Development of aptamer-based lateral flow devices for rapid detection of SARS-CoV-2 S protein and uncertainty assessment.

The outbreak and spread of COVID-19 have highlighted the urgent need for early diagnosis of SARS-CoV-2. Nucleic acid testing as an authoritative tool, is cumbersome, time-consuming, and easy to cross-infect, while the available antibody self-testing kits are deficient in sensitivity and stability. In this study, we developed competitive aptamer-based lateral flow devices (Apt-LFDs) for the quantitative detection of SARS-CoV-2 spike (S) protein. Molecular docking simulation was used to analyze the active binding sites of the aptamer to S protein, guiding complementary DNA (cDNA) design. Then a highly efficient freezing strategy was applied for the conjugation of gold nanoparticles (AuNPs) and DNA probes. Under optimal conditions, the linear range of the constructed Apt-LFDs was 0.1-1 µg/mL, and the limit of detection (LOD) was 51.81 ng/mL. The cross-reactivity test and stability test of the Apt-LFDs showed good specificity and reliability. The Apt-LFDs had recoveries ranging from 89.45 % to 117.12 % in pharyngeal swabs. Notably, the uncertainty of the analytical result was evaluated using a "bottom-up" approach. At a 95 % confidence level, the uncertainty report of (453.37±54.86) ng/mL with k = 2 was yielded. Overall, this study provides an important reference for the convenient and reliable detection of virus proteins based on LFDs.

A U-shaped association between composite dietary antioxidant index and migraine in US adults: a nationwide cross-sectional study.

BACKGROUND: The field of dietary therapies for migraine has grown in popularity. Less research has been conducted to establish the relationship between migraine and the composite dietary antioxidant index (CDAI), a crucial indicator for evaluating the overall combined effects of multiple dietary antioxidants. Therefore, this study addressed this gap based on the National Health and Nutrition Examination Survey (NHANES) database. METHODS: Multivariate logistic regression equations were used to investigate the relationship between CDAI and migraine, and smoothed-fitted curves were plotted. After a nonlinear relationship was discovered, the recursive algorithm and a two-stage linear regression model were employed to calculate the turning point. Additional stratified analyses were performed to explore differences between populations. RESULTS: This study included a total of 9,190 participants aged 20 years old or older. A U-shaped association was observed between the CDAI and migraine, with an inflection point of 0.2. They were negatively correlated before the inflection point with OR of 0.93 (95% CI = 0.88-0.97) and positively correlated after the inflection point with OR of 1.04 (95% CI = 1.01-1.07). This U-shaped relationship persisted among people aged <60 and ≥60 years, women, and people with BMI <30 and ≥30. CONCLUSIONS: We identified a U-shaped association between CDAI and migraine in the U.S. adult population. Further case-control studies and experimental research are needed to explore the underlying mechanisms of action.

Effects of PPARG on the proliferation, apoptosis, and estrogen secretion in goat granulosa cells.

As a member of peroxisome proliferator-activated receptor (PPAR) family, PPARG has been reported to be involved in glucolipid metabolism in various species. However, the function of PPARG in estradiol (E2) synthesis, apoptosis, and proliferation in goat ovarian granulosa cells (GCs) is unclear. In this study, we found that goat PPARG was expressed in GCs of all grades of follicles, and localized in the cytoplasm and nucleus of GCs. Transfection of small interfering RNA-PPARG2 (si-PPARG2) decreased E2 synthesis and the abundances of HSD3B and CYP19A1 mRNA and protein. It also promoted cell apoptosis with significant increases in the ratio of BAX/BCL-2 and Caspase3 mRNA and protein. Meanwhile, cell cycle was inhibited by si-PPARG2 transfection, accompanied by decreased mRNA levels of CDK4, CKD6, MYC, CCND1, CCND2, PCNA, and CCNB, increased mRNA level of P53, and decreased protein levels of CDK4, MYC, and CCND1. Furthermore, PPARG interference affected the mRNA and protein abundances of CREB as well as the phosphorylation of CREB but not PKA. In conclusion, our data suggest that PPARG plays an important role in regulating E2 synthesis, cell apoptosis, and proliferation of goat GCs, including the CREB expression and phosphorylation. These results provide evidences for the in-depth study of PPARG in the regulation of goat GCs function.

Dysregulated GLUT1 results in the pathogenesis of preeclampsia by impairing the function of trophoblast cells.

Preeclampsia (PE) is a common placental-origin complication of pregnancy and a major cause of morbidity and mortality among pregnant women and fetuses. However, its pathogenesis has not been elucidated. Effective strategies for prevention, screening, and treatment are still lacking. Studies have indicated that dysfunction of placental trophoblast cells, such as impaired syncytialization, proliferation, and epithelial-mesenchymal transition processes, plays a crucial role in the development of PE. Glucose transporter 1 (GLUT1) is a key protein regulating glucose transport in placental tissues. However, the effect of GLUT1 on the function of trophoblast cells in PE is not well understood. In this study, we found that GLUT1 expression is reduced in PE placental tissues. GLUT1 promotes the syncytialization process by increasing the glucose uptake ability of BeWo cells. Additionally, GLUT1 promotes the proliferation, migration, and invasion capabilities of HTR-8/SVneo cells by regulating MAPK and PI3K/AKT signaling pathways. Overall, these findings provide a new insight into understanding the biological functions of GLUT1, clarifying the pathogenesis of PE, and identifying diagnostic and therapeutic targets for PE.

Association between advanced lung cancer inflammation index and chronic kidney disease: a cross-sectional study.

Background: Chronic kidney disease (CKD) is one of the common chronic diseases, and malnutrition and inflammation play a key role in the development of CKD. The advanced lung cancer inflammation index (ALI) is a novel index of nutrition and inflammation, and its association with CKD has not yet been clarified. The aim of this study was to explore the potential association between ALI and CKD. Methods: We conducted a cross-sectional survey using data extracted from the National Health and Nutrition Examination Survey (NHANES, 2003-2018). Weighted multivariate logistic regression was used to assess the association between ALI and CKD, and smoothed curve fitting and threshold effect analyses were used to describe the nonlinear association between ALI and CKD. Subgroup analyses were performed to further assess the influence of other covariates on the relationship between ALI and CKD. Results: A total of 39,469 adult participants were included in the study, of whom 7,204 (18.25%) were diagnosed with CKD. After adjusting for multiple confounders, we found a significant negative correlation between ALI and CKD (OR = 0.93; 95%CI, 0.91-0.95; p < 0.0001). The risk of CKD tended to decrease with increasing quartiles of ALI. Smoothed curve fitting showed an L-shaped negative correlation between ALI and CKD. Threshold analysis showed a saturation effect of ALI at the inflection point of 55.09. Subgroup analyses and interaction tests showed that this negative association was maintained across age, sex, race, BMI, diabetes, hypertension, cardiovascular disease, and cancer subgroups (P for interaction >0.05). Conclusion: Our findings suggest a significant correlation between ALI and CKD in the US adult population. However, more large-scale prospective studies are still needed to further confirm our findings.

Transferrin receptor-targeted immunostimulant for photodynamic immunotherapy against metastatic tumors through ß-catenin/CREB interruption.

The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional treatments. In this work, a transferrin receptor (TfR) targeted immunostimulant (PTI) is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting ß-catenin signal pathway. To synthesize PTI, the photosensitizer conjugated TfR targeting peptide moiety (Palmitic-K(PpIX)-HAIYPRH) is unitized to encapsulate the transcription interrupter of ICG-001. On the one hand, the recognition of PTI and TfR can promote drug delivery into tumor cells to destruct primary tumors through photodynamic therapy and initiate an immunogenic cell death with the release of tumor-associated antigens. On the other hand, PTI will interrupt the binding between ß-catenin and cAMP response element-binding protein (CREB), regulating the gene transcription to downregulate programmed death ligand 1 (PD-L1) while upregulating C-C motif chemokine ligand 4 (CCL4). Furthermore, the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration, and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung metastasis. This work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions.

Oxygen-bridged W-Pd atomic pairs enable H2O2 activation for sensitive immunoassays.

Regulating the performance of peroxidase (POD)-like nanozymes is a prerequisite for achieving highly sensitive and accurate immunoassays. Inspired by natural enzyme catalysis, we design a highly active and selective nanozyme by loading atomically dispersed tungsten (W) sites on Pd metallene (W-O-Pdene) to construct an artificial three-dimensional (3D) catalytic center. The 3D asymmetric W-O-Pd atomic pairs can effectively stretch the O-O bonds in H2O2 and further promote the desorption of H2O to enhance POD-like activity. Moreover, the W-O-Pd sites with unique spatial structures demonstrate satisfactory specificity for H2O2 activation, effectively preventing the interference of dissolved oxygen. Accordingly, the highly active and specific W-O-Pdene nanozymes are utilized for sensitive and accurate prostate-specific antigen (PSA) immunoassay with a low detection limit of 1.92 pg mL-1, superior to commercial enzyme-linked immunosorbent assay.

Developmental Trajectory of Depressive Symptoms among Left-behind Children in Rural China: The Roles of Family Adversity and Personal Growth Initiative.

The adversity faced by left-behind children due to parental migration affects their depressive symptoms, but little is known about the mechanism underlying this association and protective factors from a dynamic perspective. The present study examined the association between family adversity and the developmental trajectory of depressive symptoms, and the potential mediating and moderating role of personal growth initiative in this association among left-behind children. A total of 363 left-behind children (48.8% female; Mage = 12.97 at T1, SDage = 0.55) from five rural middle schools in the Hunan Province of China participated in this three-wave study, employing one-year intervals between assessments. The results indicated the initial level of personal growth initiative mediated the association between family adversity at T1 and the development of depressive symptoms, while the growth rate of personal growth initiative both mediated and moderated this association, with consistent effects across sexes. These findings underscore the critical role of personal growth initiative in the association between family adversity and depressive symptoms among left-behind children.

The impact of alcohol consumption on the relationship between depression and chronic diarrhea: a cross-sectional study analysis on NHANES (2005-2010).

Background: Alcohol consumption, depression, and chronic diarrhea are all public health issues of concern, with irreversible consequences for individual health and significant economic burdens on health care systems. Previous studies have shown that depression increases the risk of developing chronic diarrhea, but few studies have explored whether alcohol consumption has an effect on the relationship between depression and chronic diarrhea. Objective: To explore the effect of alcohol consumption on the relationship between depression and chronic diarrhea. Methods: 12,538 adults (≥20 years) in NHANES from 2005-2010 were analyzed. Participants were stratified according to drinking status, and differences between the risk of depression and chronic diarrhea among participants who drank alcohol or not were assessed using multiple regression analysis and likelihood ratio tests. Results: In this cross sectional, after adding possible confounders, the prevalence of depression with chronic diarrhea was higher in the drinking population than in the non-drinking population (OR,2.34, 95%CI:1.84-2.98 and 1.26, 95%CI:0.85-1.86), with a likelihood ratio test of P=0.024. Conclusion: Our findings suggest that there is a significant association between depression and chronic diarrhea and that alcohol consumption may increase the correlation between depression and chronic diarrhea. However, these findings require further prospective studies to provide more evidence.

Association between weight-adjusted-waist index and gynecologic cancers: a population-based study.

Objective: This study aims to analyze the association between the weight-adjusted waist index (WWI) and the risk of gynecologic cancers, using data collected from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. Methods: We employed multiple logistic regression analysis to investigate the relationship between WWI and risk of gynecologic cancers. Subsequent subgroup analyses were performed on specific populations of interest. A restricted cubic spline model was used to explore potential non-linear relationships. Additionally, the effectiveness of WWI in predicting sarcopenia was assessed through Receiver Operating Characteristic (ROC) curve analysis. K-fold cross-validation was applied for model assessment. Results: Among the 4,144 participants, 98 self-reported having gynecologic cancers. In the fully adjusted model, WWI was significantly associated with the prevalence of gynecologic cancers (OR = 1.38, 95% CI: 1.02-1.88, p = 0.0344). Our findings indicate a linear positive association between WWI and the risk of gynecologic cancers. Subgroup analysis revealed that WWI had the strongest association with cervical cancer (OR = 1.46, 95% CI: 0.97-2.18, p = 0.0354) and endometrial cancer (OR = 1.39, 95% CI: 0.81-2.39, p = 0.0142). No significant association was found between WWI and the risk of ovarian cancer (OR = 1.16, 95% CI: 0.48-2.72, p = 0.5359). Restricted cubic spline analysis confirmed a linear relationship between WWI and the risk of cervical, endometrial, and ovarian cancers. ROC curve analysis demonstrated that WWI had superior predictive capability for gynecologic cancers. Conclusion: Elevated levels of WWI were significantly associated with an increased risk of gynecologic cancers in American women, displaying a stronger association than other obesity markers. Therefore, WWI may serve as a distinct and valuable biomarker for assessing the risk of gynecologic cancers, particularly cervical and endometrial cancers.

Dynamic leaching behaviors of heavy metals from recycled coal gangue aggregate under loading conditions during solid backfill mining.

In solid backfill coal mining, recycled coal gangue aggregate (RCGA) is subject to the combined effects of overlying strata stress and leaching by mine water in the goaf. This process causes heavy metals to be leached and released from RCGA, which can lead to groundwater contamination. In this study, the release patterns of heavy metals in RCGA under the coupled effects of stress, solution pH, and solution flow rate were investigated, and the interactions between RCGA and the surrounding environment were explored. The findings indicate that: (1) The combined action of effective stress and mine water promotes the leaching of heavy metals. Specifically, the leaching of Pb, Zn, and Mn of RCGA is primarily influenced by the pH value of the leaching solution, while the leaching of Cu and Cr of RCGA is more closely related to the stress level; (2) Acidic environments accelerate the release of carbonate-bound fraction (CAR) in elements, facilitating the transformation of Fe/Mn oxide-bound fraction (XXI) into soluble forms; (3) The leaching ratios (Lr) of heavy metals follow the order: LrZn > LrPb > LrMn > LrCu > LrCr. This research provides guidance for the safe application of RCGA in solid backfill coal mining.

Thyroid hormones and oxidative stress moderated the association between urinary phthalate metabolites and cardiovascular risk factors.

While previous studies suggested that phthalate exposure poses a risk to cardiovascular health, the results are mixed and indicated variability based on population characteristics and health outcomes assessed. Research that simultaneously investigates the association between urinary phthalate metabolites and multiple cardiovascular risk factors within a single study is relatively scarce. This study assessed human exposure to phthalates by determining urinary metabolite concentrations, and applied multiple statistical techniques to systematically evaluate the individual dose-response relationships and joint effects of phthalate exposure on blood lipids, blood pressure, and fasting blood glucose. The results revealed significant negative associations between urinary phthalate metabolites and low-density lipoprotein cholesterol, triglycerides, total cholesterol, diastolic blood pressure, systolic blood pressure, and fasting blood glucose. Significant nonlinear associations were obtained between specific individual metabolites and diastolic blood pressure. The oxidative stress biomarker 8-hydroxydeoxyguanosine levels in urine and thyroid hormone levels in paired serum were measured simultaneously. Then, we examined the indirect roles of thyroid hormones and oxidative stress in the association between urinary phthalate metabolites and cardiovascular risk factors by mediation and moderation analysis. While the mediation effect was not statistically significant, the negative associations of urinary phthalate metabolites with fasting blood glucose, triglyceride, and lipoprotein cholesterol were statistically significant at lower levels of thyroid hormones by moderation analysis. The association was also significant under certain levels of oxidative stress. The results demonstrated that phthalate exposure is associated with several cardiovascular risk factors, and maintaining appropriate oxidative stress levels and ensuring sufficient thyroid hormone levels may attenuate these associations.

Simultaneous labial and lingual augmented corticotomy assisted presurgical orthodontics in class III patients: the morphological aspects of the mandibular anterior ridge with cone-beam computed tomography.

OBJECTIVES: This study aims to investigate the changes in alveolar bone following the simultaneous performance of labial and lingual augmented corticotomy (LLAC) in patients with insufficient alveolar bone thickness on both the labial and lingual sides of the mandibular anterior teeth during presurgical orthodontic treatment. MATERIALS AND METHODS: Thirth-five surgical patients with skeletal Class III malocclusion were included: 19 (LLAC group) accepted LLAC surgery during presurgical orthodontic treatment, and 16 (non-surgery group, NS) accepted traditional presurgical orthodontic treatment. Cone-beam computed tomography (CBCT) scans were obtained before treatment (T0) and at the completion of presurgical orthodontic treatment (T1). The amount of vertical alveolar bone and contour area of the alveolar bone in the labial and lingual sides of mandibular incisors were measured. RESULTS: After presurgical orthodontic treatment, the contour area of the alveolar bone at each level on the lingual side and alveolar bone level on both sides decreased significantly in the NS group (P < 0.001). However, the labial and lingual bone contour area at each level and bone level increased significantly in the LLAC group (P < 0.001). The bone formation rate in the lingual apical region was the highest, significantly different from other sites (P < 0.001). CONCLUSIONS: During presurgical orthodontic treatment, LLAC can significantly increase the contour area of the labio-lingual alveolar bone in the mandibular anterior teeth to facilitate safe and effective orthodontic decompensation in skeletal Class III patients. CLINICAL RELEVANCE: This surgery has positive clinical significance in patients lacking bone thickness (< 0.5 mm) in the labial and lingual sides of the lower incisors.

Longitudinal study and predictive modelling of urinary pesticide metabolite concentrations in residents of Guangzhou, China.

Continuous human biomonitoring and predictive modelling of urinary pesticide metabolites are critical for evaluating pesticide exposure trends and associated health risks. We conducted repeat cross-sectional surveys to determine the urinary concentrations of eight pesticide metabolites in the residents of Guangzhou, China, from 2018 to 2022. We longitudinally analyzed the changes in these metabolite concentrations over the years and assessed the potential non-carcinogenic risks by calculating the hazard quotient and hazard index. No significant differences were observed in the total urinary pesticide metabolite concentrations over the 5 years (9.16-12.99 µg/L). The urinary concentrations of 3,5,6-trichloro-2-pyridinol and 2,4-dichlorophenoxyacetic acid reached their lowest levels in 2020 (1.47 and 0.11 µg/L). Conversely, urinary para-nitrophenol concentrations exhibited an inverse trend, peaking in 2020 (6.16 µg/L). The composition profiles of urinary pesticide metabolites showed that para-nitrophenol consistently constituted the largest proportion each year. Males consistently showed higher median concentrations of total urinary pesticide metabolites and individual metabolites of 3,5,6-trichloro-2-pyridinol, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid, and para-nitrophenol than females. The concentrations of cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid in adults' urine were significantly higher than those in minors' urine each year. The total pesticide metabolite concentrations in adults' urine were significantly higher than those in minors' urine in 2018 and 2020, whereas no significant differences were observed in other years. No significant differences in urinary pesticide metabolite concentrations were observed among different BMI groups. Results showed that 14.17% of the population had hazard index values above 1, indicating a higher risk of health hazards. Three predictive models were employed to predict urinary pesticide metabolite concentrations for 2023-2024, revealing an increasing trend in 3,5,6-trichloro-2-pyridinol concentrations while other metabolites are expected to decrease. The study showed the concentration of para-nitrophenol peaked in 2020 while 3,5,6-trichloro-2-pyridinol and 2,4-dichlorophenoxyacetic acid reached their lowest levels, suggests that the COVID-19 pandemic may have influenced pesticide exposure patterns.

Biomimetic Electronic Communication of Iodine Doped Single-Atom Fe Site for Highly Active and Stable Dopamine Oxidation.

Rational design of highly active and stable catalysts for dopamine oxidation is still a great challenge. Herein, inspired by the catalytic pocket of natural enzymes, an iodine (I)-doped single Fe-site catalyst (I/FeSANC) is synthesized to mimic the catalytic center of heme enzymes in both geometrical and electronic structures, aiming to enhance dopamine (DA) oxidation. Experimental studies and theoretical calculations show that electronic communication between I and FeN5 effectively modulates the electronic structure of the active site, greatly optimizing the overlap of Fe 3d and O 2p orbitals, thereby enhancing OH adsorption. In addition, the electronic communication induced by iodine doping attenuates the attack of proton hydrogen on the active center, thereby enhancing the stability of I/FeSANC. This work provides new insights into the design of highly active and stable single-atom catalysts and enhances the understanding of catalytic mechanisms for DA oxidation at the atomic scale.

An Antibacterial, Highly Sensitive Strain Sensor Based on an Anionic Copolymer Interpenetrating with κ-Carrageenan.

Polysaccharide-based hydrogels are suitable for use in the field of flexible bioelectronics due to their benign mechanical properties and biocompatibility. However, the preparation of hydrogel sensors with high performance without affecting their physicochemical properties (e.g., flexibility, toughness, self-healing, and antibacterial activity) remains a challenge and needs to be solved. Herein, a metal ion cross-linking reinforced, double network hydrogel was formed from a 2-acrylamide-2-methylpropanesulfonic acid (AMPS) copolymer interpenetrating κ-carrageenan (CAR), followed by immersing the gel in a Cu2+ ion solution to obtain an antibacterial CAR/P(AM-co-AMPS)-Cu2+ conductive hydrogel. LiCl was added as the electrolyte. The presence of the LiCl electrolyte and sulfonated molecular chain units not only gives the hydrogel good electrical conductivity (conductivity up to 2.68 S/m) but also improves the sensitivity of the hydrogel as a stress-strain sensor, with a hydrogel sensitivity GF of up to 3.76 in the 20%-100% strain range and response time of up to 280 ms. The CAR double-helical structure and sol-gel properties and the interaction of multiple noncovalent bonds between polymers provide the hydrogel with excellent self-healing, with a self-healing efficiency of 68%. In addition, the electrostatic interaction of Cu2+ with Escherichia coli cells can inhibit their growth, exhibiting good antibacterial properties with an inhibition circle diameter of 20.5 mm. This work could provide an effective strategy for antibacterial multifunctional CAR-based bionic sensors.

Comparing sleep measures in cancer survivors: self-reported sleep diary versus objective wearable sleep tracker.

PURPOSE: Cancer survivors are increasingly using wearable fitness trackers, but it is unclear if they match traditional self-reported sleep diaries. We aimed to compare sleep data from Fitbit and the Consensus Sleep Diary (CSD) in this group. METHODS: We analyzed data from two randomized clinical trials, using both CSD and Fitbit to collect sleep outcomes: total sleep time (TST), wake time after sleep onset (WASO), number of awakenings (NWAK), time in bed (TIB), and sleep efficiency (SE). Insomnia severity was measured by Insomnia Severity Index (ISI). We used the Wilcoxon signed rank test, Spearman's rank correlation coefficients, and the Mann-Whitney test to compare sleep outcomes and assess their ability to distinguish insomnia severity levels between CSD and Fitbit data. RESULTS: Among 62 participants, compared to CSD, Fitbit recorded longer TST by an average of 14.6 (SD = 84.9) minutes, longer WASO by an average of 28.7 (SD = 40.5) minutes, more NWAK by an average of 16.7 (SD = 6.6) times per night, and higher SE by an average of 7.1% (SD = 14.4); but shorter TIB by an average of 24.4 (SD = 71.5) minutes. All the differences were statistically significant (all p < 0.05), except for TST (p = 0.38). Moderate correlations were found for TST (r = 0.41, p = 0.001) and TIB (r = 0.44, p < 0.001). Compared to no/mild insomnia group, participants with clinical insomnia reported more NWAK (p = 0.009) and lower SE (p = 0.029) as measured by CSD, but there were no differences measured by Fitbit. CONCLUSIONS: TST was the only similar outcome between Fitbit and CSD. Our study highlights the advantages, disadvantages, and clinical utilization of sleep trackers in oncology.

Genetic Risk Stratification and Outcomes Among Treatment-Naive Patients With AML Treated With Venetoclax and Azacitidine.

European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems were based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. Here, pooled analysis of patients in the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to 2017 and 2022 ELN risk classifications. A bioinformatic algorithm derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on median overall survival (OS). 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. When classified by ELN 2017 or 2022 prognostic criteria, most patients had adverse-risk AML (60.2% and 72.8% for venetoclax-azacitidine and 65.5% and 75.2% for placebo-azacitidine, respectively). While outcomes with venetoclax-azacitidine were improved across all ELN risk groups compared with placebo-azacitidine, ELN classification systems poorly discriminated venetoclax-azacitidine outcomes. By applying a bioinformatic algorithm, new molecular signatures were derived differentiating OS outcomes with venetoclax-azacitidine; the mutational status of TP53, FLT3-ITD, NRAS, and KRAS categorized patients into higher-, intermediate-, and lower-benefit groups (52%, 25%, and 23% of patients, respectively), each associated with a distinct median OS (26.5 months [95% CI, 20.2 to 32.7], 12.1 months [95% CI, 7.3 to 15.2], and 5.5 months [95% CI, 2.8 to 7.6], respectively). ELN prognostic classifiers do not provide clinically meaningful risk stratification of OS outcomes for patients with AML treated with venetoclax-azacitidine. TP53, FLT3-ITD, NRAS, and KRAS mutation status allows classification of these patients into three risk groups with distinct differences in median OS.

Impact of COVID-19 on temporal trends and health risks of urinary metal concentrations among residents of Guangzhou, China.

Long-term biomonitoring of urinary metal ions is an essential tool for the epidemiological assessment of chronic exposure levels, enabling us to track changes in metal exposure over time and better understand its health implications. In this study, we evaluated the temporal trends of urinary metal ions among 1962 residents of Guangzhou, China, from 2018 to 2022. The total metal ion concentrations in the urine of the population did not change significantly between 2018 and 2019. With the onset of the COVID-19 pandemic in 2020, urinary total metal ion concentrations began to decline dramatically, reaching their lowest level in 2021. A rebound in concentrations was observed in 2022, which returned to the initial levels observed in 2018. Urine chromium and cadmium concentrations peaked in 2020, while urinary lead levels were the highest in 2021, and urinary nickel concentrations were the highest in 2022. Males consistently displayed higher urinary concentrations of lead and arsenic throughout each year of the study. Furthermore, minors consistently had higher urinary nickel levels than adults, whereas adults consistently had higher urinary cadmium concentrations than minors. Cluster analyses were conducted annually on urinary metal ions to examine the differences in their distribution and to evaluate changes in metal exposure patterns over time. The Monte Carlo simulations indicate that the whole population exhibits a high non-carcinogenic risk from arsenic exposure and significant carcinogenic risks associated with exposure to nickel, arsenic, chromium, and cadmium. The next two years were predicted by a gray prediction model, and the results are tested using mean absolute percentage error which demonstrating high accuracy.

A nomogram prediction of gingival recession in mandibular incisors of orthodontic-orthognathic treated skeletal class III malocclusion with or without PAOO: A retrospective cohort study.

Background: To assess the alterations in gingival thickness and the occurrence gingival recession subsequent to orthodontic-orthognathic treatment of mandibular incisors in skeletal Class III and identify risk factors associated with gingival recession. Methods: In this retrospective cohort study, we enrolled 33 patients exhibiting skeletal Class III malocclusion, totaling 131 mandibular incisors, who were undergoing orthodontic- orthognathic treatment that did not involve extraction of mandibular teeth. The subjects were categorized into surgery group (S; n = 17; ANB = -5.55 ± 3.26; IOFTN = 4.60 ± 0.51, scores ranging: 4.3-5.3) and non-surgery group (NS; n = 16; ANB = -3.00 ± 4.08; IOFTN = 4.63 ± 0.50, scores ranging: 4.3-5.4), based on if they had history of Periodontally Accelerated Osteogenic Orthodontics surgery (S) or not (NS). Patients in S group received orthognathic surgery about 1-1.5 years after Periodontally Accelerated Osteogenic Orthodontics surgery. Alterations in gingival thickness, gingival recession, and keratinized gingival width were compared before and after orthodontic-orthognathic treatment. Logistic regression analysis was used to construct a gingival recession prediction model and draw nomograms. Results: After orthodontic-orthognathic treatment, the gingival thickness and keratinized gingival width in NS group decreased by 0.15 ± 0.21 mm and 0.74 ± 0.91 mm, whereas those in the S group increased by 0.32 ± 0.28 mm and 2.09 ± 1.51 mm (P < 0.05). After orthodontic-orthognathic, the percentage of gingival recession increased by 47.62 % in NS group, which was 14.77 times that of S group (P < 0.05). Multivariate regression analysis indicated that skeletal Class III patients with a gingival thickness below 0.72 mm, an alveolar bone height exceeding 2.36 mm, and an alveolar bone thickness under 0.45 mm might be at elevated risk for developing gingival recession following orthodontic - orthognathic therapy. Conclusions: Drawing on the findings of our investigation, we concluded the risk of gingival recession of mandibular anterior teeth increased after orthodontic-orthognathic treatment in skeletal Class III, whereas Periodontally Accelerated Osteogenic Orthodontics surgery could significantly improve the periodontal phenotype and prevent gingival recession.