Miracle-dz/UniFAR-FTUs huggingface dataset:
On the Relationship Between Pain Variability and Relief in Randomized Clinical Trials

Previous research reports suggest greater baseline variability is associated with greater pain relief in those who receive a placebo. However, studies that evidence this association do not control for confounding effects from regression to the mean and natural history. In this report, we analyzed data from two randomized clinical trials (Placebo I and Placebo II, total N = 139) while adjusting for the effects of natural history and regression to the mean via a no treatment group. Results agree between the two placebo groups in each study: both placebo groups showed negligible semi-partial correlations between baseline variability and adjusted response [rsp (CI95%) = 0.22 (0.03, 0.42) and 0 (−0.07, 0.07) for Placebo I and II, respectively]. The no treatment group in Placebo I showed a negative correlation [−0.22 (−0.43, −0.02)], but the no treatment and drug groups in Placebo II's correlations were negligible [−0.02 (−0.08, 0.02) and 0.00 (−0.10, 0.12) for the no treatment and drug groups, respectively]. When modeled as a linear covariate, baseline pain variability accounted for <1% of the variance in post-intervention pain across both studies. Even after adjusting for baseline pain and natural history, the inability of baseline pain variability to account for substantial variance in pain response highlights that previous results concerning pain variability and treatment response may be inconsistent. Indeed, the relationship appears to be neither consistently specific nor sensitive to improvements in the placebo group. More work is needed to understand and establish the prognostic value of baseline pain variability—especially its placebo specificity and generalizability across patient populations.
Transcriptomic Analysis of Resistant and Wild-Type Isolates Revealed Fludioxonil as a Candidate for Controlling the Emerging Isoprothiolane Resistant Populations of Magnaporthe oryzae

The point mutation R343W in MoIRR, a putative Zn2Cys6 transcription factor, introduces isoprothiolane (IPT) resistance in Magnaporthe oryzae. However, the function of MoIRR has not been characterized. In this study, the function of MoIRR was investigated by subcellular localization observation, transcriptional autoactivation test, and transcriptomic analysis. As expected, GFP-tagged MoIRR was translocated in the nucleus, and its C-terminal could autonomously activate the expression of reporter genes HIS3 and α-galactosidase in absence of any prey proteins in Y2HGold, suggesting that MoIRR was a typical transcription factor. Transcriptomic analysis was then performed for resistant mutant 1a_mut (R343W), knockout transformant ΔMoIRR-1, and their parental wild-type isolate H08-1a. Upregulated genes in both 1a_mut and ΔMoIRR-1 were involved in fungicide resistance-related KEGG pathways, including the glycerophospholipid metabolism and Hog1 MAPK pathways. All MoIRR deficiency-related IPT-resistant strains exhibited increased susceptibility to fludioxonil (FLU) that was due to the upregulation of Hog1 MAPK pathway genes. The results indicated a correlation between FLU susceptibility and MoIRR deficiency-related IPT resistance in M. oryzae. Thus, using a mixture of IPT and FLU could be a strategy to manage the IPT-resistant populations of M. oryzae in rice fields.
EASIX and Severe Endothelial Complications After CD19-Directed CAR-T Cell Therapy—A Cohort Study

Background Endothelial dysfunction is associated with two main complications of chimeric antigen receptor T (CAR-T) cell therapy, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). This study evaluates the Endothelial Activation and Stress Index (EASIX) as a prognostic marker for high-grade CRS and ICANS in patients treated with CD19-directed CAR-T cells. Methods In this retrospective study, a training cohort of 93 patients from the ZUMA-1 trial and a validation cohort of 121 patients from two independent centers (University Hospital Heidelberg, Charité University Medicine Berlin) were investigated. The primary objective was to assess the predictive capacity of EASIX measured immediately before the start of lymphodepletion (EASIX-pre) for the occurrence of grade ≥3 CRS and/or ICANS. To explore a possible endothelial link, serum levels of endothelial stress markers (angiopoietin-2, suppressor of tumorigenicity-2, soluble thrombomodulin, and interleukin-8) were determined before lymphodepletion and on day 7 after CART infusion in the validation cohort (n = 47). Results The prognostic effect of EASIX-pre on grade ≥3 CRS and/or ICANS was significant in the training cohort [OR 2-fold increase 1.72 (1.26–2.46)] and validated in the independent cohort. An EASIX-pre cutoff >4.67 derived from the training cohort associated with a 4.3-fold increased odds ratio of severe CRS/ICANS in the independent cohort. Serum endothelial distress markers measured on day+7 correlated with EASIX-pre and associated with severe complications. Conclusions EASIX-pre is a powerful predictor of severe CRS/ICANS after CD19-directed CART therapy and might be used as a basis for risk-adapted prevention strategies.
Understanding Why Tourists Who Share Travel Photos Online Give More Positive Tourism Product Evaluation: Evidence From Chinese Tourists

This study tested a conceptual model in which photo-sharing behavior during travel elicits tourists’ emotional state, and in turn improves evaluation of the tourism product. The research results in the context of tourist attractions and restaurants provide support for the proposed model. Specifically, tourists’ photo-sharing behavior was significantly associated with more positive product evaluation, both directly and indirectly via the emotion of pleasure. These associations were stronger when the interdependent self-construers had good social experience. The results provide practical guidance for marketers to developing marketing strategy.
Updated Review of the Evidence Supporting the Medical and Legal Use of NeuroQuant® and NeuroGage® in Patients With Traumatic Brain Injury

Over 40 years of research have shown that traumatic brain injury affects brain volume. However, technical and practical limitations made it difficult to detect brain volume abnormalities in patients suffering from chronic effects of mild or moderate traumatic brain injury. This situation improved in 2006 with the FDA clearance of NeuroQuant®, a commercially available, computer-automated software program for measuring MRI brain volume in human subjects. More recent strides were made with the introduction of NeuroGage®, commercially available software that is based on NeuroQuant® and extends its utility in several ways. Studies using these and similar methods have found that most patients with chronic mild or moderate traumatic brain injury have brain volume abnormalities, and several of these studies found—surprisingly—more abnormal enlargement than atrophy. More generally, 102 peer-reviewed studies have supported the reliability and validity of NeuroQuant® and NeuroGage®. Furthermore, this updated version of a previous review addresses whether NeuroQuant® and NeuroGage® meet the Daubert standard for admissibility in court. It concludes that NeuroQuant® and NeuroGage® meet the Daubert standard based on their reliability, validity, and objectivity. Due to the improvements in technology over the years, these brain volumetric techniques are practical and readily available for clinical or forensic use, and thus they are important tools for detecting signs of brain injury.
Influence of Renin-Angiotensin System Inhibitors on Postoperative Delirium in Patients With Pulmonary Arterial Hypertension: A Secondary Analysis of a Retrospective Cohort Study

Objective To investigate the correlation between preoperative use of ACEIs/ARBs and postoperative delirium (POD) in surgical patients with pulmonary arterial hypertension (PAH). Methods The present study is a secondary analysis of a retrospective cohort study conducted at the University of Washington Medical Center from April 2007 to September 2013. Patients with PAH who underwent non-cardiac, non-obstetric surgery were enrolled in the original research. We further excluded stroke, sepsis, and craniotomy patients from interfering with POD evaluation. The univariate regression analysis and multivariate-adjusted model were used to explore the influence of preoperative ACEIs/ARBs use on the occurrence of POD. Results A total of 539 patients were included in this study. The incidence of POD in these patients was 3.0%. Following the adjustment of potential confounders (age, BMI, smoking status, pulmonary arterial systolic pressure, length of surgery, vascular surgery, asthma, obstructive sleep apnea, renal failure, atrial fibrillation, coronary artery disease, hydrochlorothiazide, alpha-blocker, calcium channel blocker, antiplatelet, steroids, statin, isoflurane), a negative relationship was found between preoperative use of ACEIs/ARBs and occurrence of POD (OR = 0.15, 95%CI: 0.03 to 0.80, P = 0.0266). Conclusion Preoperative use of ACEIs/ARBs in patients with PAH reduces the risk of POD. ACEIs/ARBs may be more recommended for patients with PAH in the future.
The Interactive Model of L2 Listening Processing in Chinese Bilinguals: A Multiple Mediation Analysis

Second language (L2) listening is a common challenge for language learners. It remains largely unknown how bilinguals process L2 listening. The literature has suggested an interactive model of L2 listening processing. However, few studies have examined the model from an experimental approach. The current study tried to provide empirical evidence for the interactive model of L2 listening processing in bilinguals by exploring the relationships among English spoken word segmentation (SWS), cognitive inhibition, cognitive flexibility, and L2 listening proficiency. The results showed positive associations among SWS, cognitive inhibition, cognitive flexibility, and L2 listening proficiency. Mediation analysis suggested that SWS might have a positive influence on L2 listening proficiency both directly and indirectly through cognitive inhibition and cognitive flexibility, respectively. These results imply that both bottom-up (reflected at SWS) and top-down (reflected at cognitive inhibition and flexibility) processes are engaged in bilinguals’ L2 listening processing.
Epigenetics in Ecology, Evolution, and Conservation

Epigenetic variation is often characterized by modifications to DNA that do not alter the underlying nucleotide sequence, but can influence behavior, morphology, and physiological phenotypes by affecting gene expression and protein synthesis. In this review, we consider how the emerging field of ecological epigenetics (eco-epi) aims to use epigenetic variation to explain ecologically relevant phenotypic variation and predict evolutionary trajectories that are important in conservation. Here, we focus on how epigenetic data have contributed to our understanding of wild populations, including plants, animals, and fungi. First, we identified published eco-epi literature and found that there was limited taxonomic and ecosystem coverage and that, by necessity of available technology, these studies have most often focused on the summarized epigenome rather than locus- or nucleotide-level epigenome characteristics. We also found that while many studies focused on adaptation and heritability of the epigenome, the field has thematically expanded into topics such as disease ecology and epigenome-based ageing of individuals. In the second part of our synthesis, we discuss key insights that have emerged from the epigenetic field broadly and use these to preview the path toward integration of epigenetics into ecology. Specifically, we suggest moving focus to nucleotide-level differences in the epigenome rather than whole-epigenome data and that we incorporate several facets of epigenome characterization (e.g., methylation, chromatin structure). Finally, we also suggest that incorporation of behavior and stress data will be critical to the process of fully integrating eco-epi data into ecology, conservation, and evolutionary biology.
Management of Long-Term Sores and Ulcers of Breast Cancer Survivors With Chinese Herbal Medicines: A Case Report

Background The treatment of long-term sores and ulcers of breast cancer metastatic recurrence is a serious challenge with successful cases rarely being documented. Herein we reported a successful case using the internal vitality supporting method of Chinese herbal medicine (CHM). Case Summary A 59-year-old female Chinese patient, 10 years after breast cancer surgery, developed metastatic lesions in the lung. Thereafter she received radiofrequency ablation and adjuvant treatments for 1 year with severe sequelae, a right unhealed sore and ulcer. She became frustrated and depressive. And subsequently sought exclusive treatment under the guidance of a Traditional Chinese Medicine (TCM) physician. The patient's condition was categorized as a Qi (or vitality) deficiency-related sore and ulcer. In the next six months, the patient still follows a traditional Chinese medicine therapeutic regimen based on the internal vitality supporting method of Chinese herbs. Conclusion The sore and ulcer from the surgical wound were healed. Up to now, the tumor markers have remained stable. TCM personalized survivorship treatment and psychosocial support can help patients improve their quality of life after acute treatment and in the long-term for cancer survivors.
Transcriptomics and Metabolomics Identify Drug Resistance of Dormant Cell in Colorectal Cancer

Background: Tumor dormancy is an important way to develop drug resistance. This study aimed to identify the characteristics of colorectal cancer (CRC) cell dormancy. Methods: Based on the CRC cohorts, a total of 1,044 CRC patients were included in this study, and divided into a dormant subgroup and proliferous subgroup. Non-negative matrix factorization (NMF) was used to distinguish the dormant subgroup of CRC via transcriptome data of cancer tissues. Gene Set Enrichment Analysis (GSEA) was used to explore the characteristics of dormant CRC. The characteristics were verified in the cell model, which was used to predict key factors driving CRC dormancy. Potential treatments for CRC dormancy were also examined. Results: The dormant subgroup had a poor prognosis and was more likely to relapse. GSEA analysis showed two defining characteristics of the dormant subgroup, a difference in energy metabolism and synergistic effects of cancer-associated fibroblasts (CAFs), which were verified in a dormant cell model. Transcriptome and clinical data identified LMOD1, MAB21L2, and ASPN as important factors associated with cell dormancy and verified that erlotinib, and CB-839 were potential treatment options. Conclusion: Dormant CRC is associated with high glutamine metabolism and synergizes with CAFs in 5-FU resistance, and the key effectors are LMOD1, MAB21L2, and ASPN. Austocystin D, erlotinib, and CB-839 may be useful for dormant CRC.
Long-Term Stability of Bacterial Associations in a Microcosm of Ostreococcus tauri (Chlorophyta, Mamiellophyceae)

Phytoplankton–bacteria interactions rule over carbon fixation in the sunlit ocean, yet only a handful of phytoplanktonic–bacteria interactions have been experimentally characterized. In this study, we investigated the effect of three bacterial strains isolated from a long-term microcosm experiment with one Ostreococcus strain (Chlorophyta, Mamiellophyceae). We provided evidence that two Roseovarius strains (Alphaproteobacteria) had a beneficial effect on the long-term survival of the microalgae whereas one Winogradskyella strain (Flavobacteriia) led to the collapse of the microalga culture. Co-cultivation of the beneficial and the antagonistic strains also led to the loss of the microalga cells. Metagenomic analysis of the microcosm is consistent with vitamin B12 synthesis by the Roseovarius strains and unveiled two additional species affiliated to Balneola (Balneolia) and Muricauda (Flavobacteriia), which represent less than 4% of the reads, whereas Roseovarius and Winogradskyella recruit 57 and 39% of the reads, respectively. These results suggest that the low-frequency bacterial species may antagonize the algicidal effect of Winogradskyella in the microbiome of Ostreococcus tauri and thus stabilize the microalga persistence in the microcosm. Altogether, these results open novel perspectives into long-term stability of phytoplankton cultures.
Rapid Discrimination of Clinically Important Pathogens Through Machine Learning Analysis of Surface Enhanced Raman Spectra

With its low-cost, label-free and non-destructive features, Raman spectroscopy is becoming an attractive technique with high potential to discriminate the causative agent of bacterial infections and bacterial infections per se. However, it is challenging to achieve consistency and accuracy of Raman spectra from numerous bacterial species and phenotypes, which significantly hinders the practical application of the technique. In this study, we analyzed surfaced enhanced Raman spectra (SERS) through machine learning algorithms in order to discriminate bacterial pathogens quickly and accurately. Two unsupervised machine learning methods, K-means Clustering (K-Means) and Agglomerative Nesting (AGNES) were performed for clustering analysis. In addition, eight supervised machine learning methods were compared in terms of bacterial predictions via Raman spectra, which showed that convolutional neural network (CNN) achieved the best prediction accuracy (99.86%) with the highest area (0.9996) under receiver operating characteristic curve (ROC). In sum, machine learning methods can be potentially applied to classify and predict bacterial pathogens via Raman spectra at general level. Graphical Abstract
Modulation of Cellular Function by the Urokinase Receptor Signalling: A Mechanistic View

Urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycosyl-phosphatidyl-inositol anchored (GPI) membrane protein. The uPAR primary ligand is the serine protease urokinase (uPA), converting plasminogen into plasmin, a broad spectrum protease, active on most extracellular matrix components. Besides uPA, the uPAR binds specifically also to the matrix protein vitronectin and, therefore, is regarded also as an adhesion receptor. Complex formation of the uPAR with diverse transmembrane proteins, including integrins, formyl peptide receptors, G protein-coupled receptors and epidermal growth factor receptor results in intracellular signalling. Thus, the uPAR is a multifunctional receptor coordinating surface-associated pericellular proteolysis and signal transduction, thereby affecting physiological and pathological mechanisms. The uPAR-initiated signalling leads to remarkable cellular effects, that include increased cell migration, adhesion, survival, proliferation and invasion. Although this is beyond the scope of this review, the uPA/uPAR system is of great interest to cancer research, as it is associated to aggressive cancers and poor patient survival. Increasing evidence links the uPA/uPAR axis to epithelial to mesenchymal transition, a highly dynamic process, by which epithelial cells can convert into a mesenchymal phenotype. Furthermore, many reports indicate that the uPAR is involved in the maintenance of the stem-like phenotype and in the differentiation process of different cell types. Moreover, the levels of anchor-less, soluble form of uPAR, respond to a variety of inflammatory stimuli, including tumorigenesis and viral infections. Finally, the role of uPAR in virus infection has received increasing attention, in view of the Covid-19 pandemics and new information is becoming available. In this review, we provide a mechanistic perspective, via the detailed examination of consolidated and recent studies on the cellular responses to the multiple uPAR activities.
Reciprocal Relationships Between Problematic Social Media Use, Problematic Gaming, and Psychological Distress Among University Students: A 9-Month Longitudinal Study

Background The causal relationships between two specific types of problematic use in internet-related activities [i.e., problematic social media use (PSMU) and problematic gaming (PG)] and psychological distress remain controversial. The present study investigated the temporal relationships between PSMU, PG, and psychological distress (i.e., anxiety, depression) in university students. Methods Hong Kong and Taiwan university students [N = 645; nmale = 266; mean = 20.95 years (SD = 5.63)] were recruited for a survey study, with follow-ups at 3, 6, and 9 months after baseline assessment. The Bergen Social Media Addiction Scale, Internet Gaming Disorder Scale-Short Form, and the Hospital Anxiety and Depression Scale were used to assess studied variables. Demographics including age, physical characteristics (i.e., height, weight, and body mass index), and cigarette use were compared between participants who completed all the follow-ups and those who dropped out. Random intercept cross-lagged models were constructed to understand the reciprocal relationships between PSMU, PG, and psychological distress. Results No significant differences were found in age, physical characteristics, and cigarette use between participants who completed all the follow-ups and those who dropped out. Findings indicated that a high level of PSMU significantly increased the level of anxiety and a high level of anxiety significantly increased the level of PSMU. A high level of PSMU significantly increased the level of depression but the level of depression did not significantly affect the level of PSMU. A high level of PG significantly increased the level of anxiety, but the level of anxiety did not significantly affect the level of PG. A high level of depression significantly increased the level of PG, but the level of depression did not significantly affect the level of PG. Conclusion The patterns of the causal relationship between PIU and psychological distress variables differ. A reciprocal relationship was only found between the level of PSMU and the level of anxiety. Moreover, the longitudinal design found no differences in the waves in terms of gaming by the participants.
Risk Assessment and Research Synthesis methodologies in food safety: two effective tools to provide scientific evidence into the Decision Making Process.

i ACKNOWLEDGEMENTS . iii TABLE OF CONTENTS . v LIST OF TABLES . ix LIST OF FIGURES . xi CHAPTER 1: FOOD SAFETY, TRADE, AND THE NEED FOR SCIENCE IN POLICY . 13