Specialized replication mechanisms maintain genome stability at human centromeres.

The high incidence of whole-arm chromosome aneuploidy and translocations in tumors suggests instability of centromeres, unique loci built on repetitive sequences and essential for chromosome separation. The causes behind this fragility and the mechanisms preserving centromere integrity remain elusive. We show that replication stress, hallmark of pre-cancerous lesions, promotes centromeric breakage in mitosis, due to spindle forces and endonuclease activities. Mechanistically, we unveil unique dynamics of the centromeric replisome distinct from the rest of the genome. Locus-specific proteomics identifies specialized DNA replication and repair proteins at centromeres, highlighting them as difficult-to-replicate regions. The translesion synthesis pathway, along with other factors, acts to sustain centromere replication and integrity. Prolonged stress causes centromeric alterations like ruptures and translocations, as observed in ovarian cancer models experiencing replication stress. This study provides unprecedented insights into centromere replication and integrity, proposing mechanistic insights into the origins of centromere alterations leading to abnormal cancerous karyotypes.

Giant magnetocaloric effect in spin supersolid candidate Na2BaCo(PO4)2.

Supersolid, an exotic quantum state of matter that consists of particles forming an incompressible solid structure while simultaneously showing superfluidity of zero viscosity1, is one of the long-standing pursuits in fundamental research2,3. Although the initial report of 4He supersolid turned out to be an artefact4, this intriguing quantum matter has inspired enthusiastic investigations into ultracold quantum gases5-8. Nevertheless, the realization of supersolidity in condensed matter remains elusive. Here we find evidence for a quantum magnetic analogue of supersolid-the spin supersolid-in the recently synthesized triangular-lattice antiferromagnet Na2BaCo(PO4)2 (ref. 9). Notably, a giant magnetocaloric effect related to the spin supersolidity is observed in the demagnetization cooling process, manifesting itself as two prominent valley-like regimes, with the lowest temperature attaining below 100 mK. Not only is there an experimentally determined series of critical fields but the demagnetization cooling profile also shows excellent agreement with the theoretical simulations with an easy-axis Heisenberg model. Neutron diffractions also successfully locate the proposed spin supersolid phases by revealing the coexistence of three-sublattice spin solid order and interlayer incommensurability indicative of the spin superfluidity. Thus, our results reveal a strong entropic effect of the spin supersolid phase in a frustrated quantum magnet and open up a viable and promising avenue for applications in sub-kelvin refrigeration, especially in the context of persistent concerns about helium shortages10,11.

Flavivirus genome recoding by codon optimisation confers genetically stable in vivo attenuation in both mice and mosquitoes.

Virus genome recoding is an attenuation method that confers genetically stable attenuation by rewriting a virus genome with numerous silent mutations. Prior flavivirus genome recoding attempts utilised codon deoptimisation approaches. However, these codon deoptimisation approaches act in a species dependent manner and were unable to confer flavivirus attenuation in mosquito cells or in mosquito animal models. To overcome these limitations, we performed flavivirus genome recoding using the contrary approach of codon optimisation. The genomes of flaviviruses such as dengue virus type 2 (DENV2) and Zika virus (ZIKV) contain functional RNA elements that regulate viral replication. We hypothesised that flavivirus genome recoding by codon optimisation would introduce silent mutations that disrupt these RNA elements, leading to decreased replication efficiency and attenuation. We chose DENV2 and ZIKV as representative flaviviruses and recoded them by codon optimising their genomes for human expression. Our study confirms that this recoding approach of codon optimisation does translate into reduced replication efficiency in mammalian, human, and mosquito cells as well as in vivo attenuation in both mice and mosquitoes. In silico modelling and RNA SHAPE analysis confirmed that DENV2 recoding resulted in the extensive disruption of genomic structural elements. Serial passaging of recoded DENV2 resulted in the emergence of rescue or adaptation mutations, but no reversion mutations. These rescue mutations were unable to rescue the delayed replication kinetics and in vivo attenuation of recoded DENV2, demonstrating that recoding confers genetically stable attenuation. Therefore, our recoding approach is a reliable attenuation method with potential applications for developing flavivirus vaccines.

Colossal Zero-Field-Cooled Exchange Bias via Tuning Compensated Ferrimagnetic in Kagome Metals.

Exchange bias (EB) is a crucial property with widespread applications but particularly occurs by complex interfacial magnetic interactions after field cooling. To date, intrinsic zero-field-cooled EB (ZEB) has only emerged in a few bulk frustrated systems and their magnitudes remain small yet. Here, enabled by high temperature synthesis, we uncover a colossal ZEB field of 4.95 kOe via tuning compensated ferrimagnetism in a family of kagome metals, which is almost twice the magnitude of known materials. Atomic-scale structure, spin dynamics, and magnetic theory revealed that these compensated ferrimagnets originate from significant antiferromagnetic exchange interactions embedded in the holmium-iron ferrimagnetic matrix due to supersaturated preferential manganese doping. A random antiferromagnetic order of manganese sublattice sandwiched between ferromagnetic iron kagome bilayers accounts for such unconventional pinning. The outcome of the present study outlines disorder-induced giant bulk ZEB and coercivity in layered frustrated systems.

Bacterial polyynes uncovered: a journey through their bioactive properties, biosynthetic mechanisms, and sustainable production strategies.

Covering: up to 2023Conjugated polyynes are natural compounds characterized by alternating single and triple carbon-carbon bonds, endowing them with distinct physicochemical traits and a range of biological activities. While traditionally sourced mainly from plants, recent investigations have revealed many compounds originating from bacterial strains. This review synthesizes current research on bacterial-derived conjugated polyynes, delving into their biosynthetic routes, underscoring the variety in their molecular structures, and examining their potential applications in biotechnology. Additionally, we outline future directions for metabolic and protein engineering to establish more robust and stable platforms for their production.

Enhanced Calvarial Bone Repair Using ASCs Engineered with RNA-Guided Split dCas12a System that Co-Activates Sox 5, Sox6, and Long Non-Coding RNA H19.

Healing of large calvarial bone defects remains challenging. An RNA-guided Split dCas12a system is previously harnessed to activate long non-coding RNA H19 (lncRNA H19, referred to as H19 thereafter) in bone marrow-derived mesenchymal stem cells (BMSCs). H19 activation in BMSCs induces chondrogenic differentiation, switches bone healing pathways, and improves calvarial bone repair. Since adipose-derived stem cells (ASCs) can be harvested more easily in large quantity, here it is aimed to use ASCs as an alternative cell source. However, H19 activation alone using the Split dCas12a system in ASCs failed to elicit evident chondrogenesis. Therefore, split dCas12a activators are designed more to co-activate other chondroinductive transcription factors (Sox5, Sox6, and Sox9) to synergistically potentiate differentiation. It is found that co-activation of H19/Sox5/Sox6 in ASCs elicited more potent chondrogenic differentiation than activation of Sox5/Sox6/Sox9 or H19 alone. Co-activating H19/Sox5/Sox6 in ASCs significantly augmented in vitro cartilage formation and in vivo calvarial bone healing. These data altogether implicated the potentials of the Split dCas12a system to trigger multiplexed gene activation in ASCs for differentiation pathway reprogramming and tissue regeneration.

Auto-inducible synthetic pathway in E. coli enhanced sustainable indigo production from glucose.

Indigo is widely used in textile industries for denim garments dyeing and is mainly produced by chemical synthesis which, however, raises environmental sustainability issues. Bio-indigo may be produced by fermentation of metabolically engineering bacteria, but current methods are economically incompetent due to low titer and the need for an inducer. To address these problems, we first characterized several synthetic promoters in E. coli and demonstrated the feasibility of inducer-free indigo production from tryptophan using the inducer-free promoter. We next coupled the tryptophan-to-indigo and glucose-to-tryptophan pathways to generate a de novo glucose-to-indigo pathway. By rational design and combinatorial screening, we identified the optimal promoter-gene combinations, which underscored the importance of promoter choice and expression levels of pathway genes. We thus created a new E. coli strain that exploited an indole pathway to enhance the indigo titer to 123 mg/L. We further assessed a panel of heterologous tryptophan synthase homologs and identified a plant indole lyase (TaIGL), which along with modified pathway design, improved the indigo titer to 235 mg/L while reducing the tryptophan byproduct accumulation. The optimal E. coli strain expressed 8 genes essential for rewiring carbon flux from glucose to indole and then to indigo: mFMO, ppsA, tktA, trpD, trpC, TaIGL and feedback-resistant aroG and trpE. Fed-batch fermentation in a 3-L bioreactor with glucose feeding further increased the indigo titer (≈965 mg/L) and total quantity (≈2183 mg) at 72 h. This new synthetic glucose-to-indigo pathway enables high-titer indigo production without the need of inducer and holds promise for bio-indigo production.

Establish and validate the reliability of predictive models in bone mineral density by deep learning as examination tool for women.

While FRAX with BMD could be more precise in estimating the fracture risk, DL-based models were validated to slightly reduce the number of under- and over-treated patients when no BMD measurements were available. The validated models could be used to screen for patients at a high risk of fracture and osteoporosis. PURPOSE: Fracture risk assessment tool (FRAX) is useful in classifying the fracture risk level, and precise prediction can be achieved by estimating both clinical risk factors and bone mineral density (BMD) using dual X-ray absorptiometry (DXA). However, DXA is not frequently feasible because of its cost and accessibility. This study aimed to establish the reliability of deep learning (DL)-based alternative tools for screening patients at a high risk of fracture and osteoporosis. METHODS: Participants were enrolled from the National Bone Health Screening Project of Taiwan in this cross-sectional study. First, DL-based models were built to predict the lowest T-score value in either the lumbar spine, total hip, or femoral neck and their respective BMD values. The Bland-Altman analysis was used to compare the agreement between the models and DXA. Second, the predictive model to classify patients with a high fracture risk was built according to the estimated BMD from the first step and the FRAX score without BMD. The performance of the model was compared with the classification based on FRAX with BMD. RESULTS: Approximately 10,827 women (mean age, 65.4 ± 9.4 years) were enrolled. In the prediction of the lumbar spine BMD, total hip BMD, femoral neck BMD, and lowest T-score, the root-mean-square error (RMSE) was 0.099, 0.089, 0.076, and 0.68, respectively. The Bland-Altman analysis revealed a nonsignificant difference between the predictive models and DXA. The FRAX score with femoral neck BMD for major osteoporotic fracture risk was 9.7% ± 6.7%, whereas the risk for hip fracture was 3.3% ± 4.6%. Comparison between the classification of FRAX with and without BMD revealed the accuracy rate, positive predictive value (PPV), and negative predictive value (NPV) of 78.8%, 64.6%, and 89.9%, respectively. The area under the receiver operating characteristic curve (AUROC), accuracy rate, PPV, and NPV of the classification model were 0.913 (95% confidence interval: 0.904-0.922), 83.5%, 71.2%, and 92.2%, respectively. CONCLUSION: While FRAX with BMD could be more precise in estimating the fracture risk, DL-based models were validated to slightly reduce the number of under- and over-treated patients when no BMD measurements were available. The validated models could be used to screen for patients at a high risk of fracture and osteoporosis.

Annealing-Tunable Charge Density Wave in the Magnetic Kagome Material FeGe.

The unprecedented phenomenon that a charge density wave (CDW) emerges inside the antiferromagnetic (AFM) phase indicates an unusual CDW mechanism associated with magnetism in FeGe. Here, we demonstrate that both the CDW and magnetism of FeGe can be effectively tuned through postgrowth annealing treatments. Instead of the short-range CDW reported earlier, a long-range CDW order is realized below 110 K in single crystals annealed at 320 °C for over 48 h. The CDW and AFM transition temperatures appear to be inversely correlated with each other. The onset of the CDW phase significantly reduces the critical field of the spin-flop transition, whereas the CDW transition remains stable against minor variations in magnetic orders such as annealing-induced magnetic clusters and spin-canting transitions. Single-crystal x-ray diffraction measurements reveal substantial disorder on the Ge1 site, which is characterized by displacement of the Ge1 atom from the Fe_{3}Ge layer along the c axis and can be reversibly modified by the annealing process. The observed annealing-tunable CDW and magnetic orders can be well understood in terms of disorder on the Ge1 site. Our study provides a vital starting point for the exploration of the unconventional CDW mechanism in FeGe and of kagome materials in general.

Gold Fluorescence Nanoparticles for Enhanced SERS Detection in Biomedical Sensor Applications: Current Trends and Future Directions.

Nanotechnology has emerged as a pivotal tool in biomedical research, particularly in developing advanced sensing platforms for disease diagnosis and therapeutic monitoring. Since gold nanoparticles are biocompatible and have special optical characteristics, they are excellent choices for surface-enhanced Raman scattering (SERS) sensing devices. Integrating fluorescence characteristics further enhances their utility in real-time imaging and tracking within biological systems. The synergistic combination of SERS and fluorescence enables sensitive and selective detection of biomolecules at trace levels, providing a versatile platform for early cancer diagnosis and drug monitoring. In cancer detection, AuNPs facilitate the specific targeting of cancer biomarkers, allowing for early-stage diagnosis and personalized treatment strategies. The enhanced sensitivity of SERS, coupled with the tunable fluorescence properties of AuNPs, offers a powerful tool for the identification of cancer cells and their microenvironment. This dual-mode detection not only improves diagnostic accuracy but also enables the monitoring of treatment response and disease progression. In drug detection, integrating AuNPs with SERS provides a robust platform for identifying and quantifying pharmaceutical compounds. The unique spectral fingerprints obtained through SERS enable the discrimination of drug molecules even in complex biological matrices. Furthermore, the fluorescence property of AuNPs makes it easier to track medication distribution in real-time, maximizing therapeutic effectiveness and reducing adverse effects. Furthermore, the review explores the role of gold fluorescence nanoparticles in photodynamic therapy (PDT). By using the complementary effects of targeted drug release and light-induced cytotoxicity, SERS-guided drug delivery and photodynamic therapy (PDT) can increase the effectiveness of treatment against cancer cells. In conclusion, the utilization of gold fluorescence nanoparticles in conjunction with SERS holds tremendous potential for revolutionizing cancer detection, drug analysis, and photodynamic therapy. The dual-mode capabilities of these nanomaterials provide a multifaceted approach to address the challenges in early diagnosis, treatment monitoring, and personalized medicine, thereby advancing the landscape of biomedical applications.

Cationic Ir(III) Complexes with 4-Fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile as the Cyclometalating Ligand: Synthesis, Characterizations, and Application to Ultrahigh-Efficiency Light-Emitting Electrochemical Cells.

Light-emitting electrochemical cells (LECs) promise low-cost, large-area luminescence applications with air-stabilized electrodes and a versatile fabrication that enables the use of solution processes. Nevertheless, the commercialization of LECs is still encountering many obstacles, such as low electroluminescence (EL) efficiencies of the ionic materials. In this paper, we propose five blue to yellow ionic Ir complexes possessing 4-fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile (ppfn) as a novel cyclometalating ligand and use them in LECs. In particular, the device within di[4-fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile]-4,4'-di-tert-butyl-2,2'-bipyridyl iridium(III) hexafluorophosphate (DTBP) shows a remarkable photoluminescence quantum yield (PLQY) of 70%, and by adjusting the emissive-layer thickness, the maximal external quantum efficiency (EQE) reaches 22.15% at 532 nm under the thickness of 0.51 µm, showing the state-of-the-art value for the reported blue-green LECs.

Review on demulsification techniques for oil/water emulsion: Comparison of recyclable and irretrievable approaches.

Since the establishment of the first global refinery in 1856, crude oil has remained one of the most lucrative natural resources worldwide. However, during the extraction process from reservoirs, crude oil gets contaminated with sediments, water, and other impurities. The presence of pressure, shear forces, and surface-active compounds in crude oil leads to the formation of unwanted oil/water emulsions. These emulsions can take the form of water-in-oil (W/O) emulsions, where water droplets disperse continuously in crude oil, or oil-in-water (O/W) emulsions, where crude oil droplets are suspended in water. To prevent the spread of water and inorganic salts, these emulsions need to be treated and eliminated. In existing literature, different demulsification procedures have shown varying outcomes in effectively treating oil/water emulsions. The observed discrepancies have been attributed to various factors such as temperature, salinity, pH, droplet size, and emulsifier concentrations. It is crucial to identify the most effective demulsification approach for oil/water separation while adhering to environmental regulations and minimizing costs for the petroleum sector. Therefore, this study aims to explore and review recent advancements in two popular demulsification techniques: chemical demulsification and magnetic nanoparticles-based (MNP) demulsification. The advantages and disadvantages of each technique are assessed, with the magnetic approach emerging as the most promising due to its desirable efficiency and compliance with environmental and economic concerns. The findings of this report are expected to have a significant impact on the overall process of separating oil and water, benefiting the oil and gas industry, as well as other relevant sectors in achieving the circular economy.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

The association between sleep quantity, insomnia and lung cancer risk - A systematic review and meta-analysis.

PURPOSE: The effect of various sleep traits on the risk of lung cancer differs among pre-existing studies. This study aims to systematically review and synthesise the association between sleep duration and insomnia with the incidence of lung cancer. METHODS: PubMed, Embase and The Cochrane Library were searched from inception to 23 April 2023 for observational studies examining the effect of sleep quantity or insomnia on lung cancer incidence. We pooled maximally-adjusted hazard ratios and odds ratios separately using random effects inverse variance weighted models. The risk of bias of observational studies was assessed using the Newcastle-Ottawa Scale. RESULTS: We included 11 observational studies with a pooled cohort of 5,049,141 patients. The mean age of the patients was 49.5 ± 17.7 years, and 51.4% were males. The risk of bias ranged from low-moderate. Individuals who slept for a shorter or longer duration than the reference range of sleep per night showed an increased risk of lung cancer by 11% (HR:1.11; 95%CI:1.00-1.23) and 16% (HR:1.16; 95%CI:1.06-1.27) respectively. Furthermore, individuals with insomnia symptoms had a 9% greater risk of lung cancer than those without symptoms (HR:1.09; 95%CI:1.05-1.13). CONCLUSION: This study suggests that insufficient sleep, excessive sleep and insomnia may be associated with an increased risk of lung cancer. Physicians should be mindful of this association and encourage healthy sleep practises among patients. Given the observed heterogeneity among some pre-existing studies, future research with longer periods of follow-up, greater control for covariates and objective testing of sleep parameters may add value to this topic.

Long-term exposure to NO2 and PM2.5 and the occurrence of chronic kidney disease among patients with type 2 diabetes in Taiwan.

BACKGROUND: Individuals diagnosed with type 2 diabetes (T2D) frequently exhibit chronic kidney disease (CKD) which may be caused by environmental hazards such as exposure to air pollutants. However, limited research has explored the effects of prolonged exposure to air pollutants on CKD development in this population. This study examines the relationship between long-term exposure to air pollutants and CKD incidence in a longitudinal cohort of individuals with type 2 diabetes in Taiwan METHODS: Between 2003 and 2005, we recruited 1316 T2D patients (693 females [52.66 %]; mean age 56.16 ± 8.97 years). Patients were followed until December 31, 2012, with at least two clinical visits. Baseline demographics, medical history, and biomarker levels were collected. The development of CKD was determined by eGFR level < 60 mL/min/1.73 m2. Monthly averages of nitrogen dioxide (NO2) and fine particulate matter [PM ≤ 2.5 µm in aerodynamic diameter (PM2.5)] were acquired from 72 ambient air monitoring stations. The kriging method was employed to estimate the exposure levels to PM2.5, NO2, temperature, and relative humidity in the participants' residential areas. Cox regression with time-dependent covariates regression was applied to assess the impact of long-term exposure to air pollutants and CKD risk. RESULTS: Of 992 patients with normal renal function at baseline, 411 (41.43 %) experienced CKD occurrence over a median follow-up period of 5.45 years. The incidence of CKD was 93.96 cases per 1000 person-years. In multivariable adjusted models, patients exposed to PM2.5 levels above the third quartile of (>33.44 µg/m3) and NO2 levels above the fourth quartile (>22.55 ppb) were found to have an increased risk of CKD occurrence compared to lower exposure levels. CONCLUSIONS: This longitudinal study highlights the increased risk of CKD in individuals with type 2 diabetes due to prolonged exposure to NO2 and PM2.5, emphasizing the need for tailored air quality management strategies for this high-risk population.

Direct Z-scheme Cu2O/WO3/TiO2 nanocomposite as a potential supercapacitor electrode and an effective visible-light-driven photocatalyst.

This paper presents the synthesis of visible light-responsive ternary nanocomposites composed of cuprous oxide (Cu2O), tungsten trioxide (WO3), and titanium dioxide (TiO2) with varying weight percentages (wt.%) of the Cu2O. The resulting Cu2O/WO3/TiO2 (CWT) nanocomposites exhibited band gap energy ranging from 2.35 to 2.90 eV. Electrochemical and photoelectrochemical (PEC) studies confirmed a reduced recombination rate of photoexcited charge carriers in the CWT nanocomposites, facilitated by a direct Z-scheme heterojunction. The 0.50CWT nanocomposite demonstrated superior photodegradation activity (2.29 × 10-2 min-1) against Reactive Black 5 (RB5) dye under visible light activation. Furthermore, the 0.50CWT nanocomposite exhibited excellent stability with 80.51% RB5 photodegradation retention after five cycles. The 0.50CWT electrode achieved a maximum specific capacitance of 66.32 F/g at 10 mA/g current density, with a capacitance retention of 95.17% after 1000 charge-discharge cycles, affirming its stable and efficient supercapacitor performance. This was supported by well-defined peaks in cyclic voltammetry (CV) and galvanostatic charge-discharge (GCD) curves, indicating pseudocapacitive properties.

Illness-related communication between siblings and parents of children with chronic illness and life-limiting conditions: A qualitative analysis.

BACKGROUND: Having a brother or sister who has a chronic illness (lasting >6 months and requiring long-term care) or life-limiting condition (LLC; where cure is highly unlikely and the child is expected to die) has major impacts on siblings. Parent-sibling illness-related communication may contribute to siblings' capacity to cope. OBJECTIVES: In this study, we aimed to explore parent-sibling illness-related communication, from the perspectives of parents and siblings. We also aimed to qualitatively compare participants' responses according to illness group (chronic illness vs. LLCs). METHODS: We collected qualitative data from siblings (32 with a brother/sister with a chronic illness, 37 with a brother/sister with an LLC) and parents of a child with a chronic illness (n = 86) or LLC (n = 38) using purpose-designed, open-ended survey questions regarding illness-related communication. We used an inductive qualitative content analysis and matrix coding to explore themes and compare across illness groups. RESULTS: Two-thirds of siblings expressed satisfaction with their family's illness-related communication. Siblings typically reported satisfaction with communication when it was open and age-appropriate, and reported dissatisfaction when information was withheld or they felt overwhelmed with more information than they could manage. Parents generally favored an open communication style with the siblings, though this was more common among parents of children with an LLC than chronic illness. SIGNIFICANCE OF RESULTS: Our findings show that while many siblings shared that they felt satisfied with familial illness-related communication, parents should enquire with the siblings about their communication preferences in order to tailor illness-related information to the child's maturity level, distress, and age.

Multiple energy X-ray imaging of metal oxide particles inside gingival tissues.

BACKGROUND: Periodontal disease affects over 50% of the global population and is characterized by gingivitis as the initial sign. One dental health issue that may contribute to the development of periodontal disease is foreign body gingivitis (FBG), which can result from exposure to some kinds of foreign metal particles from dental products or food. OBJECTIVE: We design a novel, portable, affordable, multispectral X-ray and fluorescence optical microscopic imaging system dedicated to detecting and differentiating metal oxide particles in dental pathological tissues. A novel denoising algorithm is applied. We verify the feasibility and optimize the performance of the imaging system with numerical simulations. METHODS: The designed imaging system has a focused X-ray tube with tunable energy spectra and thin scintillator coupled with an optical microscope as detector. A simulated soft tissue phantom is embedded with 2-micron thick metal oxide discs as the imaged object. GATE software is used to optimize the systematic parameters such as energy bandwidth and X-ray photon number. We have also applied a novel denoising method, Noise2Sim with a two-layer UNet structure, to improve the simulated image quality. RESULTS: The use of an X-ray source operating with an energy bandwidth of 5 keV, X-ray photon number of 108, and an X-ray detector with a 0.5 micrometer pixel size in a 100 by 100-pixel array allowed for the detection of particles as small as 0.5 micrometer. With the Noise2Sim algorithm, the CNR has improved substantially. A typical example is that the Aluminum (Al) target's CNR is improved from 6.78 to 9.72 for the case of 108 X-ray photons with the Chromium (Cr) source of 5 keV bandwidth. CONCLUSIONS: Different metal oxide particles were differentiated using Contrast-to-Noise ratio (CNR) by utilizing four different X-ray spectra.

Effects of post-curing light intensity on the trueness, compressive strength, and resin polymerization characteristics of 3D-printed 3-unit fixed dental prostheses.

PURPOSE: To investigate the effect of different post-curing light intensities on the trueness, compressive strength, and resin polymerization of 3D-printed 3-unit fixed dental prostheses (FPD). MATERIALS AND METHODS: A total of 60 specimens were prepared to support a 3-unit FDP with a deep chamfer marginal design, utilizing computer-aided design and computer-aided manufacturing (CAD-CAM) technology. Light-polymerizing FDP resin with varying light intensities (105, 210, 420, and 840 mW/cm2) was employed for 10 min. Subsequently, trueness assessment, fracture load testing, scanning electron microscopy (SEM) surface examination, and Fourier-Transform Infrared (FTIR) analysis were conducted. A one-way analysis of variance (ANOVA) was performed to ascertain the differences between the experimental groups (p < 0.05). RESULTS: The group exposed to 210 mW/cm2 showed the highest trueness (57.6 ± 2.1 µm), while the 840 mW/cm2 group had the highest deviation (79.3 ± 2.7 µm) (p < 0.001). Significant differences in fracture resistance were found between groups (p < 0.001), with mean fracture strengths of 1149.77 ± 67.81 N, 1264.92 ± 39.06 N, 1331.34 ± 53.62 N, and 1439.93 ± 34.58 N for light intensities of 105, 210, 420, and 840 mW/cm2, respectively (p < 0.001). The resin polymerization analysis shows a peak intensity surge at 3579 cm-1 for O-H and C-H stretching vibrations, except in samples exposed to 105 mw/cm2 light, with the lowest peak at 2890 cm-1. The performance of resin polymerization is most significant under the condition of 840 mW/cm2. CONCLUSION: The light intensity of 210 mW/cm2 exhibited the highest trueness, while the 840 mW/cm2 group showed the highest deviation. However, the light intensity of 840 mW/cm2 demonstrated the highest compressive strength. Furthermore, polymerization occurred at all post-treatment light intensities except 105 mW/cm2. These findings indicate that while low-intensity usage offers greater trueness, high-intensity usage provides better compressive strength and polymerization. Therefore, 210 mW/cm2 could be the recommended solution for post-curing.

Pituitary Adenoma: SSTR2 rs2236750, SSTR5 rs34037914, and AIP rs267606574 Genetic Variants, Serum Levels, and Ki-67 Labeling Index Associations.

Background and Objectives: This study explores the complex pathogenesis of pituitary adenomas (PAs), prevalent intracranial tumors in the pituitary gland. Despite their generally benign nature, PAs exhibit a diverse clinical spectrum involving hormone hypersecretion and varying invasiveness, hinting at multifaceted molecular mechanisms and abnormalities in tumorigenesis and gene regulation. Materials and Methods: The investigation focuses on the Ki-67 labeling index, SSTR2 rs2236750, SSTR5 rs34037914, and AIP rs267606574 polymorphisms, alongside serum levels of SSTR2, SSTR5, and AIP, to discern their association with PAs. The Ki-67 labeling index was assessed using immunohistochemical analysis with the monoclonal antibody clone SP6, representing the percentage of tumor cells showing positive staining. Genotyping was performed via real-time polymerase chain reaction, and serum levels were analyzed using ELISA. The study included 128 PA patients and 272 reference group subjects. Results: The results derived from binary logistic regression analysis revealed an intriguing correlation between the SSTR2 rs2236750 AG genotype and approximately a 1.6-fold increased likelihood of PA occurrence. When analyzing SSTR5 rs34037914, statistically significant differences were found between Micro-PA and the reference group (p = 0.022). Additionally, the SSTR5 rs34037914 TT genotype, compared with CC + CT, under the most robust genetic model (selected based on the lowest AIC value), was associated with a 12-fold increased odds of Micro-PA occurrence. However, it is noteworthy that after applying Bonferroni correction, these findings did not retain statistical significance. Conclusions: Consequently, while this study hinted at a potential link between SSTR2 rs2236750 and pituitary adenoma development, as well as a potential link between SSTR5 rs34037914 and Micro-PA development, it underscored the need for further analysis involving a larger cohort to robustly validate these findings.