This study investigates the microstructural effects, energy evolution, and damage progression of sandstone under uniaxial cyclic freeze-thaw (F-T) conditions. Using the roof sandstone from Shuangma No. 1 Mine, uniaxial compression tests were performed on samples subjected to varying numbers of F-T cycles. PFC3D simulations were employed to reproduce the failure process and analyze microcrack evolution.Results show that both the compressive strength and elastic modulus of sandstone decrease with increasing F-T cycles. When loaded perpendicular to the freeze-thaw direction, the elastic modulus of sandstone is significantly higher than that under parallel loading; conversely, the peak strain and compressive strength show the opposite trend. Post-failure analysis reveals an increase in the total number of cracks, tensile cracks, and shear cracks with more F-T cycles for both loading directions. However, the total and tensile crack counts in the parallel direction remain consistently higher than in the perpendicular direction.Energy analysis indicates that the proportion of elastic energy at peak stress continuously decreases with more F-T cycles, though it remains higher in the parallel direction. A rebound occurs at 140 cycles. The cumulative elastic energy ratio also decreases with increasing cycles, with the parallel direction consistently exhibiting higher values. Damage evolution equations, derived from the principle of minimum energy dissipation, show that the damage threshold in the parallel direction continuously increases and stays higher than in the perpendicular direction, where it first decreases and then increases. Final damage values in both directions initially rise and then decline, with transition points at 140 and 110 cycles, respectively. These findings provide theoretical guidance for rock engineering in cold regions.
This study investigated the effects of supplementing milk with fermented black garlic (G) and Hypericum scabrum decoction (H) on growth performance, immune status, diarrhea incidence, inflammatory responses, oxidative stress, and gut microbiota in 28 pre-weaning Holstein calves. Blood WBC counts were significantly higher in the control (C) group than in the treatment groups (P = 0.007). At 45 days of age, CAT activity was significantly higher in the C group as compared to experimental calves. Concentration of IL-6 was significantly lower in the treatment groups (P < 0.01). Regarding gut health, fecal scores significantly improved in supplemented groups, particularly on day 45 (P < 0.05), and fecal E. coli counts were reduced by 10.7% in the GH group (P = 0.043). Serum IgA was significantly higher in the GH group (P = 0.044), suggesting a more robust first-line immune defense. However, a selective antimicrobial effect was observed, as bifidobactera levels also decreased by 9.8% and 8.7% in G and in GH groups as compared to C (P = 0.024). No significant differences were observed between groups in live weight and body measurements throughout the experimental period, except for in heart girth on day 60 (P < 0.05). Starter consumption did not differ between groups, furthermore, the C group had higher FCR and group H had higher ADG than the C group during the 0-60-day period, and no difference was observed in FCR and ADG during other periods In conclusion, while fermented black garlic and H. scabrum support gastrointestinal health and modulate inflammatory responses, their impact on overall growth performance remains limited under the studied conditions, and the reduction in beneficial bifidobacterium warrants careful long-term evaluation.
Patients with clinically advanced node-positive (cN2/3), non-metastatic breast cancer have traditionally undergone axillary lymph node dissection (ALND) after neoadjuvant systemic therapy (NST). Randomized de-escalation trials have excluded cN2/3 disease. However, some of these patients achieve nodal pathologic complete response (ypN0), suggesting potential for less extensive axillary surgery. We aimed to determine ypN0 rates and identify factors associated with nodal response. The National Cancer Database (NCDB, 2004-2022) was analyzed. Female patients with cN2/3, non-metastatic breast cancer who received neoadjuvant chemotherapy (NAC) followed by surgery were included. Patients were stratified by pathologic nodal status. Clinicopathologic variables were compared, and multivariable logistic regression identified factors associated with pathologic complete response (pCR). Overall survival was analyzed using Kaplan-Meier methods. Among approximately 4 million patients with breast cancer, 20,402 met the inclusion criteria. Of these, 36.9% (n = 7526) achieved ypN0 and 63.1% (n = 12,876) had residual nodal disease. ypN0 was associated with younger age (52 vs 54 years), higher Ki-67 (67% vs 42%), and higher tumor grade (37% vs 21% vs 11% for grades 3, 2, and 1, respectively; p < 0.001). Higher ypN0 rates were observed in human epidermal growth factor receptor 2-positive (70%), hormone receptor-negative (62%), and triple-negative tumors (57%), whereas hormone receptor-positive tumors had lower ypN0 rates (29%). Overall, pCR occurred in 22.6%. Despite this, 60.8% underwent ALND. Multivariable analysis showed that higher Ki-67 (odds ratio [OR] 1.29), younger age (OR 0.99 per year), and hormone receptor-negative status (OR 0.24) were associated with pCR (p < 0.001). pCR and ypN0 were associated with improved OS (hazard ratio 0.31 and 0.39, respectively; p < 0.001). Over one-third of patients achieved ypN0 after NST. These findings highlight an opportunity to refine axillary management in selected cN2/3 patients.
As an increasing number of states legalize recreational cannabis, it is increasingly important to understand the optimal tax design for recreational cannabis. Currently, various tax bases (weight, potency, price) and rates are used. However, the empirical evidence on the impact of tax-related attributes (pre-tax prices, tetrahydrocannabinol [THC] levels, tax bases, and tax rates) and their interactions on consumption is limited. To address this evidence gap, this study utilizes a split-sample volumetric choice experiment to understand the impact of pre-tax prices, tax bases, tax rates, and THC levels on cannabis consumption and THC intake by US adult users. We further estimated the own- and cross-price elasticities for four cannabis forms (legal flower, illegal flower, edibles, and vaping concentrates). We collected a nationally representative sample of N = 1525 US adults aged 21+ who reported the past 30-day use of recreational cannabis in June and July 2024. Participants were randomized into seeing one of the three different tax bases, and each person answered 9 choice questions where they were given varying combinations of pre-tax prices, tax rates, and THC levels of the four cannabis products. Zero-inflated negative binomial regressions were used to estimate the impacts of varying factors on the cannabis consumption (units and THC) and own- and cross-price elasticities. The interactions between tax bases and their targeted attributes were explored using a linear model accounting for individual fixed effects. Higher pre-tax prices and tax rates significantly reduce consumption, whereas higher THC levels increase consumption. Compared to a tax rate of 60% of pretax prices or equivalent, an 80% rate does not induce further consumption reduction. The overall price elasticities of cannabis demand range from -0.4 to -0.5, with form- or product-specific price elasticities ranging between -0.2 and -0.4. Illegal and legal flowers are substitutes for each other. Edibles and cartridges are complements for each other. In addition, illegal flowers are substitutes for legal cartridges, and edibles are complements to flowers. While increases in the prices of legal products significantly reduce their consumption, 89% of this reduction may be offset by switching to illegal products. While tax bases do not significantly impact consumption, a potency tax base reduces the consumption of higher potency products, and a price tax base reduces the consumption of higher-priced products. If the illegal market is restricted, policymakers can expect increasing cannabis prices using excise taxes to reduce both unit and THC consumption, while generating tax revenues. However, given the sizable illegal market, a large portion of the consumption reduction due to taxes may be offset by switching to illegal products. Tax rates reduce consumption in addition to base prices. There is room to increase cannabis tax rates to 60% of pretax prices or equivalent to counter the decreasing prices. While tax bases are not effective in reducing overall consumption, they can shift the preference of products with the attributes that they target (e.g., high potency or high price); therefore, they could be a useful tool to shift product choices. Capping THC levels also has a direct impact on reducing consumption.
Patients with axial spondyloarthritis (AxSpA) with difficult-to-manage (D2M) or treatment-refractory (TR) disease represent an unmet clinical need, but real-world data remain limited. To determine the frequency, demographic, clinical, and psychosocial characteristics of D2M and TR AxSpA patients in a real-world setting, we analyzed data from the Greek AxSpA Registry. D2M disease was defined as Ankylosing Spondylitis Disease Activity Score [ASDAS] ≥ 2.1 despite failure of ≥ 2 biologic (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) with different mechanisms of action. TR was defined as D2M status plus C-reactive protein (CRP) ≥ 0.5 mg/dL after exclusion of infectious causes. D2M, TR, and non-D2M groups were compared and factors associated with D2M status were explored using multivariable regression analysis. Among 395 patients with AxSpA, 40 (10.1%) patients were classified as D2M and 22 (5.6%) as TR. In univariable analysis, higher BASDAI at diagnosis, extra-spinal manifestations (arthritis, dactylitis, enthesitis and psoriasis), BMI ≥ 25 kg/m², current smoking, depression, number of comorbidities, as well as unemployment were associated with the D2M status. In multivariable analysis, unemployment (OR 6.08, 95% CI 1.90-19.46), BASDAI at diagnosis (OR 1.62, 95% CI 1.17-2.24), and depression (OR 2.97, 95% CI 1.04-8.50) remained independently associated with D2M status. Patients with TR AxSpA were characterized by higher BASDAI at diagnosis, more syndesmophytes, and multiple comorbidities. D2M AxSpA is characterized by a more aggressive disease from the outset and throughout, a higher frequency of comorbidities, particularly depression, and an independent association with unemployment. These findings support multidisciplinary management targeting inflammatory burden, modifiable lifestyle factors and psychosocial vulnerability.
Non-viral vectors have garnered considerable attention due to their biosafety and low immunotoxicity. However, non-viral gene transfection has been limited in applicability due to low effectiveness of transfection. Among them, a naturally occurring material, chitosan (Chi), was widely studied, but the gene transfection efficiency was very low under physiological pH. Collagen (Col), the most abundant extracellular matrix (ECM), has demonstrated high cellular uptake efficiency, while Chi was recognized for its ability to promote endosomal escape. Here, we hypothesize that conjugating Col with Chi can enhance cellular uptake and hence the transfection efficiency. Specifically, we conjugated Col to Chi through amination, resulting in aminated Col-Chi (aCol-Chi), and compared the cellular uptake and gene transfection efficiency. The conjugation significantly increased the cellular uptake of aCol-Chi, which was 2.8 times higher than that of Chi, while the gene transfection efficiency of aCol-Chi was found 2.5 times higher than that of Chi. Moreover, aCol-Chi showed a higher 3D gene transfection efficiency than that of the aCol and Chi. Additionally, aCol-Chi exhibited potential for BMP2 secretion and its application in promoting osteogenic differentiation. This research highlights the development of an ECM-enhanced gene transfection reagent, aCol-Chi, with improved cellular uptake and gene transfection efficiency, holding potential for applications in gene therapy.
Myasthenia gravis is a rare disease characterized by autoantibody-driven impairment of neuromuscular junction activity. Standard-of-care therapy includes oral corticosteroids (OCS), despite associated complications. This study describes OCS-related complications and exacerbations in a real-world myasthenia gravis population. This retrospective longitudinal cohort study leveraged US claims data (January 2016-March 2023; Optum's de-identified Clinformatics® Data Mart Database) to identify patients with myasthenia gravis (International Classification of Diseases, Tenth Revision, Clinical Modification: G70.00/01). Patients were classified into non-OCS and OCS cohorts; the OCS cohort was further stratified into < 6-month, 6-month, and 12-month exposure groups (≥ 5 mg/day prednisone-equivalent; 12-month follow-up). Inverse probability treatment weighting balanced baseline characteristics. Weighted prevalence ratios of select complications (e.g., diabetes, fracture, hyperlipidemia, hypertension, infection, myocardial infarction, osteoporosis, stroke, glaucoma) and rate/risk ratios for exacerbations were calculated. The weighted population included 3297 patients in the non-OCS cohort and 418, 872, and 1243 patients in the <  6-month, 6-month, and 12-month OCS exposure groups, respectively. During follow-up, the <  6-month, 6-month, and 12-month OCS exposure groups had significantly higher infection risk versus non-OCS: weighted prevalence ratios (95% confidence interval) 1.6 (1.1-2.1), 1.5 (1.2-2.0), and 1.6 (1.3-2.0), respectively. Osteoporosis risk was similar in the <  6-month group but higher in the 6- and 12-month groups versus non-OCS: weighted prevalence ratios (95% confidence interval) 1.2 (0.9-1.6), 1.5 (1.2-1.8), and 1.7 (1.4-2.0), respectively. Oral corticosteroid exposure groups had more myasthenia gravis exacerbations during follow-up versus non-OCS. After adjusting for observable confounders, OCS exposure within the 12-month initiation period was associated with a higher burden of complications and exacerbations among patients with myasthenia gravis.
University students now use artificial intelligence (AI) tools in several academic activities, including information retrieval, writing support, and problem-solving. While these technologies may enhance learning efficiency, effective student engagement with AI requires relevant psychological characteristics as well as technology-related competencies. Earlier studies indicate that learner characteristics, including mindfulness, may relate to patterns of engagement with digital technologies. Mindfulness, AI literacy, and AI self-efficacy have been studied separately, but their combined relationships remain insufficiently examined. Accordingly, this study examined the associations among these three variables in university students and assessed whether specific dimensions of AI literacy were involved in the statistical association between mindfulness and students' self-rated readiness to use AI-supported tools for academic purposes. The study used a cross-sectional survey design. Undergraduate students at Shandong Xiehe University in China completed an online questionnaire. After screening the responses, 929 valid questionnaires were retained for analysis. Participants were between 18 and 22 years of age. Mindfulness, AI literacy, and AI self-efficacy were assessed using established self-report scales. The analysis first summarized the main study variables using descriptive statistics. Bivariate relationships among mindfulness, AI literacy, and AI self-efficacy were examined using Pearson correlation analysis. PROCESS Model 4 was applied with 5,000 bootstrap resamples to test the proposed indirect-association model. The results indicated positive relationships between mindfulness, AI literacy, and AI self-efficacy. Regression analyses also indicated that mindfulness showed significant relationships with each AI literacy dimension, namely AI awareness, AI usage, AI evaluation, and AI ethics. Mindfulness showed significant positive associations on multiple dimensions of AI self-efficacy. The mediation analyses identified AI literacy represented a significant indirect pathway linking mindfulness with AI self-efficacy. Specifically, the dimensions of AI awareness, AI usage, and AI evaluation showed significant indirect effects, AI ethics did not show consistent indirect effects across the tested models. The findings show that mindfulness was positively associated with AI literacy and AI self-efficacy among university students. They also suggest that students reporting higher AI literacy also reported greater perceived capability in using AI-supported tools, indicating that technological understanding may be statistically related to the association between mindfulness and perceived competence. The results show links between psychological awareness, AI literacy, and students' engagement with AI tools in higher education. The results may inform the development of AI literacy initiatives in higher education that support students' informed, insightful, and confident use of AI tools in academic contexts.
Clinical outcomes of critically ill COVID-19 patients admitted to intensive care units (ICUs) remain heterogeneous, and factors influencing mortality require further characterization. This retrospective study evaluated clinical outcomes among 1,344 adult patients with confirmed COVID-19 admitted to ICUs across four governmental hospitals in Kuwait between June 2020 and December 2022. Survival outcomes were assessed using Kaplan-Meier survival analysis and compared by demographic and clinical characteristics. Cox proportional hazards regression was applied to identify factors associated with mortality, while comorbidities and treatment patterns were evaluated in relation to patient outcomes. Survival probability declined from 98% at 5 days to 50% at one year. Kaplan-Meier analysis showed significant differences in survival according to age and diabetes status. Non-survivors were older (66 vs. 55 years, p < 0.001), had a higher prevalence of diabetes (60.9%) and hypertension (70.4%), and experienced longer hospital stays. Hypoxia was strongly associated with mortality (p < 0.001). In Cox regression analysis, adjusted for pandemic admission wave to account for evolving ICU management, increasing age (HR = 1.04 per year, 95% CI 1.03-1.04), fever (HR = 1.18, 95% CI 1.01-1.39), and chronic kidney disease (HR = 1.40, 95% CI 1.11-1.76) were associated with higher mortality. In contrast, anti-inflammatory drug use was associated with reduced risk (HR = 0.52, 95% CI 0.43-0.63) as was anticoagulant (HR = 0.80, 95% CI 0.66-0.97). Antifungal use was associated with increased mortality risk (HR = 1.68, 95% CI: 1.30-2.16); however, associations involving medications likely reflect underlying disease severity and treatment indication rather than direct causal effects. Sensitivity analysis using a split follow-up at day 30 demonstrated that antifungal-associated risk was concentrated during the late follow-up period (HR = 2.10, days 31-365), consistent with late-onset secondary fungal infections among patients with prolonged critical illness.
This network meta-analysis involved nine randomized controlled trials, comprising 595 participants (average age = 37.8 years, 55.3% female, 83.9% schizophrenia spectrum disorders), evaluating the comparative risk-benefit profiles of glucagon-like peptide-1 receptor agonists in individuals with obesity comorbid with mental illness. Outcomes included body weight (primary); body mass index (BMI); waist circumference; blood-based measures, including fasting plasma glucose, hemoglobin A1c (HbA1c), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides; systolic and diastolic blood pressure; death; all-cause discontinuation; adverse event-related discontinuation; serious adverse events (SAEs), injection site-related adverse events, headache, dizziness, nausea, vomiting, constipation, and diarrhea; psychiatric hospitalization; and changes in overall schizophrenia symptoms. Treatment arms comprised subcutaneous exenatide (S-EXE)(twice-daily [BID]/once-weekly [QW]), subcutaneous liraglutide (S-LIR)(once-daily [QD]), and subcutaneous semaglutide (S-SEM)(QW), alongside a control group (placebo, k = 8; non-placebo, k = 1). S-LIR(QD) and S-SEM(QW) were significantly associated with reduced body weight compared with control, with standardized mean differences (95% confidence intervals) of -0.945 ( - 1.784 to -0.106) and -2.101 ( - 2.978 to -1.224), respectively. S-LIR(QD) was associated with waist circumference and HbA1c level reductions, lower SAE incidences, and higher nausea, vomiting, and constipation incidences compared with the control. S-SEM(QW) was associated with reduced BMI, waist circumference, fasting plasma glucose, and HbA1c levels, and higher nausea, vomiting, and constipation compared with the control. Each drug did not differ from control regarding other outcomes. S-SEM(QW) may be the preferred treatment option, given its largest estimated effects versus control on body weight; however, its comparative ranking is uncertain due to sparse networks, substantial heterogeneity, and predominant indirect evidence.
The effect of placental transfusion on the nonvigorous intrauterine growth restricted (IUGR) neonates with pre-existing subclinical myocardial dysfunction and altered cerebral hemodynamics is largely unknown. The present study was planned to evaluate the effect of umbilical cord milking (UCM) on left ventricular output (LVO) of nonvigorous IUGR neonates of > 28-weeks' gestation. In the present randomized control trial, 74 nonvigorous IUGR neonates were randomly allocated to UCM (4-times squeezing of 20-cm intact cord, n = 37) and ECC (cord clamping within 30 s, n = 37). The primary outcome was LVO at 24 ± 2 h. Secondary outcomes were right ventricular output (RVO), superior vena cava blood flow (SVC flow), diastolic cardiac functions, venous hematocrit at 24 ± 2 h, peak total serum bilirubin (TSB), need and duration of respiratory support, in-hospital complications, mortality, and duration of hospital stay. Data were analyzed in SPSS version 27. LVO was comparable between the groups (255.53 ± 109.91 and 257.89 ± 103.59 mL/kg/min, in UCM and ECC groups, respectively; p = 0.925). Though all the other cardiac functions including RVO were similar, SVC flow was significantly less in neonates undergoing UCM. Mean hematocrit and need and duration of phototherapy were significantly higher in the UCM group, with comparable rates of polycythemia. Delivery room interventions, Apgar scores, incidences of in-hospital complications including hypoxic-ischemic encephalopathy, mortality, and duration of hospital stay were similar.  UCM increased venous hematocrit without affecting LVO or symptomatic polycythemia in nonvigorous IUGR neonates; however, the neurodevelopmental implications of reduced SVC flow warrant further evaluation.  CTRI/2024/02/063323, registered prospectively on 29/02/2024, https://trialsearch.who.int/ . • Umbilical cord milking (UCM) is a safe alternative to early cord clamping (ECC) among nonvigorous neonates >34 weeks' gestation. • UCM helps in achieving placental transfusion among nonvigorous intrauterine growth restricted neonates of >28 weeks' gestation without increasing the risk of polycythemia, compared to early cord clamping. • UCM results in higher hemoglobin, less need for delivery room cardiorespiratory support, and decreased rates of moderate-to-severe hypoxic-ischemic encephalopathy, compared to ECC.
Poverty is extensively acknowledged as a multidimensional phenomenon and has been the subject of extensive research all over the world. When it comes to child poverty, the impacts differ significantly due to the critical stages of physical, cognitive and socioemotional growth which make them vulnerable to the negative impacts of poverty. This paper analysed the impact of households' income sources on child's (0-17 years) fuzzy multidimensional poverty indicators in South Africa. The South African General Household Survey (GHS) datasets for the years 2017, 2018 and 2019 were used. The data were collected using the stratified two-stage sampling method with sampled households comprising 25,915, 25,224, and 20,083 children in 2017, 2018 and 2019, respectively. The fuzzy set methodology was used to compute child's multidimensional poverty indicator (MPI), which was later analysed with the Tobit regression model and treatment effects potential outcome framework using regression adjustment estimator. The results of the Tobit regression indicate that geography type, residence in Eastern Cape, North-West and Limpopo provinces, parental presence and income sources significantly (p < 0.01) influenced child's fuzzy multidimensional poverty. Additionally, children identified as Coloured, Indian/Asian and White and those who were biological children of household heads had significantly lower (p < 0.01) poverty. With respect to the Average Treatment Effect (ATE) and the Average Treatment Effect on the Treated (ATET), the results showed that children from households that were receiving social grants, salaries, income from business, remittances, pensions and other sources of income had significantly lower (p < 0.01) fuzzy MPI, when compared to the control group. In contrast, children from households that were receiving once off grants had significantly higher fuzzy MPI significantly (p < 0.01) higher compared to the control group. It was concluded that some income sources possess MPI reducing tendency. Therefore, development programmes to enhance households' access to them are recommended.
Nephrotic syndrome (NS) is the most common pediatric kidney disorder and may adversely affect oral health. This study compared oral health status, parental awareness, and dietary habits in children with NS with those of healthy controls. A case-control study was conducted among children aged 5-14 years in a tertiary care center in Kerala, India, including 151 children with NS diagnosed per International Study of Kidney Diseases in Children criteria and 151 age-matched healthy controls. Oral health was assessed by evaluating decayed, missing and filled teeth (DMFT to indicate permanent dentition and dmft to indicate primary dentition), oral hygiene, gingival health and enamel defects. Children with NS had significantly poorer oral hygiene (OHI-S: 0.70 ± 0.64 vs. 0.29 ± 0.54; p < 0.001) and greater gingival inflammation (GI: 0.39 ± 0.49 vs. 0.11 ± 0.31; p < 0.001). DMFT scores were higher in controls (1.48 ± 2.12 vs. 0.81 ± 1.72; p = 0.002). Age correlated positively with DMFT (NS: r = 0.268; non-NS: r = 0.401) and inversely with dmft (NS: r =  - 0.344; non-NS: r =  - 0.583; all p < 0.001). Children with NS had higher odds of infrequent dental visits (OR = 3.47, 95% CI 2.00-6.03) and regular brushing (OR = 3.47, 95% CI 2.00-6.03). Children with nephrotic syndrome (NS) have poorer oral hygiene and gingival health despite lower sugar intake and reported oral practices, underscoring the influence of dentition stage and the need for integrated dental care and targeted oral health education in pediatric NS management.
This study evaluated whether a vendor-neutral deep learning reconstruction (DLR) can improve image quality in accelerated T2-weighted imaging (T2WI) of the liver MRI acquired in a single breath-hold compared with routine T2WI. In this retrospective study, 86 patients who underwent nonenhanced 3-T liver MRI in August 2024 were included. Two board-certified radiologists independently assessed T2WI obtained using three protocols: (1) routine T2WI acquired with two breath-holds (Routine-2BH); (2) accelerated T2WI reconstructed with DLR acquired in a single breath-hold (SwiftMR-1BH); and (3) accelerated T2WI reconstructed with DLR acquired with two breath-holds (SwiftMR-2BH). Quantitative signal-to-noise ratio (SNR) and qualitative image quality, including sharpness, motion artifacts, spatial mismatch, and lesion conspicuity, were evaluated. The SwiftMR protocols reduced acquisition time by approximately 9 s compared with the routine protocol. Compared with Routine-2BH protocol, both SwiftMR protocols showed significantly higher sharpness and SNR (p < 0.001), although motion artifacts were more pronounced. Spatial mismatch scores were significantly lower with SwiftMR-1BH than with Routine-2BH and SwiftMR-2BH (p < 0.05). Among 49 patients with focal liver lesions, lesion conspicuity was generally higher with SwiftMR protocols, although not consistently significant. Overall, vendor-neutral DLR using SwiftMR restored the image quality of accelerated single-breath-hold T2WI for liver MRI, resulting in a higher SNR and overall image quality than routine two-breath-hold T2WI.
In this study, the biological activities of optimized extracts of Sparassis crispa, a medicinally important mushroom species, were comprehensively evaluated. Samples collected from Istanbul were extracted under specified conditions, and the optimization processes were performed using Response Surface Methodology (RSM) and Artificial Neural Network-Genetic Algorithm (ANN-GA). The obtained extracts were analyzed for antioxidant activities, including Total Antioxidant Status (TAS), Total Oxidant Status (TOS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, Ferric Reducing Antioxidant Power (FRAP), and Oxidative Stress Index (OSI), as well as anticholinesterase activities based on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. In addition, their antiproliferative effects against A549, MCF-7, and DU-145 cancer cell lines and phenolic compound profiles determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were evaluated. The findings revealed that ANN-GA optimization provided higher antioxidant capacity than RSM, as reflected by increased TAS, DPPH, and FRAP values in the ANN-GA extract (3.614 mmol/L, 95.89 mg Trolox equivalents/g, and 142.45 mg Trolox equivalents/g, respectively) compared with the RSM extract (3.179 mmol/L, 86.76 mg Trolox equivalents/g, and 118.67 mg Trolox equivalents/g, respectively). In addition, the ANN-GA extract showed lower TOS and OSI values (8.192 µmol/L and 0.227, respectively) than the RSM extract (9.343 µmol/L and 0.294, respectively), together with stronger anticholinesterase activity and more pronounced antiproliferative effects. Moreover, the ANN-GA optimized extract contained higher levels of biologically important phenolic compounds, including gallic acid, caffeic acid, and protocatechuic acid. Overall, the results demonstrate that ANN-GA based optimization is an effective strategy for increasing the recovery of biologically functional molecules and suggest that S. crispa may represent a promising natural resource for functional food, pharmaceutical, and biotechnological applications.
Monitoring contact patterns is important for assessing impact of public-health-and-social-measures (PHSM) during a pandemic, but existing methods, such as contact surveys or mobility data, have limitations. While the COVID-19 pandemic provided impetus for population-wide adoption of digital-contact-tracing (DCT), prior studies that utilised DCT to evaluate contact patterns evaluated temporal variations, lacking granularity pertaining to impact in at-risk groups. Population-wide DCT data was utilised to construct a cohort of SARS-CoV-2-infected community-dwelling adults (N = 544,259), evaluating temporal trends in contact patterns up to 5 days prior to positive SARS-CoV-2 test. Average contact number recorded on DCT was aggregated across four phases (baseline; tightened measures; relaxed measures; Omicron-surge). Incidence-rate-ratios (IRR) of average contacts was then compared across various phases, with the baseline phase as reference, via generalised linear models with a Poisson distribution. Results were stratified by vaccination status, comorbidities and occupation. Over the 8-month study period, we observe a downtrend in average contacts, versus baseline. Amongst fully-vaccinated cases, average contacts fall from 5.93 at baseline to 4.68 during tightened-measures (IRR = 0.78[95%CI = 0.77-0.79]), then increase to 5.23 when measures are relaxed, albeit still below baseline (IRR = 0.86[95%CI = 0.85-0.87]), and finally drop to 3.51 during Omicron (IRR = 0.58[95%CI = 0.57-0.58]). PHSM consistently impacts non-household contact, but does not initially affect household contact, which declines only during Omicron emergence, despite no change in PHSM. Frail individuals with comorbidities have higher non-household close-contacts, as do essential/frontline workers. DCT data can provide insight into contact patterns and enable assessment of PHSM's impact over pandemic phases. Population-wide digital-contact-tracing (DCT) is a technique used to measure how infection spreads from person to person in an outbreak. We used DCT to evaluate trends in contacts during successive waves of the SARS-CoV-2 pandemic. A decrease in the average number of contacts was observed over an 8-month period. Among fully-vaccinated cases, average contacts decreased from baseline when lockdowns and similar interventions were tightened; then increased when measures were relaxed, albeit still below baseline, and finally dropped again during the Omicron surge. Public health measures consistently impacted non-household contacts, but household contact was initially unaffected, only declining during Omicron despite no change in public health interventions. Frail individuals with comorbidities had higher non-household close-contacts, as did essential/frontline workers. DCT data can provide insight into contact patterns and enable assessment of public health impact over pandemic phases.
Investigate the impact of reticulocyte hemoglobin content (RetHe) on neurodevelopment in preterm infants. Retrospective cohort of infants born ≤366/7 weeks gestational age (GA) with neurodevelopmental testing post-discharge. Associations between neurodevelopment and average RetHe, lowest RetHe, and exposure time to low RetHe ( < 29 pg) were described and stratified by GA. RetHe over time and test Z-scores were assessed using multivariable linear regression. 52% of 381 infants (N = 199) had at least 1 low RetHe. Infants with abnormal development had lower average and minimum RetHe, and longer exposure to low RetHe (all p ≤ 0.003). RetHe was highest in infants born 32-33 weeks GA. Higher RetHe during postnatal weeks 1-5 was associated with higher Test of Infant Motor Performance Z-scores (p = 0.0048), with diminishing effect over time, but decreasing 12-month Bayley cognitive Z-scores (p = 0.0064). RetHe is associated with neurodevelopment and potentially has differential effects based on GA and postnatal age.
Digital breast tomosynthesis (DBT) has demonstrated improved cancer detection compared with digital mammography (DM) in trials of women aged 50-74, identifying more invasive cancers and detecting tumors at smaller sizes. However, its benefits for women over the age of 75 have not been examined. To assess whether DBT versus DM is associated with favorable tumor characteristics and detection of less conspicuous histologic subtypes in women aged ≥ 75 compared with those aged 67-74, thereby informing screening strategies and overdiagnosis risks. We conducted a SEER-Medicare retrospective cohort study of women aged ≥ 67 diagnosed with screen-detected ER+/HER2- breast cancer from 2015 to 2021. The primary exposure was screening modality (DBT vs. DM). Outcomes included tumor size, nodal involvement, grade, and histology (invasive lobular carcinoma [ILC] vs. other). Multivariable logistic regression was used to assess the association between screening modality and tumor characteristics among women aged 67-74 and ≥ 75. Among 17,201 women with screen-detected breast cancer, 43.6% were ≥ 75 at diagnosis and 60.4% were detected by DBT. In women aged 67-74, DBT was associated with higher odds of smaller tumors (adjusted odds ratio [aOR] = 1.18, 95% confidence interval [CI] = 1.08-1.29), grade I vs. II or III disease (aOR = 1.14, CI = 1.04-1.26), node-negative disease (aOR = 1.15, CI = 1.00-1.31, P = 0.048), and ILC histology (aOR = 1.29, CI = 1.13-1.48). In contrast, among women aged ≥ 75, DBT remained associated with higher odds of grade I tumors (aOR = 1.21, CI = 1.08-1.35) and node-negative disease (aOR = 1.18, CI = 1.00-1.39, P = 0.049), but was not significantly associated with smaller tumor size (aOR = 0.99, CI = 0.90-1.10) or ILC histology (aOR = 1.13, CI = 0.98-1.32). DBT was associated with lower grade and node negative disease in women ≥ 75, but not with smaller tumor size or ILC histology. The incremental advantage of DBT over DM may diminish with age, making the two modalities more comparable in women ≥ 75. Among screen-detected breast cancers, tomosynthesis was associated with lower-grade and node-negative tumors at ages 67–74 and ≥ 75, but smaller size and lobular histology only at 67–74, suggesting diminished benefit at ≥ 75.
Precise spatial understanding of complex anatomy is critical for preoperative planning in hepatobiliary surgery. Traditional CT and MRI imaging require mental reconstruction of anatomy from 2D slices, imposing substantial cognitive load. Although 3D reconstructions improve spatial understanding, they are typically displayed on 2D screens, limiting true depth perception. Virtual Reality (VR) visualization offers both stereoscopic depth and embodied interaction to improve spatial-anatomical understanding, yet its quantitative advantage over standard desktop visualization remains uncertain, especially regarding task complexity. In this randomized crossover study, 58 medical students analyzed 3D liver models of varying complexity using both VR and desktop visualization. Performance on lesion/vessel relations and lesion segment allocation tasks served as a measure of spatial-anatomical understanding, while visuospatial ability was assessed with the Mental Rotations Test. In complex models, VR significantly improved performance compared with desktop visualization (28.0 ± 3.3 vs. 26.4 ± 3.6; p = 0.002, d = 0.46), whereas results for simpler models were comparable. The VR advantage scaled with task complexity and correlated with higher visuospatial ability (r = 0.31, p = 0.018). These findings indicate that VR is associated with measurable advantages under higher task complexity, supporting its potential role in surgical education and preoperative planning, although the present design cannot isolate which immersive features drive this benefit.
Aggression is a major clinical issue in schizophrenia, but its biological basis remains unclear. This study examined the relationship between thyroid hormones, psychiatric symptoms, and aggression in drug-naïve schizophrenia (DNS) patients using causal inference methods. In a case-control study, we examined 161 DNS patients and 63 healthy controls. Aggression was assessed with the Modified Overt Aggression Scale (MOAS) and psychiatric symptoms with the Positive and Negative Syndrome Scale (PANSS). Serum thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were measured. DAG modeling, multivariable regression, mediation, and sensitivity analyses were conducted to characterize the relationships among thyroid hormones, psychiatric symptoms, and aggression. DNS patients exhibited significantly lower TSH levels than controls (t = - 24.81, p < 0.001). Within the schizophrenia cohort, the high-aggression group showed higher T3 levels (t = 2.24, p = 0.03) and more severe positive symptoms (t = 2.85, p < 0.001) than the low-aggression group. DAG analysis identified a direct association between T3 and aggression severity. In multivariable regression analyses, T3 remained significantly associated with aggression severity after adjustment for T4, age, and sex (β = 5.08, p = 0.01); and the association remained significant after further adjustment for positive and negative symptom dimensions (β = 4.99, p = 0.01). Mediation analyses found no evidence that positive or negative symptom dimensions explained this association. Sensitivity analyses supported the robustness of the findings. Higher T3 levels were associated with greater aggression severity in patients with schizophrenia.