Preoperative markers for identifying CT ≤2 cm solid nodules of lung adenocarcinoma based on image deep learning.

BACKGROUND: The solid pattern is a highly malignant subtype of lung adenocarcinoma. In the current era of transitioning from lobectomy to sublobar resection for the surgical treatment of small lung cancers, preoperative identification of this subtype is highly important for patient surgical approach selection and long-term prognosis. METHODS: A total of 1489 patients with clinical stage IA1-2 primary lung adenocarcinoma were enrolled. Based on patient clinical characteristics and lung imaging features obtained via deep learning, highly correlated diagnostic factors were identified through LASSO regression and decision tree analysis. Subsequently, a logistic model and nomogram were constructed. A restricted cubic spline (RCS) was used to calculate the optimal inflection point of quantitative data and the differences between the groups. RESULTS: The three-dimensional proportion of solid component (PSC), sex, and smoking status was identified as being highly correlated diagnostic factors for solid predominant adenocarcinoma. The logistic model had good prediction efficiency, and the area under the ROC curve was 0.85. Decision curve analysis demonstrated that the application of diagnostic factors can improve patient outcomes. RCS analysis indicated that the proportion of solid adenocarcinomas increased by 4.6 times when the PSC was ≥72%. A PSC of 72% is a good cutoff point. CONCLUSION: The preoperative diagnosis of solid-pattern adenocarcinoma can be confirmed by typical imaging features and clinical characteristics, assisting the thoracic surgeon in developing a more precise surgical plan.

Associations of combined accelerated biological aging and genetic susceptibility with incident dementia: a prospective study in the UK Biobank.

BACKGROUND: Accelerated biological aging has been verified to be a critical risk factor for a number of age-related diseases, but its role in dementia remained unclear. Whether it modified the effects of genetic factors was also unknown. This study evaluated the associations between accelerated biological aging and dementia and the moderating role of accelerated biological aging in the genetic susceptibility to the disease. METHODS: We included 200,731 participants in the UK biobank. Nine clinical blood biomarkers and chronological age were used to calculate Phenotypic age acceleration (PhenoAgeAccel), which is a novel indicator for accelerated biological aging. The associations of PhenoAgeAccel with dementia, both young-onset and late-onset dementia, were assessed by Cox proportional hazard models. Apolipoprotein E (APOE) alleles and polygenic risk scores (PRS) were used to evaluate the genetic risk of dementia. The interactions between genetic susceptibility and biological aging were tested on both multiplicative and additive scales. RESULTS: These findings showed individuals who were in the highest quartile of PhenoAgeAccel had a higher risk with incidence of dementia compared to individuals in the lowest quartile of PhenoAgeAccel (HR: 1.145 (95% CI: 1.050, 1.249)). Individuals with biologically older had a higher risk of dementia than individuals with biologically younger (HR: 1.069 (95% CI: 1.004, 1.138)). Furthermore, compared to individuals with biologically younger and low APOE ε4-related genetic risk, individuals with biologically younger and high APOE ε4-related genetic risk (HR:3.048 (95% CI: 2.811, 3.305)) had a higher risk of dementia than individuals with biologically older and high APOE ε4-related genetic risk (HR: 2.765 (95% CI: 2.523, 3.029)). Meanwhile, referring to low dementia PRS and biologically younger, the risk of dementia increased by 72.7% (HR: 1.727 (95% CI: 1.538, 1.939) in the biologically younger and high PRS group and 58.7% (HR: 1.587 (95% CI: 1.404, 1.793) in the biologically older and high PRS group, respectively. The negative interactions between PhenoAgeAccel with APOE ε4 and PRS were also tested on the additive scale. CONCLUSIONS: Accelerated biological aging could bring the extra risk of dementia but attenuate the effects of genetic risk on dementia. These findings provide insights for precise prevention and intervention of dementia.

Eye care service utilization and associated factors among adults in Debre Berhan Town, North Shewa, Ethiopia, 2023.

Introduction: Globally, the utilization of eye care services varies widely, ranging from 18 to 90%. Low utilization of eye care services can lead to delayed detection of vision problems. However, there are limited data on the proportion of eye care service utilization and its associated factors in Ethiopia at the community level. Objective: The objective of this study was to determine the proportion of eye care service utilization and its associated factors among adults in Debre Birhan town, North Shewa, Ethiopia. Methods: Using a multistage sampling method, a community-based cross-sectional study was conducted on 960 adults in Debre Birhan town from 8 May to 8 June 2023. Binary logistic regression was performed. Variables with a p-value of less than 0.05 were considered significant. Results: A total of 940 study participants participated, resulting in a response rate of 97.9%. The mean age of the participants was 54.67 years (SD ± 8.69). The proportion of good-level eye care service utilization was found to be 32.98% [95% confidence interval (CI): 29.97, 35.99]. Factors positively associated with good-level eye care service utilization included older age [adjusted odds ratio (AOR) = 1.58, 95%CI: 1.00, 2.51], higher educational status (AOR = 2.25, 95%CI: 1.25, 4.06), high family monthly income (AOR = 8.70, 95%CI: 4.99,15.18), awareness of regular eye checkups (AOR = 1.77, 95%CI: 1.15, 2.73), a history of eye disease (AOR = 2.57, 95%CI: 1.77,3.74), health insurance (AOR = 1.99, 95% CI: 1.34, 2.95), and history of spectacle use (AOR = 1.94, 95%CI:1.34, 2.80). Conclusion: The study revealed that the proportion of good-level eye care service utilization was low. Older age, higher educational status, high family monthly income, awareness of regular eye checkups, a history of eye disease, health insurance, and history of spectacle use were significantly associated with a good level of eye care service utilization.

Proportion and risk factors for hospital-acquired venous thromboembolism in children: a systematic review and meta-analysis of data from 20 million individuals in 22 countries.

Background: Hospital-acquired venous thromboembolism (HA-VTE) in children has been widely regarded. Objectives: We aimed to analyze the proportion and risk factors for HA-VTE in hospitalized children. Methods: We conducted a comprehensive systematic search across 4 databases from 1990 to 2023. Cochran Q test was used to evaluate the heterogeneity of the effect sizes of study, and I2 statistic was used to quantify the heterogeneity. Pooled estimates were calculated by the inverse-variance weighted method in a fixed-effect model or a random-effect model when heterogeneity was low (I2 < 25%) or high (I2 > 25%), respectively. Results: In total, 105 original papers and 20,718,294 patients were included in the study, and the proportion of HA-VTE in children was 4.1% (95% CI, 2.9%-5.2%). Although the proportion of venous thromboembolism increased over the various research periods, the differences were not statistically significant. In the subgroup analysis based on country, the proportion of pediatric HA-VTE was lowest in the United Kingdom and highest in Spain, whereas when based on region, the proportion was lowest in Asia and highest in North America. Multiple HA-VTE risk factors were identified, including central venous catheter use, age of >10 years, surgery, injury, infection, obesity, mechanical ventilation, blood transfusion, malignancy, coagulation and hemorrhagic disorders, and length of hospital stay. Conclusion: In this study, we systematically analyzed the proportion and risk factors of HA-VTE in hospitalized children. Our findings provide valuable insights for the prevention and treatment of HA-VTE in pediatric patients.

Study on the composition and properties of EME-SBS-Nano ZnO high modulus asphalt material.

The objective of this research is to address the rut problems in asphalt pavements and to resist the permanent plastic deformation with the increasing heavy traffic loads. In this paper, a new type materials of high modulus asphalt was developed by incorporating styrene-butadiene-styrene (SBS) and zinc oxide nanoparticles (nano ZnO) with an (EME)-type high modulus modifier, guided by the synergistic effects and the preparation methods of High-speed shear. The basic road performance, mechanical response and thermal stability of the new high modulus asphalt materials were analysed through basic physical indicator tests, dynamic shear rheometer tests, thermogravimetric analysis (TGA), the time-temperature superposition principle, the Refutas model, and the Christensen-Andersen-Marasteanu model. The optimal results demonstrate that the optimal blend ratio of the developed asphalt is 12% EME/8% SBS/1.5% ZnO. Under this composition, the road performance indicator values of softening point, penetration and ductility of the modified asphalt met the standard requirements. The dynamic shear rheometer tests demonstrates that the inclusion of SBS and nano ZnO considerably enhanced the shear resistance and recovery deformation capacity of EME, effectively improving the high-temperature deformation resistance of asphalt. Furthermore,the Refutas and the Christensen-Andersen-Marasteanu model fitting results showed that adding SBS and nano ZnO considerably improved the temperature sensitivity of the EME types high modulus modified asphalt and exhibiting low frequency sensitivity. Compared to PR Module-type high modulus modifier(PRM),TGA reveals that the maximum thermal weight loss of EME-SBS-ZnO decreased by 3.5441%, indicating better thermal stability and the major character of SBS,EME and asphalt is physical reaction. Moreover, EME-nano ZnO-SBS high modulus asphalt at 64 °C shows Jnr-diff = 9.5% and passes the "E" extreme traffic grade. Additionally, its cost is 4.67% lower than that of the PRM high modulus modified asphalt, presenting considerable economic benefits.

Evaluation on Preparation and Performance of a Low-Carbon Alkali-Activated Recycled Concrete under Different Cementitious Material Systems.

A green, low-carbon concrete is a top way to recycle waste in construction. This study uses industrial solid waste slag powder (S95) and fly ash (FA) as binders to completely replace cement. This study used recycled coarse aggregate (RCA) instead of natural coarse aggregate (NCA). This is to prepare alkali-activated recycled concrete (AARC) with different cementitious material systems. Alkali-activated concrete (AAC) mixtures are modified for strength and performance based on the mechanical qualities and durability of AARC. Also, the time-varying effects of the environment on AARC properties are explored. The results show that with the performance enhancement of RCA, the mechanical performance of AARC is significantly improved. As RCA's quality improves, so does AARC's compressive strength. At a cementitious material content of 550 kg/m3, AARC's 28d compressive strengths using I-, II-, and III-class RCA were reduced by 2.2%, 12.7%, and 21.8%, respectively. I-class AARC has characteristics similar to natural aggregate concrete (NAC) in terms of shrinkage, resistance to chloride penetration, carbonization, and frost resistance. AARC is a new type of green building material that uses industrial solid waste to prepare alkali-activated cementitious materials. It can effectively reduce the amount of cement and alleviate energy consumption. This is conducive to the reuse of resources, environmental protection, and sustainable development.

3D Bioprinting of Liquid High-Cell-Proportion Bioinks in Liquid Granular Bath.

Embedded 3D bioprinting techniques have emerged as a powerful method to fabricate 3D engineered constructs using low strength bioinks; however, there are challenges in simultaneously satisfying the requirements of high-cell-activity, high-cell-proportion, and low-viscosity bioinks. In particular, the printing capacity of embedded 3D bioprinting is limited as two main challenges: spreading and diffusion, especially for liquid, high-cell-activity bioinks that can facilitate high-cell-proportion. Here, a liquid-in-liquid 3D bioprinting (LL3DBP) strategy is developed, which used a liquid granular bath to prevent the spreading of liquid bioinks during 3D printing, and electrostatic interaction between the liquid bioinks and liquid granular baths is found to effectively prevent the diffusion of liquid bioinks. As an example, the printing of positively charged 5% w/v gelatin methacryloyl (GelMA) in a liquid granular bath prepared with negatively charged κ-carrageenan is proved to be achievable. By LL3DBP, printing capacity is greatly advanced and bioinks with over 90% v/v cell can be printed, and printed structures with high-cell-proportion exhibit excellent bioactivity.

Adjusting methylation levels with nucleus proportions highlights functional significance of differentially methylated cytosines associated with pre-eclampsia.

Studies on DNA methylation alterations associated with pre-eclampsia (PE) have improved our understanding of the mechanisms underlying this disorder. However, differentially methylated cytosines (DMCs) have not been adjusted for cell-type heterogeneity, hampering the identification of alterations that drive disease risk. Using a reference-based, cell-type deconvolution approach, we estimated the nuclear proportions of 335 placental samples based on DNA methylation data. We found that the nuclei of total trophoblast lineages accounted for more than 80% of the placental samples, with a significant increase in PE placentas. The nuclear proportions of stromal and Hofbauer cells decreased in PE placentas. Our nuclear proportion estimation reflected previous histological knowledge on the changes in cell type proportions in PE placentas. We corrected 2125 DMCs associated with early-onset PE for cell-type heterogeneity by adjusting for the nuclear proportions and observed a notable reduction in the association signals, with 145 probes not reaching epigenome-wide significance. After correction, the top 200 significant DMCs were strongly enriched in active enhancers in trophoblast lineages, whereas 145 non-significant probes were enriched in regions with a quiescent state of chromatin. Our results suggest that future epigenetic studies of PE should focus on functional regulatory sequences.

Predicting postoperative mechanical complications with the ethnicity-adjusted global alignment and proportion score in degenerative scoliosis: does paraspinal muscle degeneration matter?

BACKGROUND: The global alignment and proportion (GAP) score was developed to predict mechanical complications (MCs) after adult spinal deformity surgery but showed limited sensitivity in the Asian population. Considering variations in sagittal parameters among different ethnic groups, our team developed the ethnicity-adjusted GAP score according to the spinopelvic parameters of 566 asymptomatic Chinese volunteers (C-GAP score). Notably, degenerative scoliosis (DS) patients with MCs following corrective surgery have more severe paraspinal muscle degeneration. For DS patients with various sagittal alignments, the unevenly distributed degeneration of paraspinal muscle may exert different influences on MC occurrence and largely affect the accuracy of the C-GAP score in clinical assessment. Therefore, incorporating paraspinal muscle degeneration indices within the C-GAP score may improve its accuracy in predicting MC occurrence. PURPOSE: We aimed to clarify the influence of paraspinal muscle degeneration on the C-GAP score predicting MC occurrence following DS surgery and modify the C-GAP score with paraspinal muscle degeneration parameters. STUDY DESIGN: A retrospective case-control study. SAMPLE SIZE: 107 adult degenerative scoliosis patients. OUTCOME MEASURES: Demographic information, postoperative sagittal spinopelvic parameters, the GAP score, the C-GAP score, and paraspinal muscle degeneration parameters. METHODS: A total of 107 DS patients undergoing posterior spinal fusion surgery (≥4 vertebrae) with a minimum of 2 years follow-up (or experiencing MCs within 2 years) were retrospectively reviewed. Their C-GAP score was calculated based on our previous study and patients were divided into 3 C-GAP categories, "proportioned" (P), "moderately disproportioned" (MD), and "severely disproportioned" (SD). Relative cross-sectional area (cross-sectional area of muscle-disc ratio×100, rCSA) and fat infiltration rate, FI% at L1/2, L2/3, L3/4, and L4/5 discs were quantitatively evaluated using magnetic resonance imaging (MRI). In each C-GAP category, patients were additionally divided into the MC group and the non-MC group to analyze their paraspinal muscle degeneration. A multivariable logistic regression model consisting of the CSA-weighted average FI% (total FI%) and the C-GAP score, C-GAPM was constructed. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves was used to evaluate the predictability of the GAP score, the C-GAP score, FI%, and C-GAPM. This project was supported by the National Natural Science Foundation of China (No.82272545) and Special Fund of Science and Technology Plan of Jiangsu Province (No.BE2023658). RESULTS: For all 107 patients, FI% at L1/2, L2/3, L3/4, and L4/5 discs and the total FI% of the MC group (n=32) were significantly higher than those of the non-MC group (n=75). The MC rates of 3 original GAP categories, P, MD, and SD categories were 25.00% (6/24), 27.03%(10/37), and 34.78% (16/46) (χ2=0.944, p=0.624). Based on the C-GAP score, the MC rates of the P, MD, and SD categories were 11.90% (5/42), 34.69% (17/49), and 62.50% (10/16), showing significant differences (χ2=15.137, p=0.001). In the C-GAP MD category, compared with the non-MC group (n=32), the MC group (n=17) has a higher total FI% (26.16(22.95, 34.00) vs. 22.67(16.39, 27.37)), p=0.029). A similar trend was identified in the C-GAP SD category (34.79±11.56 vs. 19.00±5.17, p=0.007), but not in the C-GAP P category (25.09(22.82, 32.66) vs. 24.66(17.36, 28.63), p=0.361). The AUC of the GAP score, the C-GAP score, the total FI%, and C-GAPM were respectively 0.601, 0.722, 0.716, and 0.772. CONCLUSIONS: Paraspinal muscle degeneration exerts a significant effect on the occurrence of MC in the C-GAP MD, SD instead of P category. The integration of paraspinal muscle FI% with the C-GAP score (C-GAPM) enables a more accurate prediction of MCs following DS surgery. Surgeons should pay adequate attention to paraspinal muscle degeneration during surgical planning and postoperative management for patients in the C-GAP MD and SD categories.

Priapism Presentations in a Saudi Arabian Emergency Department: A Retrospective Study at a Tertiary Care Hospital.

OBJECTIVES: To examine the distribution, clinical characteristics, and management of priapism in a Saudi Arabian tertiary care setting to provide a regional perspective. SUBJECTS AND METHODS: This retrospective chart review included 29 male patients presenting with priapism at a tertiary care hospital in Riyadh, Saudi Arabia, from January 2011 to June 2023. Data were collected on patient demographics, clinical presentation, treatment modalities, and outcomes. RESULTS: The study found recurrent episodes of priapism in many patients, with a significant number associated with hematological diseases, notably sickle cell disease. Most treatments involved non-surgical methods. A notable finding was the correlation between the duration of priapism episodes and the likelihood of hospital admissions, suggesting that prolonged episodes often required more extensive medical attention. CONCLUSIONS: Priapism often presents as a chronic and recurrent condition requiring personalized management strategies. This study emphasizes the importance of recognizing regional occurrence patterns to enhance the management of priapism and suggests a need for further research in regions where this condition is less common.

Potential Predictor of Epigenetic Age Acceleration in Men: 2D:4D Finger Pattern.

OBJECTIVES: Second to fourth digit ratio is widely known indicator of prenatal sex hormones proportion. Higher prenatal androgenization results in longer fourth finger and lower 2D:4D index. The aim of this study was to determine whether the 2D:4D digit ratio is associated with DNA methylation (DNAm) age dependently on sex. MATERIAL AND METHODS: The study included 182 adults (106 females and 76 males) with a mean age of 51.5 ± 13 years. The investigation consisted of three main parts: a survey, anthropometric dimensions measurements (fingers length) and methylome analysis using collected blood samples. Genome-wide methylation was analyzed using EPIC microarray technology. Epigenetic age and epigenetic age acceleration were calculated using several widely applied algorithms. RESULTS: Males with the female left hand pattern had more accelerated epigenetic age than those with the male pattern as calculated with PhenoAge and DNAmTL clocks. CONCLUSIONS: Finger female pattern 2D:4D above or equal to 1 in males is associated with epigenetic age acceleration, indicating that prenatal exposure to estrogens in males may be related to aging process in the later ontogenesis.

Response and conflict expectations shape motor responses interactively.

Efficient responses in dynamic environments rely on a combination of readiness and flexibility, regulated by anticipatory and online response control mechanisms. The latter are required when a motor response needs to be reprogrammed or when flanker stimuli induce response conflict and they are crucially modulated by anticipatory signals such as response and conflict expectations. The mutual influence and interplay of these control processes remain to be elucidated. Our behavioral study employed a novel combined response cueing/conflict task designed to test for interactive effects of response reprogramming and conflict resolution and their modulation by expectations. To this end, valid and invalid response cues were combined with congruent and incongruent target flankers. Expectations were modulated by systematically manipulating the proportions of valid versus invalid cues and congruent versus incongruent flanker stimuli in different task blocks. Reaction time and accuracy were assessed in thirty-one healthy volunteers. The results revealed response reprogramming and conflict resolution interactions for both behavioral measures, modulated by response and conflict expectations. Accuracy decreased disproportionally when invalidly cued targets with incongruent flankers were least expected. These findings support coordinated and partially overlapping anticipatory and online response control mechanisms within motor-cognitive networks.

Enhance the Proportion of Fe3+ in NiFe-Layered Double Hydroxides by utilizing Citric Acid to Improve the Efficiency and Durability of the Oxygen Evolution Reaction.

NiFe-layered double hydroxides (NiFe-LDH) are a type of catalyst known for their exceptional catalytic performance during the oxygen evolution reaction (OER). In this study, citric acid was incorporated into the synthesis process of NiFe-LDH, resulting in the NiFe-LDH-CA catalyst with superior OER performance. The catalytic efficacy is evaluated using linear sweep voltammetry (LSV), which demonstrates a significant reduction in the OER overpotential from 320 mV to 240 mV at a current density of 100 mA cm-2. X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectrum (XAS) indicate that the distribution of nickel valence states showed no significant difference between two samples, yet the NiFe-LDH-CA has a significantly higher proportion of Fe3+ ions in its iron content. In-situ Raman spectroscopes reveal that Fe3+ broadens the redox potential of nickel and Pourbaix diagrams indicate that higher Fe3+ levels could facilitate the interaction with oxygen active sites. Based on the analysis of test data, we propose a hypothesis that the high proportion of Fe3+ in catalysts may accelerate the oxygen evolution process by modulating the redox potential of nickel and engaging with reactive oxygen species. This provides valuable insights into how to improve the reaction rate of nickel-based catalysts.

Spinal alignment and surgical correction in the aging spine and osteoporotic patient.

Background: The aging spine often presents multifaceted surgical challenges for the surgeon because it can directly and indirectly impact a patient's spinal alignment and quality of life. Elderly and osteoporotic patients are predisposed to progressive spinal deformities and potential neurologic compromise and surgical management can be difficult because these patients often present with greater frailty. Methods: This was a literature review of spinal alignment changes, preoperative considerations, and spinal alignment considerations for surgical strategies. Results: Many factors impact spinal alignment as we age including lumbar lordosis flexibility, hip flexion, deformity, and osteoporosis. Preoperative considerations are required to assess the patient's overall health, bone mineral density, and osteoporosis medications. Careful radiographic assessment of the spinopelvic parameters using various classification/scoring systems provide the surgeon with goals for surgical treatment. An individualized surgical strategy can be planned for the patient including extent of surgery, surgical approach, extent of the constructs, fixation techniques, vertebral augmentation, ligamentous augmentation, and staging surgery. Conclusions: Surgical treatment should only be considered after a thorough assessment of the patient's health, deformity, bone quality and corresponding age matched alignment goals. An individualized treatment approach is often required to tackle the deformity and minimize the risk of hardware related complications and pseudarthrosis. Anabolic agents offer a promising benefit in this patient population by directly addressing and improving their bone quality and mineral density preoperatively and postoperatively.

T lymphocyte proportion in Alzheimer's disease prognosis.

Bai et al investigate the predictive value of T lymphocyte proportion in Alzheimer's disease (AD) prognosis. Through a retrospective study involving 62 AD patients, they found that a decrease in T lymphocyte proportion correlated with a poorer prognosis, as indicated by higher modified Rankin scale scores. While the study highlights the potential of T lymphocyte proportion as a prognostic marker, it suggests the need for larger, multicenter studies to enhance generalizability and validity. Additionally, future research could use cognitive exams when evaluating prognosis and delve into immune mechanisms underlying AD progression. Despite limitations inherent in retrospective designs, Bai et al's work contributes to understanding the immune system's role in AD prognosis, paving the way for further exploration in this under-researched area.

Evaluation of CTLA-4 and PD-L1 Expression in Thyroid Carcinoma and Its Prognostic Significance.

Introduction Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-ligand 1 (PD-L1) have revolutionised treatment and improved outcomes in various malignancies. We aimed to evaluate CTLA-4 and PD-L1 immunoexpression in thyroid tumours and correlated them with clinicopathological parameters. Methods The study included 90 cases of thyroid malignancies comprising papillary thyroid carcinoma (PTC) (n = 64, 54.2%), follicular thyroid carcinoma (FTC) (n = 19, 16.1%), anaplastic thyroid carcinoma (ATC) (n = 3, 2.5%), and poorly differentiated carcinoma (n = 4, 3.4%), two cases (1.69%) of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) along with 26 cases (22%) of benign thyroid lesions. CTLA-4 (UMAB249) and PD-L1 (SP263) expression were assessed in all the cases of thyroid tumours. Results were compared with clinicopathologic parameters and overall survival. Results PD-L1 was positive in all three cases of anaplastic thyroid carcinoma (ATC), 33% (n = 21) cases of PTC, and 16% (n = 3) cases of FTC. PD-L1 positivity was significantly associated at tumour proportion score (TPS) ≥1% with lymphovascular invasion and age ≤40 years and at TPS ≥50% with tumour necrosis and N-stage. Immune proportion score (IPS) did not correlate with any clinicopathological parameters except for the N-stage. CTLA-4 was positive in six cases of PTC (1-5%); five showed lymph node involvement (p = 0.032). IPS was positive in 14 cases, and a significant association was seen with lymph node metastasis, lymphocytic infiltration, and lymphovascular invasion. Three cases of PTC showed co-expression for PD-L1 and CTLA-4 in tumour cells. No significant association was seen between PD-L1 expression and survival. Conclusion The current data suggest that PD-L1 is expressed in differentiated thyroid carcinoma, mainly PTC and ATC, indicating higher responsiveness to immunotherapy. A subset of PTC showed co-expression of PD-L1 and CTLA-4. These findings suggest the need for further investigation to utilise combinational immunotherapy, including anti-PD-L1 and anti-CTLA-4.

The mediating role of metabolites between gut microbiome and Hirschsprung disease: a bidirectional two-step Mendelian randomization study.

Background: Gut microbiome (GM) was observed to be associated with the incidence of Hirschsprung disease (HD). However, the effect and mechanism of GM in HD is still unclear. To investigate the relationship between GM and HD and the effect of metabolites as mediators, a bidirectional two-step Mendelian randomization (MR) study was conducted. Methods: The study selected instrument variables (IVs) from summary-level genome-wide association studies (GWAS). The MiBioGen consortium provided the GWAS data for GM, while the GWAS data for metabolites and HD were obtained from the GWAS Catalog consortium. Two-sample MR analyses were performed to estimate bidirectional correlations between IVs associated with GM and HD. Then, genetic variants related to 1,400 metabolite traits were selected for further mediation analyses using the Product method. Results: This study found that seven genus bacteria had a significant causal relationship with the incidence of HD but not vice versa. 27 metabolite traits were significantly correlated with HD. After combining the significant results, three significant GM-metabolites-HD lines have been identified. In the Peptococcus-Stearoyl sphingomyelin (d18:1/18:0)-HD line, the Stearoyl sphingomyelin (d18:1/18:0) levels showed a mediation proportion of 14.5%, while in the Peptococcus-lysine-HD line, the lysine levels had a mediation proportion of 12.9%. Additionally, in the Roseburia-X-21733-HD line, the X-21733 levels played a mediation proportion of 23.5%. Conclusion: Our MR study indicates a protective effect of Peptococcus on HD risk that is partially mediated through serum levels of stearoyl sphingomyelin (d18:1/18:0) and lysine, and a risk effect of Roseburia on HD that is partially mediated by X-21733 levels. These findings could serve as novel biomarkers and therapeutic targets for HD.

An assessment of compositional methods for the analysis of DNA methylation-based deconvolution estimates.

DNA methylation (DNAm)-based deconvolution estimates contain relative data, forming a composition, that standard methods (testing directly on cell proportions) are ill-suited to handle. In this study we examined the performance of an alternative method, analysis of compositions of microbiomes (ANCOM), for the analysis of DNAm-based deconvolution estimates. We performed two different simulation studies comparing ANCOM to a standard approach (two sample t-test performed directly on cell proportions) and analyzed a real-world data from the Women's Health Initiative to evaluate the applicability of ANCOM to DNAm-based deconvolution estimates. Our findings indicate that ANCOM can effectively account for the compositional nature of DNAm-based deconvolution estimates. ANCOM adequately controls the false discovery rate while maintaining statistical power comparable to that of standard methods.

DNA methylation (DNAm)-based deconvolution provides highly accurate estimates of the proportion of each cell type in a mixed-cell type biological sample (e.g., whole-blood). These estimates can be used for examining the association between cell type proportions and biological or clinical end points; for example, comparing the estimated neutrophil proportion in whole blood between smokers and non-smokers. Cell proportion data has unique features which present challenges for traditional and widely used statistical methods. In response to this issue, our work presents two simulation studies and a real-world analysis that benchmark the performance of current standard statistical methods against an alternative method called analysis composition of microbes (ANCOM), which was originally developed for the analysis of microbiome data. In our real-world analysis we used DNAm data collected from Women's Health Initiative Long Life Study I and compared the results of each method against a gold-standard that is typically not available for these analyses. In each of our simulation studies, ANCOM was able to detect true differences in cell proportions between the groups being compared but had a much lower rate of false discovery compared with the standard statistical methods. Our real-world analysis demonstrated similar findings. Overall, our study highlights the potential of ANCOM as a powerful and robust method for analyzing DNAm-derived deconvolution estimates when the interest is comparisons of cell type proportions and biological or clinical end points. ANCOM's ability to minimize false discovery while maintaining robust statistical power positions it as a valuable addition to the epigenomic analysis toolkit.

Simulation analyses of the evolution of intra-inflorescence flowering patterns assuming selection on anthesis interval among individual flowers.

What conditions select flowering patterns within inflorescences, or variation in the anthesis interval within inflorescences among plants? Under what conditions are gradual blooming and simultaneous blooming, both traits related to floral display size, advantageous? We constructed a simulation model in which the opening times and longevities of individual flowers within inflorescences, the sizes of attractive structures of individual flowers, and the numbers of ovules and pollen grains produced by individual flowers evolve. Individual plants in the population compete for pollinators, and plants are selected by pollinators according to their floral display sizes and amounts of resources allocated to attractive structures. We found that, if the proportion of pollen on a pollinator deposited on a stigma was low, gradual blooming did not evolve even if inbreeding depression was greater than 0.5. This is because the amount of outcross-pollen on pollinators decreased at a low rate during flower visits within a single inflorescence, and the selfing rate was suppressed to a low level even if the floral display size was large. On the other hand, if the proportion of pollen deposition was high, gradual blooming evolved even if inbreeding depression was smaller than 0.5. This may be because gradual blooming can enhance pollen delivery to other plants by reducing the loss of self-pollen by geitonogamy. On the other hand, allocation ratios among floral organs (female and male organs and attractive structures) were independent of the degree of simultaneous and gradual blooming within inflorescences. We concluded that the evolution of gradual blooming is more strongly affected by the proportion of pollen on a pollinator deposited on a stigma than by inbreeding depression.

Frequency of antimicrobial-resistant bloodstream infections in 111 hospitals in Thailand, 2022.

OBJECTIVES: To evaluate the frequency of antimicrobial-resistant bloodstream infections (AMR BSI) in Thailand. METHODS: We analyzed data from 2022, generated by 111 public hospitals in health regions 1 to 12, using the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS), and submitted to the Ministry of Public Health, Thailand. Multilevel Poisson regression models were used. RESULTS: The most common cause of community-origin AMR BSI was third-generation cephalosporin-resistant Escherichia coli (3GCREC, 65.6%; 5101/7773 patients) and of hospital-origin AMR BSI was carbapenem-resistant Acinetobacter baumannii (CRAB, 51.2%, 4968/9747 patients). The percentage of patients tested for BSI was negatively associated with the frequency of community-origin 3GCREC BSI and hospital-origin CRAB BSI (per 100,000 tested patients). Hospitals in health regions 4 (lower central region) had the highest frequency of community-origin 3GCREC BSI (adjusted incidence rate ratio, 2.06; 95% confidence interval: 1.52-2.97). Health regions were not associated with the frequency of hospital-origin CRAB BSI, and between-hospital variation was high, even adjusting for hospital level and size. CONCLUSION: The high between-hospital variation of hospital-origin CRAB BSI suggests the importance of hospital-specific factors. Our approach and findings highlight health regions and hospitals where actions against AMR infection, including antimicrobial stewardship and infection control, should be prioritized.