Miracle-dz/UniFAR-FTUs huggingface dataset:
Developing an Intervention and Evaluation Model of Outdoor Therapy for Employee Burnout: Unraveling the Interplay Between Context, Processes, and Outcomes

Background Burnout is a major societal issue adversely affecting employees’ health and performance, which over time results in high sick leave costs for organizations. Traditional rehabilitation therapies show suboptimal effects on reducing burnout and the return-to-work process. Based on the health-promoting effects of nature, taking clients outdoors into nature is increasingly being used as a complementary approach to traditional therapies, and evidence of their effectiveness is growing. Theories explaining how the combination of general psychological support and outdoor-specific elements can trigger the rehabilitation process in outdoor therapy are often lacking, however, impeding its systematic research. Aim The study aims to develop an intervention and evaluation model for outdoor therapy to understand and empirically evaluate whether and how such an outdoor intervention may work for rehabilitation after burnout. Methodological Approach We build on the exemplary case of an outdoor intervention for rehabilitation after burnout, developed by outdoor clinical psychologists in Netherlands. We combined the generic context, process, and outcome evaluation model and the burnout recovery model as an overarching deductive frame. We then inductively specified the intervention and evaluation model of outdoor therapy, building on the following qualitative data: semi-structured interviews with outdoor clinical psychologists and former clients; a content analysis of the intervention protocol; and reflective meetings with the intervention developers and health promotion experts. Results We identified six key outdoor intervention elements: (1) physical activity; (2) reconnecting body and mind; (3) nature metaphors; (4) creating relationships; (5) observing natural interactions; and (6) experiential learning. The results further showed that the implementation of these elements may facilitate the rehabilitation process after burnout in which proximal, intermediate, and distal outcomes emerge. Finally, the results suggested that this implementation process depends on the context of the therapist (e.g., number of clients per day), therapy (e.g., privacy issues), and of the clients (e.g., affinity to nature). Conclusion The intervention and evaluation model for outdoor therapy shows how key outdoor intervention elements may contribute to the rehabilitation process after burnout. However, our model needs to be further tested among a larger group of clients to empirically evaluate whether and how outdoor therapy can support rehabilitation.
Integrated Analysis of Transcriptomic and Genomic Data Reveals Blood Biomarkers With Diagnostic and Prognostic Potential in Non-small Cell Lung Cancer

Background: Lung cancer is the second most common cancer and the main leading cause of cancer-associated death worldwide. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer diagnoses and more than 50% of all lung cancer cases are diagnosed at an advanced stage; hence have poor prognosis. Therefore, it is important to diagnose NSCLC patients reliably and as early as possible in order to reduce the risk of mortality. Methods: We identified blood-based gene markers for early NSCLC by performing a multi-omics approach utilizing integrated analysis of global gene expression and copy number alterations of NSCLC patients using array-based techniques. We also validated the diagnostic and the prognostic potential of the gene signature using independent datasets with detailed clinical information. Results: We identified 12 genes that are significantly expressed in NSCLC patients’ blood, at the earliest stages of the disease, and associated with a poor disease outcome. We then validated 12-gene signature’s diagnostic and prognostic value using independent datasets of gene expression profiling of over 1000 NSCLC patients. Indeed, 12-gene signature predicted disease outcome independently of other clinical factors in multivariate regression analysis (HR = 2.64, 95% CI = 1.72–4.07; p = 1.3 × 10−8). Significantly altered functions, pathways, and gene networks revealed alterations in several key genes and cancer-related pathways that may have importance for NSCLC transformation, including FAM83A, ZNF696, UBE2C, RECK, TIMM50, GEMIN7, and XPO5. Conclusion: Our findings suggest that integrated genomic and network analyses may provide a reliable approach to identify genes that are associated with NSCLC, and lead to improved diagnosis detecting the disease in early stages in patients’ blood instead of using invasive techniques and also have prognostic potential for discriminating high-risk patients from the low-risk ones.
Plant Growth-Promoting Activity of Bacillus sp. PG-8 Isolated From Fermented Panchagavya and Its Effect on the Growth of Arachis hypogea

A natural bacterial isolate that shows multiple plant growth-promoting activities was isolated from fermented panchagavya (a mixture of five indigenous cow products). It is a gram-positive, endospore-forming bacteria identified as Bacillus sp. PG-8 by 16S rRNA gene sequencing. The Bacillus sp. PG-8 have shown multiple plant growth-promoting activities as indole acetic acid (2.78 μg/ml), gibberellic acid (0.7 mg/ml), ammonia (6.51 μmol/ml), exopolysaccharide (2.6% w/v) production, and phosphate solubilization (198.27 μg/ml). The Bacillus sp. PG-8 has ability to survive under the abiotic stress conditions such as temperature (28–46°C), pH (5.0–12.0), salt (0.5–20.0% w/v NaCl), and osmotic resistance (1–10% w/v PEG-6000). Due to its diverse characteristics, the effect of Bacillus sp. PG-8 was tested on Arachis hypogea (groundnut). The seeds treated with Bacillus sp. PG-8 demonstrated a 70% germination rate with seedling vigor indexes of 154. In pot study, Arachis hypogea growth showed 1.38, 1.38, 1.32, 1.39, and 1.52 times increase in root hair number, leaf numbers, leaf width, leaf length, and leaf area, respectively. The addition of Bacillus sp. PG-8 culture to the Arachis hypogea plant resulted in a significant improvement in plant growth. Bacillus sp. PG-8 is a spore producer with stress tolerance and multiple plant growth-promoting properties, which makes it a potential liquid biofertilizer candidate.
Intake of Soy, Soy Isoflavones and Soy Protein and Risk of Cancer Incidence and Mortality

Background and Aims Associations between soy intake and risk of cancer have been evaluated in prospective observational studies with inconsistent results. Whether the potential anticancer effects offered by soy were attributed to soy isoflavones and soy protein still needs to be elucidated. This study aimed to comprehensively quantify the association of soy, soy isoflavones and soy protein intake with risk of cancer incidence and cancer mortality by conducting a meta-analysis of all available studies. Methods PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to 16 September 2021. Prospective cohort studies that examined the effect of soy, soy isoflavones and soy protein on cancer incidence and cancer mortality were identified. Random-effects models were used to pool the multivariable-adjusted relative risks (RRs) and corresponding 95% confidence intervals (CIs). The potential dose-response relations were explored by using generalized least-squares trend estimation. Results Eighty one prospective cohort studies were included in the meta-analysis. A higher intake of soy was significantly associated with a 10% reduced risk of cancer incidence (RR, 0.90; 95% CI, 0.83–0.96). Each additional 25 g/d soy intake decreased the risk of cancer incidence by 4%. Intake of soy isoflavones was inversely associated with risk of cancer incidence (RR, 0.94; 95% CI, 0.89–0.99), whereas no significant association was observed for soy protein. The risk of cancer incidence was reduced by 4% with each 10 mg/d increment of soy isoflavones intake. Similar inverse associations were also found for soy in relation to site-specific cancers, particularly lung cancer (RR, 0.67; 95%CI, 0.52–0.86) and prostate cancer (RR, 0.88; 95%CI, 0.78–0.99). However, high intake of soy, soy isoflavones and soy protein were not associated with cancer mortality. Conclusions Higher intake of soy and soy isoflavones were inversely associated with risk of cancer incidence, which suggested that the beneficial role of soy against cancer might be primarily attributed to soy isoflavones. These findings support recommendations to include soy as part of a healthy dietary pattern for the prevention of cancer.
Drug-Related Lymphedema: Mysteries, Mechanisms, and Potential Therapies

The lymphatic circulation is an important component of the circulatory system in humans, playing a critical role in the transport of lymph fluid containing proteins, white blood cells, and lipids from the interstitial space to the central venous circulation. The efficient transport of lymph fluid critically relies on the rhythmic contractions of collecting lymph vessels, which function to “pump” fluid in the distal to proximal direction through the lymphatic circulation with backflow prevented by the presence of valves. When rhythmic contractions are disrupted or valves are incompetent, the loss of lymph flow results in fluid accumulation in the interstitial space and the development of lymphedema. There is growing recognition that many pharmacological agents modify the activity of ion channels and other protein structures in lymph muscle cells to disrupt the cyclic contraction and relaxation of lymph vessels, thereby compromising lymph flow and predisposing to the development of lymphedema. The effects of different medications on lymph flow can be understood by appreciating the intricate intracellular calcium signaling that underlies the contraction and relaxation cycle of collecting lymph vessels. For example, voltage-sensitive calcium influx through long-lasting (“L-type”) calcium channels mediates the rise in cytosolic calcium concentration that triggers lymph vessel contraction. Accordingly, calcium channel antagonists that are mainstay cardiovascular medications, attenuate the cyclic influx of calcium through L-type calcium channels in lymph muscle cells, thereby disrupting rhythmic contractions and compromising lymph flow. Many other classes of medications also may contribute to the formation of lymphedema by impairing lymph flow as an off-target effect. The purpose of this review is to evaluate the evidence regarding potential mechanisms of drug-related lymphedema with an emphasis on common medications administered to treat cardiovascular diseases, metabolic disorders, and cancer. Additionally, although current pharmacological approaches used to alleviate lymphedema are largely ineffective, efforts are mounting to arrive at a deeper understanding of mechanisms that regulate lymph flow as a strategy to identify novel anti-lymphedema medications. Accordingly, this review also will provide information on studies that have explored possible anti-lymphedema therapeutics.
Early Health Economic Modeling of Novel Therapeutics in Age-Related Hearing Loss

Background Health systems face challenges to accelerate access to innovations that add value and avoid those unlikely to do so. This is very timely to the field of age-related sensorineural hearing loss (ARHL), where a significant unmet market need has been identified and sizeable investments made to promote the development of novel hearing therapeutics (NT). This study aims to apply health economic modeling to inform the development of cost-effective NT. Methods We developed a decision-analytic model to assess the potential costs and effects of using regenerative NT in patients ≥50 with ARHL. This was compared to the current standard of care including hearing aids and cochlear implants. Input data was collected from systematic literature searches and expert opinion. A UK NHS healthcare perspective was adopted. Three different but related analyses were performed using probabilistic modeling: (1) headroom analysis, (2) scenario analyses, and (3) threshold analyses. Results The headroom analysis shows an incremental net monetary benefit (iNMB) of £20,017[£11,299–£28,737] compared to the standard of care due to quality-adjusted life-years (QALY) gains and cost savings. Higher therapeutic efficacy and access for patients with all degrees of hearing loss yields higher iNMBs. Threshold analyses shows that the ceiling price of the therapeutic increases with more severe degrees of hearing loss. Conclusion NT for ARHL are potentially cost-effective under current willingness-to-pay (WTP) thresholds with considerable room for improvement in the current standard of care pathway. Our model can be used to help decision makers decide which therapeutics represent value for money and are worth commissioning, thereby paving the way for urgently needed NT.
Comparative Transcriptome Analysis Unravels Defense Pathways of Fraxinus velutina Torr Against Salt Stress

Fraxinus velutina Torr with high salt tolerance has been widely grown in saline lands in the Yellow River Delta, China. However, the salt-tolerant mechanisms of F. velutina remain largely elusive. Here, we identified two contrasting cutting clones of F. velutina, R7 (salt-tolerant), and S4 (salt-sensitive) by measuring chlorophyll fluorescence characteristics (Fv/Fm ratio) in the excised leaves and physiological indexes in roots or leaves under salt treatment. To further explore the salt resistance mechanisms, we compared the transcriptomes of R7 and S4 from leaf and root tissues exposed to salt stress. The results showed that when the excised leaves of S4 and R7 were, respectively, exposed to 250 mM NaCl for 48 h, Fv/Fm ratio decreased significantly in S4 compared with R7, confirming that R7 is more tolerant to salt stress. Comparative transcriptome analysis showed that salt stress induced the significant upregulation of stress-responsive genes in R7, making important contributions to the high salt tolerance. Specifically, in the R7 leaves, salt stress markedly upregulated key genes involved in plant hormone signaling and mitogen-activated protein kinase signaling pathways; in the R7 roots, salt stress induced the upregulation of main genes involved in proline biosynthesis and starch and sucrose metabolism. In addition, 12 genes encoding antioxidant enzyme peroxidase were all significantly upregulated in both leaves and roots. Collectively, our findings revealed the crucial defense pathways underlying high salt tolerance of R7 through significant upregulation of some key genes involving metabolism and hub signaling pathways, thus providing novel insights into salt-tolerant F. velutina breeding.
Adherence to the Chinese Food Pagoda in the High-Risk Population of Non-communicable Diseases Aged 35–59 in Central China

Objectives A healthy dietary habit is essential for preventing non-communicable diseases (NCDs). We aimed to assess the adherence to the Chinese Food Pagoda (CFP) proposed in the Chinese Dietary Guidelines 2016 in the high-risk population of NCDs in central China. Methods A cross-sectional study was conducted in two large enterprises (totally 3,016 employees) from October to December 2019 in Hubei Province (central China). The high-risk population of NCDs was identified by physical examination, laboratory test and face-to-face questionnaire survey according to the National Norms for Prevention and Control of Non-communicable Diseases issued by the Chinese government. We assessed the deviation of real diet from the CFP recommended diet in the high-risk population of NCDs. Results A total of 821 participants aged 35–59 years old with at least one high-risk factor of NCDs were enrolled in our study. Of them, 53.8% were daily smokers, 49.6% had elevated blood cholesterol, 31.4% were centrally obese, 23.3% had high normal blood pressure, and 3.5% had impaired fasting glucose. Significant disparity was detected in the high-risk population of NCDs between real food consumption and the CFP's recommendation (P < 0.05), such as the deficient intake of nuts and milk and dairy products, and the over-consumption of cereals, meat and poultry, oil, and salt. Participants with impaired fasting glucose had the highest intake of cereals and vegetables on average. Participants with central obesity were more likely to consume meat and poultry (P < 0.05). The lowest average intake of eggs and the highest average intake of milk and dairy products were found in participants with high blood cholesterol (P < 0.05). The daily smokers were more likely to consume beans and nuts (P < 0.05). The lowest average intake of fruits and the highest average intake of tubers were found in participants with high normal blood pressure (P < 0.05). Conclusion Adherence to CFP in the high-risk population of NCDs appeared to be challenging. It is necessary to adopt dietary education campaign focusing on the high-risk population of NCDs to prevent or delay the occurrence of NCDs.
Don’t Be Fooled by Randomness: Valid p-Values for Single Molecule Microscopy

The human mind shows extraordinary capability at recognizing patterns, while at the same time tending to underestimate the natural scope of random processes. Taken together, this easily misleads researchers in judging whether the observed characteristics of their data are of significance or just the outcome of random effects. One of the best tools to assess whether observed features fall into the scope of pure randomness is statistical significance testing, which quantifies the probability to falsely reject a chosen null hypothesis. The central parameter in this context is the p-value, which can be calculated from the recorded data sets. In case of p-values smaller than the level of significance, the null hypothesis is rejected, otherwise not. While significance testing has found widespread application in many sciences including the life sciences, it is hardly used in (bio-)physics. We propose here that significance testing provides an important and valid addendum to the toolbox of quantitative (single molecule) biology. It allows to support a quantitative judgement (the hypothesis) about the data set with a probabilistic assessment. In this manuscript we describe ways for obtaining valid p-values in two selected applications of single molecule microscopy: (i) Nanoclustering in single molecule localization microscopy. Previously, we developed a method termed 2-CLASTA, which allows to calculate a valid p-value for the null hypothesis of an underlying random distribution of molecules of interest while circumventing overcounting issues. Here, we present an extension to this approach, yielding a single overall p-value for data pooled from multiple cells or experiments. (ii) Single molecule trajectories. Data from a single molecule trajectory are inherently correlated, thus prohibiting a direct analysis via conventional statistical tools. Here, we introduce a block permutation test, which yields a valid p-value for the analysis and comparison of single molecule trajectory data. We exemplify the approach based on FRET trajectories.
Pyroptosis-Related lncRNAs for Predicting the Prognosis and Identifying Immune Microenvironment Infiltration in Breast Cancer Lung Metastasis

Breast cancer (BC) is the second leading cause of death among women and is highly heterogeneous. Three pyroptosis (PR) subtypes were identified in patients with BC from the Cancer Genome Atlas Database (TCGA) cohorts using 20 PR-related regulators, which illustrate a strong association between BC prognosis and PR. Lung metastasis commonly occurs in the advanced stages of BC, resulting in a poor quality of life. Eight differentially expressed (DE) lncRNAs were identified using LASSO–Cox analysis between PR-related and BC lung metastasis. Moreover, a BRCA risk-score (RS) model was established using multivariate Cox regression, which correlated with prognosis in TCGA-BRCA. Clinical characteristics, tumor mutation burden, and tumor immune cell infiltration were extensively investigated between high- and low-RS groups. Similarly, a lower RS implied longer overall survival, greater inflammatory cell infiltration, and better immunotherapeutic response to PD-1 blockers. Our findings provide a foundation for future studies targeting PR and confirme that RS could predict the prognosis of patients with BC.
Genome-Wide Transcriptional Response of Mycobacterium smegmatis MC2155 to G-Quadruplex Ligands BRACO-19 and TMPyP4

G-quadruplexes (G4s) are non-canonical DNA structures that could be considered as potential therapeutic targets for antimicrobial compounds, also known as G4-stabilizing ligands. While some of these ligands are shown in vitro to have a stabilizing effect, the precise mechanism of antibacterial action has not been fully investigated. Here, we employed genome-wide RNA-sequencing to analyze the response of Mycobacterium smegmatis to inhibitory concentrations of BRACO-19 and TMPyP4 G4 ligands. The expression profile changed (FDR < 0.05, log2FC > |1|) for 822 (515↑; 307↓) genes in M. smegmatis in response to BRACO-19 and for 680 (339↑; 341↓) genes in response to TMPyP4. However, the analysis revealed no significant ligand-induced changes in the expression levels of G4-harboring genes, genes under G4-harboring promoters, or intergenic regions located on mRNA-like or template strands. Meanwhile, for the BRACO-19 ligand, we found significant changes in the replication and repair system genes, as well as in iron metabolism genes which is, undoubtedly, evidence of the induced stress. For the TMPyP4 compound, substantial changes were found in transcription factors and the arginine biosynthesis system, which may indicate multiple biological targets for this compound.
Modelling of VSC Converters in the Rotating dq Frame for DC Fault

As the future DC grids will involve numerous converter systems, the accuracy and speed of their modeling becomes of high importance. The modelling in a rotating dq frame is able to transform the quantities from ac variables to dc variables resulting in a significantly improved simulation speed. dq modelling is normally used for VSC converter in dynamic studies, while dc fault study is typically studied separately in static abc frame. This creates problems if converters are studied for transient DC faults. Commonly, the diode bridge is assumed to be a current source converter which gives inaccurate results for a diode bridge which is a part of VSC converter. To solve these challenges, a new modelling method for modelling VSC converter in the rotating frame for dc fault study is proposed. A unified modelling of the VSC converter for both dynamic and dc fault study is then further developed. Simulation results verified that the proposed model is accurate compared with detailed switching model. The proposed model is able to replace the detailed switching model and conventional dq frame model for both dc fault and dynamic study. A new modelling platform in the dq frame could be further developed employing the method proposed in this paper.