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Integrated 3D imaging of FFPE lung tissue combining microCT, light and electron microscopy allows for contextualized ultrastructural and histological analysis
Abstract Classical histopathology of formalin fixed and paraffin embedded (FFPE) tissue using light microscopy (LM) remains the undisputed gold standard in biomedical microstructural lung tissue analysis. To extend this method, we developed an integrative imaging and processing pipeline which adds 3D context and screening capabilities by microCT (µCT) imaging of the entire paraffin block and adds ultrastructural information by correlative same-slide scanning electron microscopy (SEM). The different modalities are integrated by elastic registration to provide hybrid image datasets. Without compromising standard light microscopic readout, we overcome the limitations of conventional histology by combining and integrating several imaging modalities. The biochemical information contained in histological and immunohistological tissue staining is embedded into the 3D tissue configuration and is amplified by adding ultrastructural visualization of features of interest. By combining µCT and conventional histological processing, specimens can be screened, and specifically preselected areas of interest can be targeted in the subsequent sectioning process. While most of the µCT data shown in the manuscript was acquired at a Synchrotron, we further demonstrate that our workflow can also be applied using X-ray microscopy.
A surgical recovery matrix to evaluate post-surgical recovery in mice using sham and myocardial infarction models of cardiac surgery as prototypes
Examinations of biomarkers are useful in measuring overall health. Endpoints are critical to assess the threshold where the scientific aim of the study does not prevail over the wellbeing of experimental laboratory animal. However, parameters able to assess health and recovery after an acute post-surgical intervention are needed. To fill this gap, we combined a suite of qualitative and quantitative measurements and created a surgical recovery matrix (SRM) able to monitor and score rodent health and wellbeing after surgery. We established baseline values in healthy male and female retired breeder C57BL/6N mice as a control, no surgery (NoSx) cohort. To test if SRM scoring was useful in the immediate surgical period, we monitored changes in 18 parameters after sham (SH) and myocardial infarction (MI)-inducing surgeries over 3 days of recovery. The surgical manipulations and cardiac damage involved in MI-inducing surgery render its categorization as a major surgery. In contrast, SH surgery represents a minor surgery such that the surgical manipulations are identical to that of the MI surgery but without any manipulation/damage to the heart. Six hours after surgery, males and females showed deficits in nestlet integration, eye grooming, a hunched posture and rough coat appearance whereas greater body weight losses and impaired wound healing were recorded later in the observation period. Sex-specific differences were observed such that males showed a propensity to reduced mobility and lower surface body temperature whereas females had a reduced Body Condition Score. These parameters discriminated the very low scores detected in controls from the intermediate scores after SH surgery and the highest scores in mice severely debilitated by MI surgery. Further, we identified sex-specific and time-dependent changes such that the highest scores were detected in male mice after an MI versus SH surgery. We conclude that a combination of quantitative and qualitative parameters successfully evaluated mouse recovery and health after minor and major surgery.
Comparative analysis of physical, morphological, tensile and thermal stability characteristics of raw and alkali treated novel Tinospora cordifolia natural fiber
Abstract This research paper presents comparative analysis of morphological, physical, tensile and thermal properties of raw and NaOH treated natural fiber extracted from the stems of Tinospora cordifolia herbaceous vine. Diameter & density measurements, X-ray Diffraction (XRD) analysis, Scanning Electron Microscopy (SEM), Fourier Transform Infrared (FTIR) spectroscopy, single fiber tensile tests and Thermogravimetric analysis (TGA) were carried out. The diameter reduced and density increased post treatment. SEM images revealed the removal of non-cellulosic contents, finer fibrillation, more clear hexagonal structure and formation of pores & voids post treatment. The Crystalline Index (C.I) and Crystallite Size (C.S) obtained from the XRD spectra enhanced after treatment which is evident from the absence of amorphous shoulders/bumps. FTIR analysis have revealed the removal of constituents such as hemicellulose, lignin and wax. The tensile strength enhanced, Young’s modulus and percent elongation at break reduced post treatment. The thermal stability enhanced; however, the maximum degradation showed a slight reduction.
Effect of inverted visual acceleration profile on vestibular heading perception
Visual motion is ambiguous in that it can either represent object motion or self-motion. Visual-vestibular integration is most advantageous during self-motion. The current experiment tests the hypothesis that the visual motion needs to have a motion profile consistent with the inertial motion. To test this, we examined the effect on heading perception when the visual stimulus was consistent with the inertial motion compared to an inverted visual stimulus, which was thus inconsistent with inertial motion. Twenty healthy human subjects (mean age 20 ± 3 years, 13 female) experienced 2s of translation, which they reported as left or right. A synchronized 2s visual heading was offset by 0°, ± 45°, ± 60°, or ±75°. In randomly interleaved trials, the visual motion was consistent with the inertial motion or inverted – it started at the peak velocity, decreased to zero mid-stimulus, and then accelerated back to the peak velocity at the end. When the velocity profile of the visual stimulus matched the velocity profile of inertial motion, the inertial stimulus was biased 10.0 ± 1.8° (mean ± SE) with a 45° visual offset, 8.9 ± 1.7° with a 60° offset, and 9.3° ± 2.5 ± with a 75° offset. When the visual stimulus was inverted so it was inconsistent with the inertial motion, the respective biases were 6.5 ± 1.5°, 5.6 ± 1.7°, and 5.9 ± 2.0°. The biases with the inverted stimulus were significantly smaller (p < 0.0001), demonstrating that the visual motion profile is considered in multisensory integration rather than simple trajectory endpoints.
MicroRNA signature predicts post operative atrial fibrillation after coronary artery bypass grafting
Integrative analysis of epigenetic subtypes in acute myeloid Leukemia: A multi-center study combining machine learning for prognostic and therapeutic insights
Background Acute Myeloid Leukemia (AML) exhibits significant heterogeneity in clinical outcomes, yet current prognostic stratification systems based on genetic alterations alone cannot fully capture this complexity. This study aimed to develop an integrated epigenetic-based classification system and evaluate its prognostic value. Methods We performed multi-omics analysis on five independent cohorts totaling 1,103 AML patients. The Cancer Genome Atlas-Acute Myeloid Leukemia (TCGA-LAML) cohort (n = 83) provided comprehensive multi-omics data including DNA methylation profiles (Illumina 450K platform), RNA sequencing (mRNA, lncRNA, and miRNA), and somatic mutation profiles. The BEAT (n = 649), TARGET (n = 156), GSE12417 (n = 79), and GSE37642 (n = 136) cohorts contributed transcriptome data. Molecular subtypes were identified using empirical Bayes-based clustering on the TCGA cohort. LSC17 scores were calculated using a validated 17-gene expression signature. A random survival forest model was developed integrating molecular features with LSC17 scores, validated across all cohorts. Immune microenvironment analysis employed multiple deconvolution methods (ESTIMATE, CIBERSORT, xCell) and pathway analysis (GSVA, GSEA). Drug sensitivity was predicted using the pRRophetic algorithm with GDSC database reference. Results Multi-omics integration revealed two molecularly distinct AML subtypes with significant survival differences (CS2 vs CS1, P < 0.001). The random survival forest model, incorporating 20 key epigenetic features (including CPNE8, CD109, and CHRDL1) and LSC17 scores, achieved superior prognostic accuracy (C-index: 0.72–0.78) across validation cohorts. Both epigenetic risk score (HR = 2.45, 95%CI: 1.86–3.24) and LSC17 score (HR = 1.89, 95%CI: 1.42–2.51) maintained independent prognostic value in multivariate analysis. Integration of both scores in a nomogram improved 1-, 3-, and 5-year survival predictions (C-index: 0.81). High-risk patients exhibited distinct immune profiles with elevated M2 macrophages (1.8-fold) and Tregs (2.3-fold), while low-risk patients showed enhanced NK cell activity (2.1-fold). Drug sensitivity analysis identified differential responses to epigenetic regulators (LAQ824, P = 0.000139; MS-275, P = 0.00104) and proteasome inhibitors (Bortezomib, P = 0.00747; MG-132, P = 0.0106) between risk groups. Conclusions This integrated classification system combining epigenetic features and stem cell signatures provides new insights into AML heterogeneity and therapeutic targeting. The complementary nature of epigenetic and stem cell-related prognostic factors suggests potential for improved risk stratification in clinical practice. Future prospective validation studies are warranted to confirm these findings.
Improving ACS prediction in T2DM patients by addressing false records in electronic medical records using propensity score
Advanced predictive modeling for enhanced mortality prediction in ICU stroke patients using clinical data
Background Stroke is second-leading cause of disability and death among adults. Approximately 17 million people suffer from a stroke annually, with about 85% being ischemic strokes. Predicting mortality of ischemic stroke patients in intensive care unit (ICU) is crucial for optimizing treatment strategies, allocating resources, and improving survival rates. Methods We acquired data on ICU ischemic stroke patients from MIMIC-IV database, including diagnoses, vital signs, laboratory tests, medications, procedures, treatments, and clinical notes. Stroke patients were randomly divided into training (70%, n=2441), test (15%, n=523), and validation (15%, n=523) sets. To address data imbalances, we applied Synthetic Minority Over-sampling Technique (SMOTE). We selected 30 features for model development, significantly reducing feature number from 1095 used in the best study. We developed a deep learning model to assess mortality risk and implemented several baseline machine learning models for comparison. Results XGB-DL model, combining XGBoost for feature selection and deep learning, effectively minimized false positives. Model’s AUROC improved from 0.865 (95% CI: 0.821 - 0.905) on first day to 0.903 (95% CI: 0.868 - 0.936) by fourth day using data from 3,646 ICU mortality patients in the MIMIC-IV database with 0.945 AUROC (95% CI: 0.944-0.947) during training. Although other ML models also performed well in terms of AUROC, we chose Deep Learning for its higher specificity. Conclusion Through enhanced feature selection and data cleaning, proposed model demonstrates a 13% AUROC improvement compared to existing models while reducing feature number from 1095 in previous studies to 30.
0.46 Terahertz wave irradiation inhibit transcription reaction in liposomes
Abstract Terahertz waves are absorbed by hydrogen bonds between water molecules and proteins, and low-frequency terahertz waves, in particular, have been reported to cause changes in protein function and inhibit cell division. In this study, we established an experimental system to irradiate liposomes containing T7 RNA polymerase for in vitro transcription reactions with terahertz waves in the absence of external fluid, and analyzed the resulting changes in transcription reaction efficiency. Terahertz wave irradiation at 460 GHz did not alter the shape of the liposomes, but the intraliposomal transcription reaction was non-thermally inhibited during irradiation, regardless of the energy per pulse. After irradiation, the transcription reaction efficiency was found to be higher than in non-irradiated samples. Since our experimental system allows for the analysis of a wide range of terahertz wave frequencies, pulse widths, pulse intervals, and energy levels, we can comprehensively explore the effects of terahertz waves on living organisms, an area that has been challenging to study in the past. This capability significantly broadens the potential applications of terahertz waves in future research.
Exploring the critical waste factors affecting highway construction projects in Pakistan
Highway construction projects are known for their propensity to consume enormous quantities of materials and their susceptibility to generate considerable waste. Adequate research has been conducted on identifying the causes of waste produced in building projects, however, there are limited studies available on identifying causative factors for highway projects. This study aims to identify and evaluate the causes and factors of waste generated on highway projects using a literature review and questionnaire survey technique. Causes leading to waste in highway projects were identified from the literature as well as from highway construction experts. Subsequently, quantitative data were collected from 127 highway construction professionals using a Likert Scale questionnaire survey, which was ranked using the Relative Importance Index (RII) and further analyzed by using a very robust Factor Analysis (FA) technique. RII results highlight the most significant causes of waste in highway construction, while FA suggests the main factors contributing to the waste in highway projects. The top five most significant causes of waste revealed by this study were: (1) mistakes of surveyors, (2) faulty drawings, (3) incompetence of quantity surveyors, (4) faulty/substandard work, and (5) poor workers’ skills, whereas the seven waste factor groups evaluated by the study were: (1) design, (2) storage, (3) survey, (4) workers, (5) waste management, (6) site management, and (7) external. This study further suggested waste management and mitigation strategies for highway construction projects corresponding to each factor group. This is a novel study on waste generation in highway projects in Pakistan and will assist academia and industry practitioners in understanding and controlling construction waste generation in highway projects during various stages of project execution.
Knowledge, attitude and practice of rehabilitation management of the caregivers of pediatric patients with hemiplegia
Quantum Coulombic Interactions Mediate Free Radical Control in Radical SAM Viperin/RSAD2
Behind the white coat: Unraveling the patterns of workplace violence in an Italian healthcare setting – An epidemiological exploration
Aim In the present study, we aimed to provide an epidemiological and descriptive overview of violence against healthcare workers in an Italian university hospital, presenting and characterizing the risk factors in the department where such events occur and to propose ways to prevent aggressive behaviors. Methods We retrospectively analyzed violence against healthcare workers by patients and attendants at an Italian university hospital from 2020 to 2022. Aggressions were documented in anonymous incident reports collected by the hospital’s Clinical Risk Unit. The frequencies and percentages were calculated via a descriptive analysis. Chi-square tests were used to compare the wards with the most aggressions to other wards. Results Of the 219 included cases, the aggressors were primarily male patients and the victims female nurses. Most of the aggressions occurred in the psychiatry and emergency department. Among the aggressors, 41.1%, had a psychiatric diagnosis or neurocognitive impairment. Over half the cases involved physical aggression. Compared to other wards, psychiatric wards showed an even distribution of aggressor gender, a higher proportion of male victims, fewer verbal aggressions, and less impact from environmental factors. Notably, female aggressor status (p < 0.001, OR = 8.687) and involvement in physical assaults (p < 0.001, OR = 15.236) were identified as independent risk factors associated with aggression in psychiatric settings. Conclusion Our findings align with the literature in that most of the incidents occurred in the psychiatry and emergency medicine departments and involved nurses. However, physical rather than verbal aggression predominated. Notable distribution, risk factor, and qualitative differences were observed between the psychiatric and non-psychiatric services, which warrants further investigation. Our results could be useful in implementing better prevention strategies based on the type of ward.
A robust chronic obstructive pulmonary disease classification model using dragonfly optimized kernel extreme learning machine
Correction: A novel implantable mechanism-based tendon transfer surgery for adult acquired flatfoot deformity: Evaluating feasibility in biomechanical simulation
Correction: The role of vesicle trafficking genes in osteoblast differentiation and function
Essential oil-derived compounds target core fatigue-related genes: A network pharmacology and molecular Docking approach
Fatigue is a widespread condition associated with various health issues, yet identifying specific bioactive compounds for its management remains challenging. This study integrates network pharmacology and molecular docking to uncover essential oil-derived compounds with potential antifatigue properties by targeting key genes and molecular pathways. A comprehensive analysis of 872 essential oil compounds was conducted using PubChem, with target prediction via SwissTargetPrediction. The protein-protein interaction (PPI) network and KEGG pathway analysis identified core fatigue-related targets, including ALB, BCL2, EGFR, IL-6, and STAT3, in metabolic dysregulation and inflammatory responses linked to fatigue. Molecular docking exhibits strong binding affinity between key compounds such as Calamenene, T-cadinol, and Bornyl acetate and core targets, suggesting their potential antifatigue effects. However, ADMET analysis confirmed T-cadinol’s drug-likeness, suggesting good bioavailability and minimal toxicity risks. Thus, molecular docking revealed high binding affinity, which was further validated through a 100 ns MD simulation and demonstrated stable interactions with low root mean square deviation (RMSD). Additionally, hydrogen bond analysis confirmed that T-cadinol maintained consistent interactions with key residues such as Thr-790 in EGFR, Arg-222 in ALB, and Arg-104 in IL-6, indicating strong binding stability. While this study provides valuable computational insights, further in vitro and in vivo validation is necessary to confirm these findings and explore potential therapeutic applications.
Performance of Doppler ultrasound parameters for the detection of stenosis in distal arteriovenous fistulas
Study protocol: The effect of a low-carbohydrate enteral nutrition formula on postoperative hyperglycemia in non-diabetic patients with esophageal cancer: A randomized exploratory phase II trial (ENLICHE study)
Background Postoperative hyperglycemia in diabetic patients is a widely known risk factor for postoperative infectious complications (PICs) after esophagectomy; however, the significance of glycemic control in non-diabetic patients is less clear. In diabetic patients, early postoperative management of esophagectomy favors low-carbohydrate enteral nutrition (EN) over standard EN to suppress the risk of glycemic spike. Our single-center, randomized phase II trial seeks to test the hypothesis that low-carbohydrate EN can suppress hyperglycemia in non-diabetic patients who undergo esophagectomy. Herewith we present the study protocol. Methods A total of 50 patients will be enrolled and randomly assigned (1:1 ratio) to standard or low-carbohydrate EN. Randomization will be stratified by operation time (≥560 vs. < 560 min) and HbA1c (6.0–6.4% vs. < 6.0%). Both EN formula will be fed according to the following protocol: 400 mL/24 h on postoperative day (POD)-1; 800 mL on POD-2; 1200 mL on POD-3 and 1600 mL from POD-4 to POD-8. On POD-9, oral food intake will be initiated. A continuous glucose monitoring (CGM) device will be used to monitor blood glucose levels from POD-1 to −8. The primary outcome is the mean time-in-range (TIR) across the 48 h from POD-1 to −2. TIR is defined as the percentage-time that blood glucose remains within the targeted range of 70−180 mg/dL. The primary analysis will calculate the least squares mean difference in TIR over the 48 h (POD-1 to −2) between the two groups, with p-values calculated to test the null hypothesis that the mean difference between the groups is zero. The secondary outcomes will be as follows: 1) the incidence of PICs and/or other adverse events within 30 days after esophagectomy or during the hospital stay; 2) the number of cases requiring any dose alteration in EN formula during monitoring; 3) the number of cases requiring interventions for hyperglycemia or hypoglycemia; 4) the rates in change of nutritional indicators, such as serum albumin, prealbumin, and total protein levels, during the post-surgical hospital stay (vs. those values on the day of admission); and 5) the following CGM indices in relation to the incidence rate of PICs within 30 days after esophagectomy: the mean values for time-above-range (TAR), area under the curve (AUC), and TIR for each POD or from POD-1 to −8. TAR is defined as the percentage of time of a patient is recorded as having hyperglycemia (>blood glucose level of 180 mg/dL), and is indicative of the frequency and duration of hyperglycemia. AUC, which identifies periods of hyperglycemia and provides a comprehensive picture of glucose variability and control in diabetes management, is defined as the area under the curve over blood glucose level of 180 mg/dL on CGM monitoring. Discussion This study is the first to investigate the impact of a low-carbohydrate EN formula on hyperglycemic control during perioperative nutritional management of esophageal cancer. These results will help to outline whether glycemic control should be also considered for non-diabetic patients during hospital care. Trial registration This trial has been registered in the Japanese Registry of Clinical Trials (jRCTs031240081).