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Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative condition marked by cognitive deterioration and changes in behavior. Acetylcholinesterase (AChE), which hydrolyzes acetylcholine, is a key drug target for treating AD. This research aimed to identify new AChE inhibitors using the IMPPAT database. We used known drugs as a basis to search for similar chemicals in the IMPPAT database and created a library of 127 plant-based compounds. Initial screening of these compounds was performed using molecular docking, followed by an analysis of their drug-likeness and ADMET properties. Compounds with favorable properties underwent density functional theory (DFT) calculations to assess their electronic properties such as HOMO-LUMO gap, electron density, and molecular orbital distribution. These descriptors provided insights into each compound’s reactivity, stability, and binding potential with AChE. Promising candidates were further evaluated through molecular dynamics (MD) simulations over 100 ns and MMPBSA analysis for the last 30 ns. Two compounds, Biflavanone (IMPHY013027) with a binding free energy of − 130.394 kcal/mol and Calomelanol J (IMPHY007737) with − 107.908 kcal/mol, demonstrated strong binding affinities compared to the reference molecule HOR, which has a binding free energy of − 105.132 kcal/mol. These compounds exhibited promising drug-ability profiles in both molecular docking and MD simulations, indicating their potential as novel AChE inhibitors for AD treatment. However, further experimental validation is necessary to verify their effectiveness and safety.

Abstract Natural deep eutectic solvents (NADES) are emerging, environment-friendly solvents that have garnered attention for their application in extracting phenolic compounds. This study investigated the effects of four synthetic NADES on polyphenols extracted from date seeds (DS) using choline chloride (ChCl) as a hydrogen-bond acceptor and lactic acid (La), citric acid (Citri), glycerol (Gly), and fructose (Fruc) as hydrogen-bond donors, in comparison with DS extracts extracted by conventional solvents (water, 70% methanol, and 70% ethanol). The antioxidant activity (DPPH), total phenolic content (TPC) and 6 phenolic compounds were determined using HPLC. The results showed that the ChCl–La and ChCl–Citri systems exhibited a high extraction efficiency regarding TPC, and DPPH in the DS extracts extracted by NADES compare to those DS extracts extracted with conventional solvents (p ˂ 0.001). HPLC results demonstrated that DS extracted by ChCl–La contained all measured phenolic compounds. Also gallic acid and catechin were the major compounds identified in the DS extracts. In addition DS extracted by ChCl–Citri and ChCl–Gly had the highest concentration of catechin. In conclusion, combining NADES is a promising and environment-friendly alternative to the conventional solvent extraction of phenolic compounds from DS.

Abstract Reusing of alloy has become a need of time due to the increasing demand, depletion of resources, and substantial increase in their price. The alloys used require a long-term stay in the oral cavity exposed to a wet environment, so they must have good wear resistance, biocompatibility, and mechanically good strength. In this study, the vertical marginal discrepancy, surface roughness, and microhardness of the new and recast nickel–chromium (base metal) alloys were evaluated. 125 wax patterns were fabricated from a customized stainless steel master die with a heavy chamfer cervical margin divided into 5 groups. Each group had 25 samples. Group A: 25 wax patterns were cast using 100% by weight of new alloy, Group B: the casting was done by using 75% new alloy and 25% alloy by weight, Group C: wax patterns were cast using 50% new alloy and 50% alloy, Group D: 25% new alloy and 75% alloy and Group E: 100% recast alloy. The vertical marginal discrepancy was measured by an analytical scanning microscope, microhardness was tested on a universal testing machine, and surface roughness was on a tester of surface roughness. Castings produced using new alloys were better than those obtained with reused alloys. Alloys can be reused till 50% by weight along with the new alloy and accelerated casting technique can be used to save the lab time to fabricate castings with acceptable vertical marginal discrepancy, microhardness, and surface roughness. This indicated that 50% recasting of (Ni–Cr) can be used as a good alternative for the new alloy from an economical point of view.

Natural deep eutectic solvents (NADES) are emerging, environment-friendly solvents that have garnered attention for their application in extracting phenolic compounds. This study investigated the effects of four synthetic NADES on polyphenols extracted from date seeds (DS) using choline chloride (ChCl) as a hydrogen-bond acceptor and lactic acid (La), citric acid (Citri), glycerol (Gly), and fructose (Fruc) as hydrogen-bond donors, in comparison with DS extracts extracted by conventional solvents (water, 70% methanol, and 70% ethanol). The antioxidant activity (DPPH), total phenolic content (TPC) and 6 phenolic compounds were determined using HPLC. The results showed that the ChCl–La and ChCl–Citri systems exhibited a high extraction efficiency regarding TPC, and DPPH in the DS extracts extracted by NADES compare to those DS extracts extracted with conventional solvents (p ˂ 0.001). HPLC results demonstrated that DS extracted by ChCl–La contained all measured phenolic compounds. Also gallic acid and catechin were the major compounds identified in the DS extracts. In addition DS extracted by ChCl–Citri and ChCl–Gly had the highest concentration of catechin. In conclusion, combining NADES is a promising and environment-friendly alternative to the conventional solvent extraction of phenolic compounds from DS. [ABSTRACT FROM AUTHOR]

Abstract The Saudi Cancer Registry reported in 2007 the 5-year observed survival for the most common cancer sites for the years 1994–2004. In this report we looked at the cancer survival in the period 2005–2009 and evaluated the trend over the 15 years period from 1994 to 2009. Cases of the top 14 cancer sites reported by the population based Saudi Cancer Registry from 1 January 2005 to December 31, 2009, were submitted for survival analysis. The vital status of those patients was collected. Analysis of survival for the above period was compared with the prior reported 2 periods (1994–1999, 2000–2004). In addition, analysis was done according to age, sex, disease stage and the province. Data of 25,969 patients of the commonest cancer sites were submitted. Of those 14,146 patients (54%) had complete demographic data available and vital status was reported. Thyroid cancer had the highest 5- year observed survival of 94% (95% confidence interval (CI) 93–95%)), followed by Breast (72%, 95% CI 71–74%). In hematological malignancies, Hodgkin’s Lymphoma had the highest 5-year survival of 86% (95% CI 84–88%). Survival rates has improved in most of the cancers sites for the studied periods except for lung, uterine and Hodgkin’s lymphoma which plateaued. Our study confirms a steady improvement in the 5-year observed survival over time for the majority of cancers. Our survival data were comparable to western countries. This data should be used by policy makers to improve on cancer care in the kingdom.

Psychosocial stress affects the relationship between prolactin (PRL) and cortisol (CORT). The dynamics of PRL and CORT changes under stress in human milk (HM) are largely unknown. We investigated how maternal stress related to recent life changes affects milk CORT and PRL concentrations. The study involved 116 mothers exclusively breastfeeding 5-month-old infants. Maternal psychological stress was evaluated using the Recent Life Changes Questionnaire (RLCQ). Stress response was determined by administering the cold pressor test and measuring CORT in saliva taken during and in milk collected after the test. Hormones concentrations were assayed using the ELISA method. The hierarchical regression models were run to test the association between maternal RLCQ, salivary CORT, and PRL, and CORT in milk. Maternal RLCQ correlated positively with the CORT in saliva, however, no direct association was found between RLCQ and PRL. After controlling for covariates, a positive association was found between salivary and milk CORT. A negative relationship was observed between salivary CORT and milk PRL. The results of the present study indicate that maternal psychological stress may affect the relationship between CORT and PRL in HM. In response to psychological stress, both hormones transported via milk can program infant development in the early postnatal period. [ABSTRACT FROM AUTHOR]

Although it is generally recognized that sleep quality, depressive symptoms, and cognitive functions are related respectively, the main ambiguity comes from difficulties in determining their cause-effect relationships. The present study aimed to explore the longitudinal causation relationships among sleep quality, depressive symptoms, and cognitive functions in older people with mild cognitive impairment (MCI). A total of 134 patients from 24 communities in Ningbo City, Zhejiang Province, China with MCI were interviewed at baseline, while 124 of them were re-interviewed 2 months later, and 122 were re-interviewed 4 months later. The Patient Health Questionnaire-9, the Pittsburgh Sleep Quality Index and the Montreal Cognitive Assessment Scale were assessed in the interview. Cross-lagged models were tested to disentangle the relationships among sleep quality, depressive symptoms, and cognitive functions using structural equation modeling with latent variables on the four-mouth longitudinal data. The correlation coefficients between sleep quality and depressive symptoms were significant showing the stability across time points of assessment, while the correlation coefficient of cognitive function was not significant (r = 0.159, p > 0.05). The results of index of model fit indicated that the cross-lagged model was acceptable (CFI = 0.934, TLI = 0.899, RMSEA = 0.075, χ2/df = 1.684). The results of cross-lagged model analysis supported the complete mediating role of depressive symptoms in the association between sleep quality and cognitive functions, where worse sleep quality may lead to more severe depressive symptoms, which in turn leads to more severe cognitive decline. In Conclusion, sleep quality is significantly correlated with cognitive functions in patients with mild cognitive impairment, which association is fully mediated by depressive symptoms. Approaches addressing sleep quality and depressive symptoms are recommended and hold promise for the management of mild cognitive impairment. [ABSTRACT FROM AUTHOR]

This retrospective cohort study conducted in Turkey between December 2020 and June 2022 aimed to assess antibiotic use, bacterial co-infections, and the associated factors on mortality in hospitalized patients with mild-to-severe COVID-19. Among the 445 patients, 80% received antibiotics, with fluoroquinolones being the most common choice, followed by beta-lactams and combinations. Various clinical and laboratory parameters, including symptoms, comorbidities, CCI, oxygen requirements, and CRP levels were observed to be elevated in the antibiotic group. Non-survivors had more ICU admissions and longer hospital stays compared to survivors. We conducted a multivariate Cox regression analysis to evaluate factors related to mortality. However, we did not find an association between antibiotic use and mortality [HR 2.7 (95% CI 0.4–20)]. The study identified significant factors associated with an antibiotic prescription, such as CCI (OR 1.6), CRP (OR 2.3), and ICU admission (OR 8.8), (p < 0.05). The findings suggest re-evaluating the necessity of antibiotics in COVID-19 cases based on clinical assessments, focusing on the presence of bacterial infections rather than empirical treatment. Further research is necessary to more accurately identify patients with bacterial co-infections who would benefit from antibiotic treatment. [ABSTRACT FROM AUTHOR]

The sample strategy employed in statistical parameter estimation issues has a major impact on the accuracy of the parameter estimates. Ranked set sampling (RSS) is a highly helpful technique for gathering data when it is difficult or impossible to quantify the units in a population. A bounded power logarithmic distribution (PLD) has been proposed recently, and it may be used to describe many real-world bounded data sets. In the current work, the three parameters of the PLD are estimated using the RSS technique. A number of conventional estimators using maximum likelihood, minimum spacing absolute log-distance, minimum spacing square distance, Anderson-Darling, minimum spacing absolute distance, maximum product of spacings, least squares, Cramer-von-Mises, minimum spacing square log distance, and minimum spacing Linex distance are investigated. The different estimates via RSS are compared with their simple random sampling (SRS) counterparts. We found that the maximum product spacing estimate appears to be the best option based on our simulation results for the SRS and RSS data sets. Estimates generated from SRS data sets are less efficient than those derived from RSS data sets. The usefulness of the RSS estimators is also investigated by means of a real data example. [ABSTRACT FROM AUTHOR]

Previous genome-wide association and replication study for job-related exhaustion indicated a risk variant, rs13219957 in the UST gene. Epidemiological studies suggest connection of stress-related conditions and dementia risk. Therefore, we first studied association of rs13219957 and register-based incident dementia using survival models in the Finnish National FINRISK study surveys (N = 26,693). The AA genotype of rs13219957 was significantly associated with 40% increased risk of all-cause dementia. Then we analysed the UST locus association with brain pathology in the Vantaa 85+ cohort and found association with tau pathology (Braak stage) but not with amyloid pathology. Finally, in the functional analyses, rs13219957 showed a highly significant association with two DNA methylation sites of UST, and UST expression. Thus, the results suggest a common risk variant for a stress-related condition and dementia. Mechanisms to mediate the connection may include differential DNA methylation and transcriptional regulation of UST. [ABSTRACT FROM AUTHOR]

Blood clots, which are composed of blood cells and a stabilizing mesh of fibrin fibers, are critical in cessation of bleeding following injury. However, their action is transient and after performing their physiological function they must be resolved through a process known as fibrinolysis. Internal fibrinolysis is the degradation of fibrin by the endogenous or innate presence of lytic enzymes in the bloodstream; under healthy conditions, this process regulates hemostasis and prevents bleeding or clotting. Fibrin-bound tissue plasminogen activator (tPA) converts nearby plasminogen into active plasmin, which is bound to the fibrin network, breaking it down into fibrin degradation products and releasing the entrapped blood cells. It is poorly understood how changes in the fibrin structure and lytic protein ratios influence the biochemical regulation and behavior of internal fibrinolysis. We used turbidity kinetic tracking and microscopy paired with mathematical modeling to study fibrin structure and lytic protein ratios that restrict internal fibrinolysis. Analysis of simulations and experiments indicate that fibrinolysis is driven by pore expansion of the fibrin network. We show that this effect is strongly influenced by the ratio of fibrin:tPAwhen compared to absolute tPA concentration. Thus, it is essential to consider relative protein concentrations when studying internal fibrinolysis both experimentally and in the clinic. An improved understanding of effective internal lysis can aid in development of better therapeutics for the treatment of bleeding and thrombosis. [ABSTRACT FROM AUTHOR]

Accurate and automatic segmentation of fibroglandular tissue in breast MRI screening is essential for the quantification of breast density and background parenchymal enhancement. In this retrospective study, we developed and evaluated a transformer-based neural network for breast segmentation (TraBS) in multi-institutional MRI data, and compared its performance to the well established convolutional neural network nnUNet. TraBS and nnUNet were trained and tested on 200 internal and 40 external breast MRI examinations using manual segmentations generated by experienced human readers. Segmentation performance was assessed in terms of the Dice score and the average symmetric surface distance. The Dice score for nnUNet was lower than for TraBS on the internal testset (0.909 ± 0.069 versus 0.916 ± 0.067, P < 0.001) and on the external testset (0.824 ± 0.144 versus 0.864 ± 0.081, P = 0.004). Moreover, the average symmetric surface distance was higher (= worse) for nnUNet than for TraBS on the internal (0.657 ± 2.856 versus 0.548 ± 2.195, P = 0.001) and on the external testset (0.727 ± 0.620 versus 0.584 ± 0.413, P = 0.03). Our study demonstrates that transformer-based networks improve the quality of fibroglandular tissue segmentation in breast MRI compared to convolutional-based models like nnUNet. These findings might help to enhance the accuracy of breast density and parenchymal enhancement quantification in breast MRI screening. [ABSTRACT FROM AUTHOR]

Power quality disturbance (PQD) is an important problem affecting the safe and stable operation of power system. Traditional single modal methods not only have a large number of parameters, but also usually focus on only one type of feature, resulting in incomplete information about the extracted features, and it is difficult to identify complex and diverse PQD types in modern power systems. In this regard, this paper proposes a multi-modal parallel feature extraction and classification model. The model pays attention to both temporal and spatial features of PQD, which effectively improves classification accuracy. And a lightweight approach is adopted to reduce the number of parameters of the model. The model uses Long Short Term Memory Neural Network (LSTM) to extract the temporal features of one-dimensional temporal modes of PQD. At the same time, a lightweight residual network (LResNet) is designed to extract the spatial features of the two-dimensional image modality of PQD. Then, the two types of features are fused into multi-modal spatio-temporal features (MSTF). Finally, MSTF is input to a Support Vector Machine (SVM) for classification. Simulation results of 20 PQD signals show that the classification accuracy of the multi-modal model proposed in this paper reaches 99.94%, and the parameter quantity is only 0.08 MB. Compared with ResNet18, the accuracy of the proposed method has been improved by 2.55% and the number of parameters has been reduced by 99.25%. [ABSTRACT FROM AUTHOR]

Physiological stress levels in response to sexual behavior stigma among men who have sex with men (MSM) in the United States (US) are understudied. The current study aims to explore the relationship between sexual behavior stigma and salivary cortisol both overall and stratified by race/ethnicity. If such an association exists, it may suggest that sexual behavior stigma can be physiologically measured or indicated by the presence of heightened salivary cortisol. A subsample of 667 MSM participants from the 2019 American Men's Internet Survey (AMIS; N = 10,129) submitted morning (AM) and evening (PM) saliva cortisol samples using at-home mail-in collection kits. Average daily cortisol and daily cortisol change were calculated; simple linear regressions estimated associations between cortisol measures and sexual behavior stigma characterized in four different ways (ever and recent experience of individual stigma items; average ever and recent experience of three stigma scales: stigma from family and friends, anticipated healthcare stigma, general social stigma). Participants reported a mean age of 36.0 years (SD = 14.9), with most being non-Hispanic white (n = 480, 72.0%), Hispanic (n = 164, 12.3%), or Black/African American (n = 146, 10.9%), and identified as homosexual/gay (n = 562, 84.3%). Reporting ever experiencing healthcare providers gossiping was significantly associated with higher PM cortisol (β = 0.12, p = 0.001) and higher average daily cortisol (β = 0.11, p = 0.004), while reporting ever experiencing police refusing to protect was associated with higher AM cortisol (β = 0.08, p = 0.03) and higher average daily cortisol (β = 0.09, p = 0.02). Recent experiences of stigma were not significant predictors of any measure of cortisol. Measures of salivary cortisol may be used to characterize sexual behavior stigma among MSM populations, however more insight is needed to determine its exact relationship and strength. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the use of novel optomyography (OMG) based smart glasses, OCOsense, for the monitoring and recognition of facial expressions. Experiments were conducted on data gathered from 27 young adult participants, who performed facial expressions varying in intensity, duration, and head movement. The facial expressions included smiling, frowning, raising the eyebrows, and squeezing the eyes. The statistical analysis demonstrated that: (i) OCO sensors based on the principles of OMG can capture distinct variations in cheek and brow movements with a high degree of accuracy and specificity; (ii) Head movement does not have a significant impact on how well these facial expressions are detected. The collected data were also used to train a machine learning model to recognise the four facial expressions and when the face enters a neutral state. We evaluated this model in conditions intended to simulate real-world use, including variations in expression intensity, head movement and glasses position relative to the face. The model demonstrated an overall accuracy of 93% (0.90 f1-score)—evaluated using a leave-one-subject-out cross-validation technique. [ABSTRACT FROM AUTHOR]

The increasing use of machine learning approaches on neuroimaging data comes with the important concern of confounding variables which might lead to biased predictions and in turn spurious conclusions about the relationship between the features and the target. A prominent example is the brain size difference between women and men. This difference in total intracranial volume (TIV) can cause bias when employing machine learning approaches for the investigation of sex differences in brain morphology. A TIV-biased model will not capture qualitative sex differences in brain organization but rather learn to classify an individual's sex based on brain size differences, thus leading to spurious and misleading conclusions, for example when comparing brain morphology between cisgender- and transgender individuals. In this study, TIV bias in sex classification models applied to cis- and transgender individuals was systematically investigated by controlling for TIV either through featurewise confound removal or by matching the training samples for TIV. Our results provide strong evidence that models not biased by TIV can classify the sex of both cis- and transgender individuals with high accuracy, highlighting the importance of appropriate modeling to avoid bias in automated decision making. [ABSTRACT FROM AUTHOR]

The use of extracorporeal membrane oxygenation (ECMO) is discussed to improve patients' outcome in severe COVID-19 with respiratory failure, but data on ECMO remains controversial. The aim of the study was to determine the characteristics of patients under invasive mechanical ventilation (IMV) with or without veno-venous ECMO support and to evaluate outcome parameters. Ventilated patients with COVID-19 with and without additional ECMO support were analyzed in a retrospective multicenter study regarding clinical characteristics, respiratory and laboratory parameters in day-to-day follow-up. Recruitment of patients was conducted during the first three COVID-19 waves at four German university hospitals of the Ruhr University Bochum, located in the Middle Ruhr Region. From March 1, 2020 to August 31, 2021, the charts of 149 patients who were ventilated for COVID-19 infection, were included (63.8% male, median age 67 years). Fifty patients (33.6%) received additional ECMO support. On average, ECMO therapy was initiated 15.6 ± 9.4 days after symptom onset, 10.6 ± 7.1 days after hospital admission, and 4.8 ± 6.4 days after the start of IMV. Male sex and higher SOFA and RESP scores were observed significantly more often in the high-volume ECMO center. Pre-medication with antidepressants was more often detected in survivors (22.0% vs. 6.5%; p = 0.006). ECMO patients were 14 years younger and presented a lower rate of concomitant cardiovascular diseases (18.0% vs. 47.5%; p = 0.0004). Additionally, cytokine-adsorption (46.0% vs. 13.1%; p < 0.0001) and renal replacement therapy (76.0% vs. 43.4%; p = 0.0001) were carried out more frequently; in ECMO patients thrombocytes were transfused 12-fold more often related to more than fourfold higher bleeding complications. Undulating C-reactive protein (CRP) and massive increase in bilirubin levels (at terminal stage) could be observed in deceased ECMO patients. In-hospital mortality was high (Overall: 72.5%, ECMO: 80.0%, ns). Regardless of ECMO therapy half of the study population deceased within 30 days after hospital admission. Despite being younger and with less comorbidities ECMO therapy did not improve survival in severely ill COVID-19 patients. Undulating CRP levels, a massive increase of bilirubin level and a high use of cytokine-adsorption were associated with worse outcomes. In conclusion, ECMO support might be helpful in selected severe cases of COVID-19. [ABSTRACT FROM AUTHOR]

The study aims to assess the thickness of the retinal outer nuclear layer (ONL), ellipsoid zone (EZ) and photoreceptor outer segment (POS) band in various macular regions and its associations with axial length and other parameters. Participants of the Beijing Eye Study 2011 underwent a series of examinations including spectral-domain optical coherence tomography of the macula. The current study included 2213 participants without retinal or optic nerve diseases (age: 61.7 ± 8.4 years; range 50–93 years); axial length: 23.15 ± 0.95 mm; range 18.96–29.15 mm). The ONL (fovea: 98.9 ± 8.8 µm), EZ (fovea: 24.1 ± 0.5 µm) and POS band (fovea: 24.3 ± 3.5 µm) were the thickest (P < 0.001) in the fovea (defined as the thinnest central point), followed by the temporal inner, nasal inner, inferior inner, superior inner, inferior outer, temporal outer, nasal outer, and superior outer region. In multivariable analysis, a thicker retinal ONL was associated (correlation coefficient r: 0.40) with shorter axial length (beta: − 0.14; P < 0.001) and shorter disc–fovea distance (beta: − 0.10; P = 0.001), after adjusting for younger age (beta: − 0.26; P < 0.001), male sex (beta: 0.24; P < 0.001), lower serum cholesterol concentration (beta: − 0.05; P = 0.04), and thicker subfoveal choroidal thickness (beta: 0.08; P < 0.001). The POS thickness increased with shorter axial length (beta: − 0.06; P < 0.001) and shorter optic disc–fovea distance (beta: − 0.05; P = 0.03), after adjusting for younger age (beta: − 0.34; P < 0.001), male sex (beta: 0.15; P < 0.001), and thicker subfoveal choroidal thickness (beta: 0.24; P < 0.001). As a conclusion, the photoreceptor ONL, EZ and POS band vary in thickness between different macular regions and differ in their correlations with axial length, disc–fovea distance, age, sex, and subfoveal choroidal thickness. The ONL thickness decrease with longer axial length and longer disc–fovea distance may point to an axial elongation-associated retinal stretching in the macula. [ABSTRACT FROM AUTHOR]

The validation of the accuracy of the quantification software in computed tomography (CT) images is very challenging. Therefore, we proposed a CT imaging phantom that accurately represents patient-specific anatomical structures and randomly integrates various lesions including disease-like patterns and lesions of various shapes and sizes using silicone casting and three-dimensional (3D) printing. Six nodules of various shapes and sizes were randomly added to the patient's modeled lungs to evaluate the accuracy of the quantification software. By using silicone materials, CT intensities suitable for the lesions and lung parenchyma were realized, and their Hounsfield unit (HU) values were evaluated on a CT scan of the phantom. As a result, based on the CT scan of the imaging phantom model, the measured HU values for the normal lung parenchyma, each nodule, fibrosis, and emphysematous lesions were within the target value. The measurement error between the stereolithography model and 3D-printing phantoms was 0.2 ± 0.18 mm. In conclusion, the use of 3D printing and silicone casting allowed the application and evaluation of the proposed CT imaging phantom for the validation of the accuracy of the quantification software in CT images, which could be applied to CT-based quantification and development of imaging biomarkers. [ABSTRACT FROM AUTHOR]

Recently, short online videos have been highly recognized by video market users and have developed rapidly. This study aims to explore why users enjoy watching and sharing short online videos by applying the theory of flow experience. Previous research has extensively examined traditional video arts such as TV and movies and text or image based, while research on short online videos has increased only in recent years. To improve the precision and comprehensiveness of the research, social influence is also used as a variable. This study takes the short video representative platform DouYin as a case study and the Chinese user market as the background. Through questionnaires, 406 users' data about short online video experiences were collected. After statistical analysis, the study finds that flow experience has a significant impact on participative behaviour and sharing behaviour for short online videos. According to further analyses, the flow experience, social norms, perceived critical mass and participative and sharing behaviour constitute three groups of mediating relationships. Finally, the discussion of the research results provides help to broaden the academic scope of the flow experience and video art, improve the short online video platform environment, and upgrade short online video services. [ABSTRACT FROM AUTHOR]

Both sex/gender and socioeconomic differences have been reported in the prevalence of modifiable risk factors for dementia. However, it remains unclear whether the associations between modifiable risk factors for dementia and incident dementia differ by sex/gender or socioeconomic status. This study aimed to investigate sex/gender and socioeconomic differences in the associations of modifiable risk factors with incident dementia using a life-course perspective. We used data from the English Longitudinal Study of Ageing (2008/2009 to 2018/2019). A total of 8,941 individuals were included [mean (standard deviation) age, 66.1 ± 9.8 years; 4,935 (55.2%) were women]. No overall sex/gender difference in dementia risk was found. Dementia risk was higher among those who experienced childhood deprivation [hazard ratio (HR) = 1.51 (1.17; 1.96)], lower occupational attainment [HR low versus high = 1.60 (1.23; 2.09) and HR medium versus high = 1.53 (1.15; 2.06)], and low wealth [HR low versus high = 1.63 (1.26; 2.12)]. Though different associations were found among the subgroups, there might be a sex/gender difference in dementia risk only for low cognitive activity, suggesting a higher risk for women [HR = 2.61 (1.89; 3.60)] compared to men [HR = 1.73 (1.20; 2.49)]. No consistent socioeconomic differences in modifiable dementia risk were found. A population-based approach that tackles inequalities in dementia risk profiles directly may be more effective than individual approaches in dementia prevention. [ABSTRACT FROM AUTHOR]

Sleep is a complex process and is needed both in health and illness. Deprivation of sleep is known to have multiple negative physiological effects on people's bodies and minds. Despite the awareness of these harmful effects, previous studies have shown that sleep is poor among hospitalised patients. We utilized an observational design with 343 patients recruited from medical and surgical units in 12 hospitals located in nine Spanish regions. Sociodemographic and clinical characteristics of patients were collected. Sleep quality at admission and during hospitalisation was measured by the Pittsburgh Sleep Quality Index. Sleep quantity was self-reported by patients in hours and minutes. Mean PSQI score before and during hospitalisation were respectively 8.62 ± 4.49 and 11.31 ± 4.04. Also, inpatients slept about an hour less during their hospital stay. Lower educational level, sedative medication intake, and multi-morbidity was shown to be associated with poorer sleep quality during hospitalisation. A higher level of habitual physical activity has shown to correlate positively with sleep quality in hospital. Our study showed poor sleep quality and quantity of inpatients and a drastic deterioration of sleep in hospital versus at home. These results may be helpful in drawing attention to patients' sleep in hospitals and encouraging interventions to improve sleep. [ABSTRACT FROM AUTHOR]

The present study aimed at investigating the influence of personality on both anticipatory stress vulnerability and the effectiveness of coping strategies in an occupational stressful context. Following assessment of individual personality traits (Big Five Inventory), 147 volunteers were exposed to the anticipation of a stressful event. Anxiety and cardiac reactivity were assessed as markers of vulnerability to anticipatory stress. Participants were then randomly assigned to three groups and subjected to a 5-min intervention: relaxation breathing, relaxation breathing combined with cardiac biofeedback, and control. The effectiveness of coping interventions was determined through the cardiac coherence score achieved during the intervention. Higher neuroticism was associated with higher anticipatory stress vulnerability, whereas higher conscientiousness and extraversion were related to lower anticipatory stress vulnerability. Relaxation breathing and biofeedback coping interventions contributed to improve the cardiac coherence in all participants, albeit with greater effectiveness in individuals presenting higher score of openness to experience. The present findings demonstrated that personality traits are related to both anticipatory stress vulnerability and effectiveness of coping interventions. These results bring new insights into practical guidelines for stress prevention by considering personality traits. Specific practical applications for health professionals, who are likely to manage stressful situations daily, are discussed. [ABSTRACT FROM AUTHOR]

Previous studies investigated the frequency of different adverse events of COVID-19 vaccines. However, this study compares these adverse events between the two main COVID-19 vaccines used in Saudi Arabia (Pfizer-BioNTech and Oxford-AstraZeneca) using telemedicine technology. A cross-sectional study was conducted among 958 individuals, 7 days after receiving either Pfizer-BioNTech or Oxford-AstraZeneca vaccines during June 2021. Immediate adverse events were reported by 1.04% and 2.09% for Pfizer-BioNTech and Oxford-AstraZeneca vaccines, respectively, with no serious events. Recipients of Pfizer-BioNTech vaccine had a higher percentage of local adverse events (24.8% versus 9.8% in AstraZeneca vaccine). The most common reported systemic adverse events in both vaccines respectively were general fatigue (23.1% and 25.1%), fever (18.5% and 27.2%), myalgia (20.6% and 20.3%), and headache (15.2% and 17.2%). No significant difference was recorded between both vaccines regarding overall systemic adverse events; however, they were more frequent following the first dose of AstraZeneca vaccine compared to Pfizer-BioNTech vaccine, while the reverse was observed for the second dose. Adverse events were more frequent in females and younger age groups for both vaccines. Most of systemic and local adverse events were mild in nature. Further cohort studies are recommended to investigate the long-term adverse events of COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

Identification of structural variants (SVs) breakpoints is important in studying mutations, mutagenic causes, and functional impacts. Next-generation sequencing and whole-genome optical mapping are extensively used in SV discovery and characterization. However, multiple platforms and computational approaches are needed for comprehensive analysis, making it resource-intensive and expensive. Here, we propose a strategy combining optical mapping and cas9-assisted targeted nanopore sequencing to analyze SVs. Optical mapping can economically and quickly detect SVs across a whole genome but does not provide sequence-level information or precisely resolve breakpoints. Furthermore, since only a subset of all SVs is known to affect biology, we attempted to type a subset of all SVs using targeted nanopore sequencing. Using our approach, we resolved the breakpoints of five deletions, five insertions, and an inversion, in a single experiment. [ABSTRACT FROM AUTHOR]

This study examined whether resilience capacity moderates the association of daily perceived stress and affect with cortisol diurnal slope among relocated emerging adults. Relocated undergraduates (N = 98; aged 18–25 years) were recruited from three groups: Resilient, Vulnerable, and Control. The Resilient group required Risky Family Questionnaire (RFQ) scores ≥ 29 and Brief Resilience Scale (BRS) scores ≥ 3.6. The Vulnerable group required RFQ scores ≥ 29 and BRS scores ≤ 3. The comparison Control group required RFQ scores ≤ 21 and T-scores < 60 on PROMIS anxiety and depression symptoms. Mixed-effects models were used to test the unique associations of perceived stress, negative affect, and positive affect x group interactions (predictors) on diurnal cortisol slope (outcome) across 14 consecutive days. The Resilient group did not moderate the associations between daily stress or affect on cortisol diurnal slope. Instead, both the Resilient and Vulnerable groups with early family risk, showed a steeper diurnal slope unique to higher stress and a flatter slope unique to higher negative affect. Results suggest that riskier early family life was significantly associated with altered cortisol diurnal slope outcomes to stress (i.e., demand) and negative affect (i.e., distress). These associations were not attenuated by current resilience capacity. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) are among the most important biofilm-forming pathogens responsible for hard-to-treat infections. Looking for alternatives to antibiotics that prevent biofilm formation, we investigated the effects of manuka honey on the transcriptional profile of genes essential for staphylococcal biofilm formation using qRT-PCR. mRNA from two hospital MRSA strains (strong and weak biofilm producer) were isolated after 4, 8, 12 and 24 h from cells grown in biofilm. Manuka honey at 1/2 minimum biofilm inhibition concentration (MBIC) significantly reduced MRSA cell viability in biofilm. Manuka honey downregulated the genes encoding laminin- (eno), elastin- (ebps) and fibrinogen binding protein (fib), and icaA and icaD involved in biosynthesis of polysaccharide intercellular adhesin in both weakly and strongly adhering strain compared to the control (untreated biofilm). Expression levels of cna (collagen binding protein) and map/eap (extracellular adherence protein—Eap) were reduced in weakly adhering strain. The lowest expression of investigated genes was observed after 12 h of manuka honey treatment at 1/2 MBIC. This study showed that the previously unknown mechanism of manuka honey action involved inhibition of S. aureus adhesion due to reduction in expression of crucial genes associated with staphylococcal biofilm. [ABSTRACT FROM AUTHOR]

Synapse loss occurs early and correlates with cognitive decline in Alzheimer's disease (AD). Synaptotoxicity is driven, at least in part, by amyloid-beta oligomers (Aβo), but the exact synaptic components targeted by Aβo remain to be identified. We here tested the hypotheses that the post-synaptic protein Neuroligin-1 (NLGN1) is affected early in the process of neurodegeneration in the hippocampus, and specifically by Aβo, and that it can modulate Aβo toxicity. We found that hippocampal NLGN1 was decreased in patients with AD in comparison to patients with mild cognitive impairment and control subjects. Female 3xTg-AD mice also showed a decreased NLGN1 level in the hippocampus at an early age (i.e., 4 months). We observed that chronic hippocampal Aβo injections initially increased the expression of one specific Nlgn1 transcript, which was followed by a clear decrease. Lastly, the absence of NLGN1 decreased neuronal counts in the dentate gyrus, which was not the case in wild-type animals, and worsens impairment in spatial learning following chronic hippocampal Aβo injections. Our findings support that NLGN1 is impacted early during neurodegenerative processes, and that Aβo contributes to this effect. Moreover, our results suggest that the presence of NLGN1 favors the cognitive prognosis during Aβo-driven neurodegeneration. [ABSTRACT FROM AUTHOR]

Associations of sleep characteristics with mild cognitive impairment (MCI) have been examined in cross-sectional, but rarely in longitudinal studies. Incident MCI and sleep characteristics were assessed in 1,890 participants of the first and second follow-up of the Heinz Nixdorf Recall study, a population-based cohort study in Germany (age at first follow-up 50−80 years, mean follow-up 5.2 years). MCI was assessed with extensive cognitive tests. Sleep questionnaires including PSQI (Pittsburgh Sleep Quality Index) were used to assess sleep quality, sleep disturbances, time asleep, and time in bed. Relative risks (RR) of developing MCI when exposed to sleep characteristics were assessed in regression models adjusted for sociodemographic and cardiovascular risk factors. Poor sleep quality (PSQI > 5) (RR = 1.43, 95% CI: 1.12−1.82, fully adjusted, reference: PSQI ≤ 5) and difficulties initiating sleep (almost nightly versus never) (RR = 1.40, 0.94−2.08) were associated with incident MCI. For time in bed, the risk of MCI was increased for ≤ 5 hours (RR = 2.86, 1.24─6.60, reference:7 to <8 hours). In this longitudinal study with older participants, MCI risk was increased in persons with poor sleep quality, difficulties initiating sleep, and short time in bed. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a highly fatal disease recognized as a growing global health crisis worldwide. Currently, no curative treatment is available for early-to-intermediate stage HCC, characterized by large and/or multifocal tumors. If left untreated, HCC rapidly progresses to a lethal stage due to favorable conditions for metastatic spread. Mechanochemical disruption of cellular structures can potentially induce phenotypic alterations in surviving tumor cells that prevent HCC progression. In this paper, HCC response to mechanical vibration via high-intensity focused ultrasound and a chemical disruptive agent (ethanol) was examined in vitro and in vivo. Our analysis revealed that mechanochemical disruption caused a significant overproduction of reactive oxygen species (ROS) in multiple HCC cell lines (HepG2, PLC/PRF/5, and Hep3B). This led to a decrease in cell viability and long-term proliferation due to increased expression and activity of death receptors TNFR1 and Fas. The cells that survived mechanochemical disruption had a reduced expression of cancer stem cell markers (CD133, CD90, CD49f) and a diminished colony-forming ability. Mechanochemical disruption also impeded HCC migration and their adhesion to vascular endothelium, two critical processes in hematogenous metastasis. The HCC transformation to a non-tumorigenic phenotype post mechanochemical disruption was confirmed by a lack of tumor spheroid formation in vitro and complete tumor regression in vivo. These results show that mechanochemical disruption inhibits uncontrolled proliferation and reduces tumorigenicity and aggressiveness of HCC cells through ROS overproduction and associated activation of TNF- and Fas-mediated cell death signaling. Our study identifies a novel curative therapeutic approach that can prevent the development of aggressive HCC phenotypes. [ABSTRACT FROM AUTHOR]

Many people experience mild stress in modern society which raises the need for an improved understanding of psychophysiological responses to stressors. Heart rate variability (HRV) may be associated with a flexible network of intricate neural structures which are dynamically organized to cope with diverse challenges. HRV was obtained in thirty-three healthy participants performing a cognitive task both with and without added stressors. Markers of neural autonomic control and neurovisceral complexity (entropy) were computed from HRV time series. Based on individual anxiety responses to the experimental stressors, two subgroups were identified: anxiety responders and non-responders. While both vagal and entropy markers rose during the cognitive task alone in both subgroups, only entropy decreased when stressors were added and exclusively in anxiety responders. We conclude that entropy may be a promising marker of cognitive tasks and acute mild stress. It brings out a new central question: why is entropy the only marker affected by mild stress? Based on the neurovisceral integration model, we hypothesized that neurophysiological complexity may be altered by mild stress, which is reflected in entropy of the cardiac output signal. The putative role of the amygdala during mild stress, in modulating the complexity of a coordinated neural network linking brain to heart, is discussed. [ABSTRACT FROM AUTHOR]

The pathophysiology of malarial anemia is multifactorial and incompletely understood. We assessed mechanistic and risk factors for post-malarial anemia in Ghanaian and Gabonese children with severe P. falciparum malaria treated with parenteral artesunate followed by an oral artemisinin-combination therapy. We analyzed data from two independent studies in which children were followed on Days 7,14, and 28 after treatment with artesunate. Specific hematological parameters included the presence of hemoglobinopathies and erythropoietin. Presence of once-infected erythrocytes was assessed by flow cytometry in a sub-population. Of 143 children with a geometric mean parasitemia of 116,294/µL (95% CI: 95,574–141,505), 91 (88%) had anemia (Hb < 10 g/dL) at presentation. Hemoglobin increased after Day 7 correlating with increased erythropoiesis through adequate erythropoietin stimulation. 22 children (24%) remained anemic until Day 28. Post-artesunate delayed hemolysis was detected in 7 children (5%) with only minor differences in the dynamics of once-infected erythrocytes. Hyperparasitemia and hemoglobin at presentation were associated with anemia on Day 14. On Day 28 only lower hemoglobin at presentation was associated with anemia. Most children showed an adequate erythropoiesis and recovered from anemia within one month. Post-artesunate delayed hemolysis (PADH) and hyperparasitemia are associated with early malarial anemia and pre-existing anemia is the main determinant for prolonged anemia. [ABSTRACT FROM AUTHOR]

Leukemia-associated antigens (LAAs) and HLA-I epitopes published previously have shown promise in inducing leukemia-specific T cell responses. However, the clinical responses are limited, and clinical effectiveness is yet to be achieved. Limitations, among others, being the LAAs themselves, the indirect approach to HLA-I epitope identification by reverse immunology, and the use of single or few LAAs and HLA-I epitopes, which limits the spectrum of inducible tumor-specific T cells. Use of a direct approach to identify naturally processed and presented HLA-I epitopes from LAAs, and higher numbers of antigens for T cell-mediated immunotherapy for leukemia may enhance clinical responses and broaden clinical effectiveness. In a prior study we used immunoaffinity purification of HLA-I peptide complexes from the differentiated myeloid tumor cell lines MUTZ3 and THP1 coupled to high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). From this we identified in the current study seven new HLA-I epitopes and the corresponding LAAs for myeloid leukemia. In comparison, the myeloid HLA-I epitopes reported here were generally stronger HLA-binders that induce stronger T cell responses than those previously published, and their source LAAs had higher immunogenicity, higher expression levels in myeloid tumors cells compared to normal hemopoietin and other major normal tissues, and more protein interaction partners, and they are targeted by CD8 T cells in CML patients. This study analyses and compares the LAAs and HLA-I epitopes based on various immunotherapeutic targets selection criteria, and highlights new targets for T cell-mediated immunotherapy for leukemia. [ABSTRACT FROM AUTHOR]

Cattle imported from the Iberian Peninsula spread throughout America in the early years of discovery and colonization to originate Creole breeds, which adapted to a wide diversity of environments and later received influences from other origins, including zebu cattle in more recent years. We analyzed uniparental genetic markers and autosomal microsatellites in DNA samples from 114 cattle breeds distributed worldwide, including 40 Creole breeds representing the whole American continent, and samples from the Iberian Peninsula, British islands, Continental Europe, Africa and American zebu. We show that Creole breeds differ considerably from each other, and most have their own identity or group with others from neighboring regions. Results with mtDNA indicate that T1c-lineages are rare in Iberia but common in Africa and are well represented in Creoles from Brazil and Colombia, lending support to a direct African influence on Creoles. This is reinforced by the sharing of a unique Y-haplotype between cattle from Mozambique and Creoles from Argentina. Autosomal microsatellites indicate that Creoles occupy an intermediate position between African and European breeds, and some Creoles show a clear Iberian signature. Our results confirm the mixed ancestry of American Creole cattle and the role that African cattle have played in their development. [ABSTRACT FROM AUTHOR]

Population-based data investigating generational differences in the risk of incident cardiovascular disease (CVD) and its risk determinants are rare. We examined the 6-year incidence of CVD and its risk factors in first- and second-generation ethnic Indians living in Singapore. 1749 participants (mean age [SD]: 55.5 [8.8] years; 47.5% male) from a population-based, longitudinal study of Indian adults were included for incident CVD outcome. Incident CVD was defined as self-reported myocardial infarction, angina pectoris or stroke which developed between baseline and follow-up. CVD-related risk factors included incident diabetes, hypertension, hyperlipidemia, obesity and chronic kidney disease (CKD). For incident CVD outcome, of the 1749 participants, 406 (23.2%) and 1343 (76.8%) were first and second-generation Indians, respectively. Of these, 73 (4.1%) reported incident CVD. In multivariable models, second-generation individuals had increased risk of developing CVD (RR = 2.04; 95% CI 1.04, 3.99; p = 0.038), hyperlipidemia (RR = 1.27; 95% CI 1.06, 1.53; p = 0.011), and CKD (RR = 1.92; 95% CI 1.22, 3.04; p = 0.005), compared to first-generation Indians. Second-generation Indians have increased risk of developing CVD and its associated risk factors such as hyperlipidemia and CKD compared to first-generation immigrants, independent of traditional CVD risk factors. More stratified and tailored CVD prevention strategies on second and subsequent generations of Indian immigrants in Singapore are warranted. [ABSTRACT FROM AUTHOR]

The current study examined whether the steroid hormone, 17β-estradiol (E2) can exert long-lasting beneficial effects upon axonal health, synaptic plasticity, dementia-related amyloid-beta (Aβ) protein expression, and hippocampal-dependent cognitive function in an animal model of chronic cerebral hypoperfusion and vascular dementia (VaD). Chronic cerebral hypoperfusion and VaD was induced by bilateral common carotid artery occlusion (BCCAO) in adult male Sprague Dawley rats. Low dose E2 administered for the first 3-months after BCCAO exerted long-lasting beneficial effects, including significant neuroprotection of hippocampal CA1 neurons and preservation of hippocampal-dependent cognitive function when examined at 6-months after BCCAO. E2 treatment also prevented BCCAO-induced damage to hippocampal myelin sheaths and oligodendrocytes, enhanced expression of the synaptic proteins synaptophysin and PSD95 in the hippocampus, and prevented BCCAO-induced loss of total and mushroom dendritic spines in the hippocampal CA1 region. Furthermore, E2-treatment also reduced BCCAO induction of dementia-related proteins expression such as p-tau (PHF1), total ubiquitin, and Aβ1-42, when examined at 6 m after BCCAO. Taken as a whole, the results suggest that low-dose E2 replacement might be a potentially promising therapeutic modality to attenuate or block negative neurological consequences of chronic cerebral hypoperfusion and VaD. [ABSTRACT FROM AUTHOR]

Neurexins are transmembrane synaptic cell adhesion molecules involved in the development and maturation of neuronal synapses. In the present study, we report that Nrxn3β is processed by the metalloproteases ADAM10, ADAM17, and by the intramembrane-cleaving protease γ-secretase, producing secreted neurexin3β (sNrxn3β) and a single intracellular domain (Nrxn3β-ICD). We further completed the full characterization of the sites at which Nrxn3β is processed by these proteases. Supporting the physiological relevance of the Nrxn3β processing, we demonstrate in vivo a significant effect of the secreted shedding product sNrxn3β on the morphological development of adult newborn neurons in the mouse hippocampus. We show that sNrxn3β produced by the cells of the dentate gyrus increases the spine density of newborn neurons whereas sNrxn3β produced by the newborn neuron itself affects the number of its mossy fiber terminal extensions. These results support a pivotal role of sNrxn3β in plasticity and network remodeling during neuronal development. [ABSTRACT FROM AUTHOR]