to a significant downward movement of pogonion and left gonion. RPE led to a significant downward movement of the A-point and lateral movement of the left alar base compared with controls at T2 (P <0.05). However, in the long-term, no changes were observed between the groups at T3., Conclusions: There were significant differences in pogonion, alar base, and gonion between MARPE, RPE, and control groups in the short term. However, all the hard-tissue changes were transient, as there were no differences between the 3 groups in the long term., (Copyright © 2024 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Abstract: This report presents a case of suspected Parkinson disease in a 76-year-old woman with a history of slurred speech, general weakness, unstable gait, and bradykinesia for months. A 99m Tc-TRODAT-1 SPECT scan revealed a symmetrically decreased bilateral nigrostriatal system, including bilateral putamen and caudate nuclei. The scintigraphic findings may reflect normal aging or atypical parkinsonism. The bilateral frontal bones and left temporal bone exhibited increased uptake of 99m Tc-TRODAT-1, and previous 99m Tc-MDP bone scan and CT images were reviewed. Osteolytic lesions at the corresponding site indicated bone metastasis from breast cancer., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Papaya leaves have been used as food and traditional herbs for the treatment of cancer, diabetes, asthma, and virus infections, but the active principle has not been understood. We hypothesized that the anti-inflammatory activity could be the predominant underlying principle. To test this, we extracted papaya leaf juice with different organic solvents and found that the ethyl acetate (EA) fraction showed the most outstanding anti-inflammatory activity by suppressing the production of nitric oxide (NO, IC 50 = 24.94 ± 2.4 μg/mL) and the expression of pro-inflammatory enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), and cytokines including interleukins (IL-1β and IL-6), and a tumor necrosis factor (TNF-α) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Transcriptomic analysis and Western blot results revealed its anti-inflammatory mechanisms were through the MAPK signaling pathway by inhibiting the phosphorylation of ERK1/2, JNKs, and p38 and the prevention of the cell surface expression of TLR4. Furthermore, we discovered that the EA fraction could inhibit the replication of alpha-coronavirus (HCoV-229E) and beta-coronavirus (HCoV-OC43 and SARS-CoV-2) and might be able to prevent cytokine storms caused by the coronavirus infection. From HPLC-QTOF-MS data, we found that the predominant phytochemicals that existed in the EA fraction were quercetin and kaempferol glycosides and carpaine. Counter-intuitively, further fractionation resulted in a loss of activity, suggesting that the synergistic effect of different components in the EA fraction contribute to the overall potent activity. Taken together, our results provide preliminary evidence for papaya leaf as a potential anti-inflammatory and anti-coronavirus agent, warranting further study for its use for human health promotion.

Background: There are limited studies that explored the preparation and challenges faced by standardized patients (SPs) in portraying characters in difficult communication scenarios, and the strategies used to overcome these challenges. The purpose of this study was to understand the experience of SPs in interpreting difficult communication situations and the learning needs of performing similar scenarios. And it allows the researchers to explore the meaning, beliefs, values, and aspiration associated with their role as SPs. The findings could shade light on the significance of their experiences and provide valuable insights for the development of future SP training programs., Methods: The design of this study is framed by a narrative inquiry, using semi-structured guidelines to conduct in-depth interviews with 11 SPs who have participated in the performances of difficult communication situations. Research data were analyzed by Polkinghorne narrative analysis, and Riessman's four criteria were used to establish rigor., Results: Analysis revealed the following five themes: scenarios to real life connections, process of preparing for a performance, methods to detach from character, obtaining unexpected rewards, and needs for performance training. There are two to three subthemes that are subsumed under each theme., Conclusions: To strengthen training in difficult communication for healthcare professionals, the use of SPs to interpret challenging difficult communication scenarios will continue to increase. Educators need to ensure that SPs are fully prepared physically and emotionally before, during and after their performance. Offering of continuing education and training in feedback techniques are crucial to extend the tenure of SPs, reduce their frustration, prevent attrition, and ultimately, reduce training costs. In the future, SP training should also include detachment and feedback techniques to alleviate SPs' stress.

We report results from an analysis aimed at detecting the trispectrum of the kinematic Sunyaev-Zel'dovich (kSZ) effect by combining data from the South Pole Telescope (SPT) and Herschel-SPIRE experiments over a 100  deg^{2} field. The SPT observations combine data from the previous and current surveys, namely SPTpol and SPT-3G, to achieve depths of 4.5, 3, and 16  μK-arcmin in bands centered at 95, 150, and 220 GHz. For SPIRE, we include data from the 600 and 857 GHz bands. We reconstruct the velocity-induced large-scale correlation of the small-scale kSZ signal with a quadratic estimator that uses two cosmic microwave background (CMB) temperature maps, constructed by optimally combining data from all the frequency bands. We reject the null hypothesis of a zero trispectrum at 10.3σ level. However, the measured trispectrum contains contributions from both the kSZ and other undesired components, such as CMB lensing and astrophysical foregrounds, with kSZ being sub-dominant. We use the agora simulations to estimate the expected signal from CMB lensing and astrophysical foregrounds. After accounting for the contributions from CMB lensing and foreground signals, we do not detect an excess kSZ-only trispectrum and use this nondetection to set constraints on reionization. By applying a prior based on observations of the Gunn-Peterson trough, we obtain an upper limit on the duration of reionization of Δz&#95;{re,50}<4.5 (95% confidence level). We find these constraints are fairly robust to foregrounds assumptions. This trispectrum measurement is independent of, but consistent with, Planck's optical depth measurement. This result is the first constraint on the epoch of reionization using the non-Gaussian nature of the kSZ signal.

The mechanisms linking a history of major depressive disorder (MDD) to an increased risk of Alzheimer's disease and related dementia (ADRD) are not fully understood. Using the UK Biobank available proteomic and genomic data, we evaluated the biological mechanisms linking both conditions. In participants with a history of MDD at baseline (n=3,615), we found that plasma levels of NfL, GFAP, PSG1 were associated with higher risk (HR=1.38; 1.37; 1.34, respectively; all adjusted p-values<0.05), while VGF, GET3, and HPGDS were associated with lower risk of incident ADRD (n=150) (HR=0.73; 0.71; 0.66, respectively; all adjusted p-values<0.05) during a mean follow-up of 13.7 years (SD=2.2). Two-sample Mendelian randomization analysis using cis-pQTLs genetic instruments revealed that a lower protein expression of apolipoprotein E and higher IL-10 receptor subunit B were causally linked to incident ADRD. Finally, we developed a Proteomic Risk Score (PrRS MDD-ADRD ), which showed strong discriminative power (C-statistic = 0.84) to identify participants with MDD that developed ADRD upon follow-up. In addition to demonstrating an association between plasma proteins associated with inflammation and future ADRD risk in individuals with MDD, our findings include an element of causality using Mendelian Randomization (MR) and PrRS MDD-ADRD can be useful to identify individuals with the highest risk to develop ADRD in a highly vulnerable population., Competing Interests: Conflict of interest: Dr. Diniz serves as a consultant to Bough Bioscience Inc in an area unrelated to this work. The other authors report no conflict of interest.

Objectives: The objective of this study was to evaluate if there are any morphologic, positional, and volumetric differences in the temporomandibular joint (TMJ) of patients with unilateral posterior crossbite (UPC) compared to controls. Another objective was to analyse the discrepancy in the TMJ between the crossbite versus non-crossbite side in UPC versus right and left sides in controls. Additionally, this study aimed to evaluate the differences in the bone density at the masseteric insertion site at the angle of mandible in the UPC group and control group., Material and Methods: One hundred and thirty-two CBCTs were analysed with 66 patients in UPC group and 66 patients in control group (non-crossbite). Temporomandibular joint spaces - Anterior joint space (AJS), Superior joint space (SJS), Posterior joint space (PJS), Medial joint space (MJS), Middle joint space (MiJS), and Lateral joint space (LJS) were measured. Additionally, bone density at angle of mandible and volume of mandibular condyle were evaluated. The measurements were compared between the groups as well as between the crossbite and non-crossbite sides within the UPC group and between right and left sides within the control group. Furthermore, the associations between UPC and changes in TMJ regarding joint space availability, bone density, condylar head volume, and the effects of sex and age were evaluated using regression analysis., Results: It was observed that UPC group showed a greater condylar volume, than the control group. Additionally, a larger mean discrepancy was observed between the crossbite side and non-crossbite side within the UPC group concerning condylar volume than controls. Concerning age, condylar volume was observed to be larger in adults than children. Adults showed significantly greater bone density and condylar volume than adolescents. Concerning sex, it was observed that males showed a larger SJS (right), MiJS, LJS, and bone density at the mandibular angle than females., Conclusion: There is a difference in the TMJ parameters particularly condylar volume in patients with UPC compared to controls., (Copyright © 2024 CEO. Published by Elsevier Masson SAS. All rights reserved.)

We employed first-principles calculations to investigate the effect of chemical doping on the lithiation kinetics and dynamic properties of the c-Si anode. Our ab initio molecular dynamics simulations reveal that phosphorous/arsenic doping can greatly enhance the lithiation kinetics of c-Si, whereas boron doping is unable to produce such an improvement. Our calculations also show that boron doping could enhance Li insertion into c-Si, but phosphorous/arsenic doping tends to increase the insertion energy of Li ions. Although the migration energy barriers of Li ions may slightly increase (decrease) in the boron-(phosphorus-/arsenic-)doped c-Si, these changes were only effective within the range of the nearest-neighbor distance from dopants. Furthermore, it was found that the phosphorus-/arsenic-doped Si can be more ductile and can more easily undergo plastic deformation upon lithiation, while the c-Si matrix becomes more brittle and stiffer when doped with boron. Our simulation results also demonstrate that phosphorous- and arsenic-doping can effectively speed up the Li-induced structural amorphization of c-Si while boron doping appears to severely slow it down. These findings unambiguously indicate that the induced mechanical softening of the c-Si bond network can be the primary factor that leads to the enhanced lithiation kinetics in the n-type doped c-Si anodes., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Aim: Sphingolipids are a class of complex and bioactive lipids that are involved in the pathological processes of cardiovascular disease. Fabry disease is an X-linked storage disorder that results in the pathological accumulation of glycosphingolipids in body fluids and the heart. Cardiac dyssynchrony is observed in patients with Fabry disease and left ventricular (LV) hypertrophy. However, little information is available on the relationship between plasma sphingolipid metabolites and LV remodelling after acute myocardial infarction (AMI). The purpose of this study was to assess whether the baseline plasma sphingomyelin/acid ceramidase (aCD) ratio predicts LV dyssynchrony at 6M after AMI., Methods: A total of 62 patients with AMI undergoing primary angioplasty were recruited. Plasma aCD and sphingomyelin were measured prior to primary angioplasty. Three-dimensional echocardiographic measurements of the systolic dyssynchrony index (SDI) were performed at baseline and 6 months of follow-up. The patients were divided into three groups according to the level of aCD and sphingomyelin above or below the median. Group 1 denotes lower aCD and lower sphingomyelin; Group 3 denotes higher aCD and higher sphingomyelin. Group 2 represents different categories of patients with aCD and sphingomyelin. Trend analysis showed a significant increase in the SDI from Group 1 to Group 3. Logistic regression analysis showed that the sphingomyelin/aCD ratio was a significant predictor of a worsening SDI at 6 months., Conclusions: AMI patients with high baseline plasma sphingomyelin/aCD ratios had a significantly increased SDI at six months. The sphingomyelin/aCD ratio can be considered as a surrogate marker of plasma ceramide load or inefficient ceramide metabolism. Plasma sphingolipid pathway metabolism may be a new biomarker for therapeutic intervention to prevent adverse remodelling after MI.

Background: Colorectal cancer remains a major global public health challenge. Its incidence is shaped by a complex interplay of screening programmes and age, period and cohort factors., Methods: We introduce a novel Age-Period-Cohort-Screening (APCS) model to analyse trends in colorectal cancer incidence in Taiwan from 2000 to 2019., Results: In 2010, the incidence of colorectal cancer in Taiwan increased by 19.2% (95% CI: 13.5%, 25.3%) for men and 15.6% (95% CI: 9.2%, 22.4%) for women. This was followed by annual declines of 3.4% (95% CI: 2.8%, 4.1%) and 3.1% (95% CI: 2.4%, 3.9%), respectively. By 2015 for men and 2014 for women, the age-standardized incidence had fallen below the levels projected in a no-screening scenario. By 2019, the incidence had further declined by 12.4% (95% CI: 11.8%, 13.1%) for men and 11.6% (95% CI: 10.7%, 12.6%) for women, compared with the no-screening scenario. Cohort effects have shown a persistent rise from 1920 to 1980: incidence increased 5.8-fold for men and 3.1-fold for women. The trend began to plateau after 1980, with a noticeable decline in women., Conclusion: Through its screening programme, Taiwan has successfully reduced colorectal cancer incidence by 10% as of 2019. Furthermore, the incidence due to cohort effects has plateaued and even begun to decline. However, continued monitoring remains crucial. The advanced APCS model could serve as a robust analytical tool for other researchers and policy makers evaluating the impacts of cancer screening programmes on incidence trends., (© The Author(s) 2024; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Mitochondria play important roles in cell fate, calcium signaling, mitophagy, and the signaling through reactive oxygen species (ROS). Recently, mitochondria are considered as a signaling organelle in the cell and communicate with other organelles to constitute the mitochondrial information processing system (MIPS) that transduce input-to-output biological information. The success in immunotherapy, a concept of systemic therapy, has been proved to be dependent on paracrine interactions within the tumor microenvironment (TME) and distant organs including microbiota and immune components. We will adopt a broader view from the concept of TME to tumor micro- and macroenvironment (T M 2 E) or tumor-organ ecosystem (TOE). In this review, we will discuss the role of mitochondrial signaling by mitochondrial ROS, calcium flux, metabolites, mtDNA, vesicle transportation, and mitochondria-derived peptide in the TME and TOE, in particular immune regulation and effective cancer immunotherapy., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s).)