Miracle-dz/UniFAR-FTUs huggingface dataset:
Angiotensin II and hypoxia induce autophagy in cardiomyocytes via activating specific protein kinase C subtypes.

Background The purpose of this study was to explore the role of protein kinase C (PKC) isozymes and reactive oxygen species (ROS) in hypoxia and angiotensin (Ang) II-induced autophagy. Methods Primary cardiomyocytes were isolated from Sprague-Dawley (SD) neonatal rats and cultured in hypoxia and/or Ang II conditions. Dihydroethidium fluorescence staining was used to detect the content of ROS. Cardiomyocyte autophagy was determined using Monodansylcadaverine fluorescence staining and Western blot. We also inhibited ROS production to explore the relationship between ROS and autophagy. ELISA was used to detect the contents of PKC δ and PKC ε. After inhibition of PKC δ activation and PKC ε expression by lentiviral siRNA, ROS content and autophagy of cultured cardiomyocytes were detected. Results Hypoxia and Ang II stimulation increased autophagy in cardiomyocytes, accompanied by increased intracellular ROS production. Inhibiting ROS following hypoxia or Ang II stimulation significantly suppressed autophagy in comparison with hypoxia or Ang II stimulation group. Inhibiting PKC δ significantly reduced ROS production and autophagy activity following hypoxia or accompanied with Ang II stimulation except Ang II stimulation alone. Knockdown of PKC ε notably decreased ROS production and autophagy in response to Ang II alone and in combination with hypoxia rather than hypoxia alone. Conclusions Both hypoxia and Ang II stimulation can induce autophagy in cardiomyocytes through increasing intracellular ROS. However, hypoxia and Ang II stimulation induced myocardial autophagy via PKC δ and PKC ε, respectively.
Additivity of digestible energy and nutrient concentrations in hatchery byproducts fed to nursery pigs

Objective The objective was to test additivity of digestible energy and nutrient concentrations in the hatchery byproduct mixture fed to nursery pigs. Methods In the previous studies, energy, phosphorus, calcium, and amino acid digestibility of infertile eggs, unhatched eggs, culled chicks, and a mixture of 3 hatchery byproduct ingredients was determined in nursery pigs (initial body weight = 9.4 to 14.2 kg). An additivity test was conducted using these determined values. Results No difference was observed between determined and predicted metabolizable energy values in the mixture (3,998 and 3,990 kcal/kg as-is basis, respectively). Measured standardized total tract digestible phosphorus in the mixture was less than the predicted value (4.5 vs 5.3 g/kg as-is basis, respectively; p<0.05). Measured standardized total tract digestible calcium in the mixture was greater compared with the predicted value (40.0 vs 31.7 g/kg as-is basis, respectively; p<0.05). Measured standardized ileal digestible tryptophan in the mixture was greater than the predicted value (3.7 vs 3.1 g/kg as-is basis, respectively; p<0.05) whereas other amino acid values were additive. Conclusion Energy and most of amino acid concentrations in hatchery byproducts are additive in the mixture fed to nursery pigs.
Differences in treatment effect size between progression-free survival and overall survival in anti-PD-1/PD-L1 inhibitors-based trials in advanced NSCLC: a systematic review and meta-analysis

Background To investigate the differences in treatment effect sizes between progression-free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) treated with programmed cell death 1 (PD-1) and its ligand (PD-L1) blockade-based treatments. Methods The differences in treatment effect sizes between PFS and OS were assessed by using a ratio of hazard ratio (rHR): the HR for PFS to that for OS. A random effects meta-analysis across trials was conducted to generate the combined rHR. We also evaluated the feasibility of adopting PFS as the surrogate of OS by using Spearman correlation coefficient (R) between logHRPFS and logHROS. Results A total of 27 randomized controlled trials (RCTs) with 15,590 patients were included. Treatment effect sizes were comparable, on average, for OS than for PFS (pooled rHR, 0.98; 95% CI, 0.91 to 1.08). Subgroup analysis revealed that treatment effect sizes were greater for OS than for PFS for trials with immunotherapy as second or above line treatment (rHR, 1.17; 95% CI, 1.06 to 1.29), while the differences were greater for PFS than for OS for trials with immunotherapy as first-line setting (rHR, 0.91; 95% CI, 0.84 to 0.99; Pinteraction<0.01). The coefficient of determination was 40% and R was 0.63 between logHRPFS and logHROS. Subgroup analysis showed that coefficient of determination and R were 62% and 0.79 in trials with immunotherapy as first-line setting, 22% and 0.47 in trials with immunotherapy as second or above line treatment, respectively. Discussion Treatment effect sizes between PFS and OS were roughly consistent in trials with different anti-PD-(L)1 inhibitor-based therapies. PFS could be a potential alternative endpoint for OS in trials with immunotherapy as first-line setting, but PFS should be cautiously interpreted without OS data for trials with immunotherapy as second or above line treatment.
Fact-Checking of Health Information: The Effect of Media Literacy, Metacognition and Health Information Exposure

With the rampant circulation of health information, concerns for the information quality are growing. Thereby, scholars are calling for media literacy as an educative means to cultivate fact-checking behavior among information consumers. Focusing on the critical role of metacognition for education effectiveness, this study examined the underlying mechanism that is conducive to the success of media literacy in the context of health information consumption. Based on the survey data collected from 502 Reddit.com users, our findings showed that media literacy was positively associated with fact-checking behavior for health information. Mediation analysis indicated that metacognition mediated the positive relationship between media literacy and fact-checking behavior. In addition, moderated-mediation analysis demonstrated that the mediating effect was weaker for individuals who had higher exposure to health information. The study sheds light on the factors that are essential for the success of media literacy. Implications and future directions are discussed.
Clinical outcomes of adults hospitalized for laboratory confirmed respiratory syncytial virus or influenza virus infection

Objectives Respiratory syncytial virus (RSV) can cause severe disease in adults, but far less is known than for influenza. The aim of our study was to compare the disease course of RSV infections with influenza infections among hospitalized adults. Methods We retrieved clinical data from an ongoing surveillance of adults hospitalized with RSV or influenza virus infection in two acute care hospitals in North-Eastern Switzerland during the winter seasons 2017/2018 and 2018/2019. Our main analysis compared the odds between RSV and influenza patients for admission to an intensive care unit (ICU) or in-hospital death within 7 days after admission. Results There were 548 patients, of whom 79 (14.4%) had an RSV and 469 (85.6%) an influenza virus infection. Both groups were similar with respect to age, sex, smoking status, nutritional state, and comorbidities. More RSV patients had an infiltrate on chest radiograph on admission (46.4% vs 29.9%, p = .007). The proportion of patients with RSV who died or were admitted to ICU within seven days after admission was 19.0% compared to 10.2% in influenza patients (p = .024). In multivariable analysis, a higher leukocyte count (adjusted OR 1.07, 95% CI 1.02–1.13, p = .013) and the presence of a pneumonic infiltrate (aOR 3.41, 95% CI 1.93–6.02) significantly increased the risk for experiencing the adverse primary outcome while the effect of the underlying viral pathogen became attenuated (aOR 1.18, 95% CI 0.58–2.41, p = .0.655). Conclusions Our results suggest that RSV is responsible for clinical courses at least as severe as influenza in adults. This supports the need for better guidance on diagnostic strategies as well as on preventive and therapeutic measures for hospitalized adults with RSV infection.
Changes in Influenza and Other Respiratory Virus Activity During the COVID-19 Pandemic — United States, 2020–2021

The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1-4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities.
The influence of the crowding assumptions in biofilm simulations

Microorganisms are frequently organized into crowded structures that affect the nutrients diffusion. This reduction in metabolite diffusion could modify the microbial dynamics, meaning that computational methods for studying microbial systems need accurate ways to model the crowding conditions. We previously developed a computational framework, termed CROMICS, that incorporates the effect of the (time-dependent) crowding conditions on the spatio-temporal modeling of microbial communities, and we used it to demonstrate the crowding influence on the community dynamics. To further identify scenarios where crowding should be considered in microbial modeling, we herein applied and extended CROMICS to simulate several environmental conditions that could potentially boost or dampen the crowding influence in biofilms. We explore whether the nutrient supply (rich- or low-nutrient media), the cell-packing configuration (square or hexagonal spherical cell arrangement), or the cell growing conditions (planktonic state or biofilm) modify the crowding influence on the growth of Escherichia coli. Our results indicate that the growth rate, the abundance and appearance time of different cell phenotypes as well as the amount of by-products secreted to the medium are sensitive to some extent to the local crowding conditions in all scenarios tested, except in rich-nutrient media. Crowding conditions enhance the formation of nutrient gradient in biofilms, but its effect is only appreciated when cell metabolism is controlled by the nutrient limitation. Thus, as soon as biomass (and/or any other extracellular macromolecule) accumulates in a region, and cells occupy more than 14% of the volume fraction, the crowding effect must not be underestimated, as the microbial dynamics start to deviate from the ideal/expected behaviour that assumes volumeless cells or when a homogeneous (reduced) diffusion is applied in the simulation. The modeling and simulation of the interplay between the species diversity (cell shape and metabolism) and the environmental conditions (nutrient quality, crowding conditions) can help to design effective strategies for the optimization and control of microbial systems.
Exploring brain connectivity changes in major depressive disorder using functional‐structural data fusion: A CAN‐BIND‐1 study

There is a growing interest in examining the wealth of data generated by fusing functional and structural imaging information sources. These approaches may have clinical utility in identifying disruptions in the brain networks that underlie major depressive disorder (MDD). We combined an existing software toolbox with a mathematically dense statistical method to produce a novel processing pipeline for the fast and easy implementation of data fusion analysis (FATCAT‐awFC). The novel FATCAT‐awFC pipeline was then utilized to identify connectivity (conventional functional, conventional structural and anatomically weighted functional connectivy) changes in MDD patients compared to healthy comparison participants (HC). Data were acquired from the Canadian Biomarker Integration Network for Depression (CAN‐BIND‐1) study. Large‐scale resting‐state networks were assessed. We found statistically significant anatomically‐weighted functional connectivity (awFC) group differences in the default mode network and the ventral attention network, with a modest effect size (d < 0.4). Functional and structural connectivity seemed to overlap in significance between one region‐pair within the default mode network. By combining structural and functional data, awFC served to heighten or reduce the magnitude of connectivity differences in various regions distinguishing MDD from HC. This method can help us more fully understand the interconnected nature of structural and functional connectivity as it relates to depression.
Artificial intelligence-based analysis for immunohistochemistry staining of immune checkpoints to predict resected non-small cell lung cancer survival and relapse

Background Conventional analysis of single-plex chromogenic immunohistochemistry (IHC) focused on quantitative but spatial analysis. How immune checkpoints localization related to non-small cell lung cancer (NSCLC) prognosis remained unclear. Methods Here, we analyzed ten immune checkpoints on 1,859 tumor microarrays (TMAs) from 121 NSCLC patients and recruited an external cohort of 30 NSCLC patients with 214 whole-slide IHC. EfficientUnet was applied to segment tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs), while ResNet was performed to extract prognostic features from IHC images. Results The features of galectin-9, OX40, OX40L, KIR2D, and KIR3D played an un-negatable contribution to overall survival (OS) and relapse-free survival (RFS) in the internal cohort, validated in public databases (GEPIA, HPA, and STRING). The IC-Score and Res-Score were two predictive models established by EfficientUnet and ResNet. Based on the IC-Score, Res-Score, and clinical features, the integrated score presented the highest AUC for OS and RFS, which could achieve 0.9 and 0.85 in the internal testing cohort. The robustness of Res-Score was validated in the external cohort (AUC: 0.80–0.87 for OS, and 0.83–0.94 for RFS). Additionally, the neutrophil-to-lymphocyte ratio (NLR) combined with the PD-1/PD-L1 signature established by EfficientUnet can be a predictor for RFS in the external cohort. Conclusions Overall, we established a reliable model to risk-stratify relapse and death in NSCLC with a generalization ability, which provided a convenient approach to spatial analysis of single-plex chromogenic IHC.
An association analysis between hypertension, dementia, and depression and the phases of pre-sarcopenia to sarcopenia: A cross-sectional analysis

Sarcopenia is intricately related to aging associated diseases, such as neuropsychiatric disorders, oral status, and chronic diseases. Dementia and depression are interconnected and also related to sarcopenia. The preliminary shift from robust to sarcopenia (i.e., pre-sarcopenia) is an important albeit underdiscussed stage and is the focus of this study. Identifying factors associated with pre-sarcopenia may lead to sarcopenia prevention. To separately examine the effects of dementia and depression on pre-sarcopenia/sarcopenia, we conducted multiple analyses. This cross-sectional study used health checkup data from a rural Japanese island. The participants were aged 60 years and above, and the data included muscle mass, gait speed, handgrip strength, oral status (teeth and denture), chronic diseases (e.g., hypertension), dementia (cognitive assessment for dementia, iPad Version), and depression (self-rating depression scale). A total of 753 older adult participants were divided into the sarcopenia (n = 30), pre-sarcopenia (n = 125), and robust (n = 598) groups. An ordered logit regression analysis indicated that age and depression were positively correlated with sarcopenia, while hypertension was negatively associated with it. A multiple logistic regression analysis between the robust and pre-sarcopenia groups showed significant associations between the same three variables. Depression was associated with pre-sarcopenia, but not dementia. There was also a significant association between hypertension and pre-sarcopenia. Further research is needed to reveal whether the management of these factors can prevent sarcopenia.
The importance of the ‘family clock’: women’s lived experience of fertility decision-making 6 years after attending the Fertility Assessment and Counselling Clinic

Abstract This study explored women’s lived experience of making fertility decisions six years after attending the Fertility Assessment and Counselling (FAC) clinic in Copenhagen, Denmark, which is a personalised fertility awareness intervention. We conducted a qualitative interview study with 24 women who attended the FAC clinic 6 years earlier. Interviews were semi-structured and broadly examined the women’s perceptions and experience of the intervention during follow-up. Data was analysed using a phenomenological framework and themes were identified related to women’s experience of making fertility decisions after attending the FAC clinic. The overarching theme regarding the women’s lived experience of making fertility decisions after attending the FAC clinic was: Fertility decisions were guided by the ‘family clock’. There were four themes: (i) Deciding to ‘get started’ by attending the FAC clinic; (ii) Sense of making informed and empowered decisions; (iii) Influence of partner status on fertility decisions; and (iv) Decisions dictated by circumstance over preference and knowledge. At follow-up, the majority (21 women, 88%) had become parents. More than half of the women said that they had not achieved their desired family size. Consideration of women’s ‘family clock’ is necessary in personalised fertility awareness interventions to enable women to achieve their family goals.
Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway

High malignancy and high mortality of glioma render it urgent to elucidate the underlying mechanisms of glioma carcinogenesis and explore novel targets for therapy. Epidemiologic and clinical studies have revealed that chronic stress promotes the progression of various solid tumors and is correlated with poor prognosis; however, findings reporting the involvement of chronic stress in glioma are rare. In the present study, a chronic restraint animal model and a chronic stress cell model were established to explore the effects of chronic stress on glioma and its molecular mechanisms. The results revealed that chronic stress promoted glioma growth in vivo, and the serum levels of the stress hormones glucocorticoid (GC) and noradrenaline (NE) were significantly increased. In addition, GC and NE were verified to accelerate the proliferation of glioma cells in vitro. Mechanistically, the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway was revealed to be activated under stress conditions, and inhibition of the expression of p-Akt could restrain the stress hormone-induced glioma cell proliferation. In addition, our data indicated that the GC receptor (GR) and β-adrenergic receptors (ADRBs) were both required for the biological functions of GC and NE in glioma cells. In conclusion, these results indicated that chronic stress and the stress hormones GC and NE activated PI3K/Akt signaling through binding to GR and ADRBs, thereby promoting glioma cell growth. Our findings may provide potential therapeutic targets and pave the way for the development of new strategies to protect patients with glioma from the detrimental effects of stress on tumor progression.
Myofascial Pain Syndrome Focused on the Upper Trapezius Muscle: A Comparative Randomized Controlled Trial of the Court-Type Traditional Thai Massage versus the Thai Hermit

Myofascial pain syndrome is a common problem that can develop at any age. This study compares the efficacy of the court-type traditional Thai massage (CTTM) to the Thai hermit exercise (THE) in improving the cervical range of motion (CROM) and reducing pain in the upper trapezius muscle. In this study, 46 patient subjects were randomized into 2 groups, with 1 group administered CTTM and the other administered THE. Prior to and following the experiment, their demographic characteristics, pain levels and CROM were measured using a visual analog scale (VAS) and a goniometer, respectively. Data was then analyzed using descriptive statistics, percentage, mean, and standard deviation, as well as inferential statistics. The findings indicate that subjects in both groups demonstrated significantly lower pain and significantly better CROM (P < 0.05). In terms of comparative treatment between the CTTM and THE groups, the results were not found to differ in the range of motion, but a clear difference in pain level measured by VAS was found, in which CTTM provides a better way of reducing pain at the trigger point than THE (P < 0.05). From the findings, it can be concluded that both CTTM and THE are comparably efficacious therapies for myofascial pain in the upper trapezius muscle.
Replenishment of TCA cycle intermediates provides photoreceptor resilience against neurodegeneration during progression of retinitis pigmentosa

The metabolic environment is important for neuronal cells, such as photoreceptors. When photoreceptors undergo degeneration, as occurs during retinitis pigmentosa (RP), patients have progressive loss of vision that proceeds to full blindness. Currently, there are no available treatments for the majority of RP diseases. We performed metabolic profiling of the neural retina in a preclinical model of RP and found that TCA cycle intermediates were reduced during disease. We then determined that (a) promoting citrate production within the TCA cycle in retinal neurons during disease progression protected the photoreceptors from cell death and prolonged visual function, (b) supplementation with single metabolites within the TCA cycle provided this therapeutic effect in vivo over time, and (c) this therapeutic effect was not specific to a particular genetic mutation but had broad applicability for patients with RP and other retinal degenerative diseases. Overall, targeting TCA cycle activity in the neural retina promoted photoreceptor survival and visual function during neurodegenerative disease.