Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Validation of a 6-Gene Hypoxia-Related Prognostic Signature For Cholangiocarcinoma

Cholangiocarcinoma (CHOL) is highly malignant and has a poor prognosis. This study is committed to creating a new prognostic model based on hypoxia related genes. Here, we established a novel tumor hypoxia-related prognostic model consisting of 6 hypoxia-related genes by univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) algorithm to predict CHOL prognosis and then the risk score for each patient was calculated. The results showed that the patients with high-risk scores had poor prognosis compared with those with low-risk scores, which was verified as an independent predictor by multivariate analysis. The hypoxia-related prognostic model was validated in both TCGA and GEO cohorts and exhibited excellent performance in predicting overall survival in CHOL. The PPI results suggested that hypoxia-related genes involved in the model may play a central role in regulating the hypoxic state. In addition, the presence of IDH1 mutations in the high-risk group was high, and GSEA results showed that some metabolic pathways were upregulated, but immune response processes were generally downregulated. These factors may be potential reasons for the high-risk group with worse prognosis. The analysis of different immune regulation-related processes in the high- and low-risk groups revealed that the expression of genes related to immune checkpoints would show differences between these two groups. We further verified the expression of the oncogene PPFIA4 in the model, and found that compared with normal samples, CHOL patients were generally highly expressed, and the patients with high-expression of PPFIA4 had a poor prognosis. In summary, the present study may provide a valid prognostic model for bile duct cancer to inform better clinical management of patients.
Association between Usual Dietary Intake of Food Groups and DNA Methylation and Effect Modification by Metabotype in the KORA FF4 Cohort

Associations between diet and DNA methylation may vary among subjects with different metabolic states, which can be captured by clustering populations in metabolically homogenous subgroups, called metabotypes. Our aim was to examine the relationship between habitual consumption of various food groups and DNA methylation as well as to test for effect modification by metabotype. A cross-sectional analysis of participants (median age 58 years) of the population-based prospective KORA FF4 study, habitual dietary intake was modeled based on repeated 24-h diet recalls and a food frequency questionnaire. DNA methylation was measured using the Infinium MethylationEPIC BeadChip providing data on >850,000 sites in this epigenome-wide association study (EWAS). Three metabotype clusters were identified using four standard clinical parameters and BMI. Regression models were used to associate diet and DNA methylation, and to test for effect modification. Few significant signals were identified in the basic analysis while many significant signals were observed in models including food group-metabotype interaction terms. Most findings refer to interactions of food intake with metabotype 3, which is the metabotype with the most unfavorable metabolic profile. This research highlights the importance of the metabolic characteristics of subjects when identifying associations between diet and white blood cell DNA methylation in EWAS.
Microsatellite Characteristics of Silver Carp (Hypophthalmichthys molitrix) Genome and Genetic Diversity Analysis in Four Cultured Populations

Hypophthalmichthys molitrix is one of the four most important fish in China and has high breeding potential. However, simple sequence repeat (SSR) markers developed on H. molitrix genome level for genetic diversity analysis are limited. In this study, the distribution characteristics of SSRs in the assembled H. molitrix genome were analyzed, and new markers were developed to preliminarily evaluate the genetic diversity of the four breeding populations. A total of 368,572 SSRs were identified from the H. molitrix genome. The total length of SSRs was 6,492,076 bp, accounting for 0.77% of the total length of the genome sequence. The total frequency and total density were 437.73 loci/Mb and 7713.16 bp/Mb, respectively. Among the 2–6 different nucleotide repeat types, SSRs were dominated by di-nucleotide repeats (204,873, 55.59%), and AC/GT was the most abundant motif. The number of SSRs on each chromosome was positively correlated with the length. The 13 pairs of markers developed were used to analyze the genetic diversity of four cultivated populations in Hubei Province. The results showed that the genetic diversity of the four populations was low, and the ranges of alleles (Na), effective alleles (Ne), observed heterozygosity (Ho), and Shannon’s index information (I) were 3.538–4.462, 2.045–2.461, 0.392–0.450, and 0.879–0.954, respectively. Genetic variation occurs mainly among individuals within populations (95.35%). UPGMA tree and Bayesian analysis showed that four populations could be divided into two different branches. Therefore, the genome-wide SSRs were effectively in genetic diversity analysis on H. molitrix.
Auxiliary Pneumonia Classification Algorithm Based on Pruning Compression

Pneumonia infection is the leading cause of death in young children. The commonly used pneumonia detection method is that doctors diagnose through chest X-ray, and external factors easily interfere with the results. Assisting doctors in diagnosing pneumonia in patients based on deep learning methods can effectively eliminate similar problems. However, the complex network structure and redundant parameters of deep neural networks and the limited storage and computing resources of clinical medical hardware devices make it difficult for this method to use widely in clinical practice. Therefore, this paper studies a lightweight pneumonia classification network, CPGResNet50 (ResNet50 with custom channel pruning and ghost methods), based on ResNet50 pruning and compression to better meet the application requirements of clinical pneumonia auxiliary diagnosis with high precision and low memory. First, based on the hierarchical channel pruning method, the channel after the convolutional layer in the bottleneck part of the backbone network layer is used as the pruning object, and the pruning operation is performed after its normalization to obtain a network model with a high compression ratio. Second, the pruned convolutional layers are decomposed into original convolutions and cheap convolutions using the optimized convolution method. The feature maps generated by the two convolution parts are combined as the input to the next convolutional layer. Further, we conducted many experiments using pneumonia X-ray medical image data. The results show that the proposed method reduces the number of parameters of the ResNet50 network model from 23.7 M to 3.455 M when the pruning rate is 90%, a reduction is more than 85%, FIOPs dropped from 4.12G to 523.09 M, and the speed increased by more than 85%. The model training accuracy error remained within 1%. Therefore, the proposed method has a good performance in the auxiliary diagnosis of pneumonia and obtained good experimental results.
A novel aged mouse model of recurrent intracerebral hemorrhage in the bilateral striatum

The current animal models of stroke primarily model a single intracerebral hemorrhage (ICH) attack, and there is a lack of a reliable model of recurrent ICH. In this study, we established 16-month-old C57BL/6 male mouse models of ICH by injecting collagenase VII-S into the left striatum. Twenty-one days later, we injected collagenase VII-S into the right striatum to simulate recurrent ICH. Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage, delayed recovery in locomotor function, motor coordination, and movement speed, and more obvious emotional and cognitive dysfunction than mice subjected to unilateral striatal hemorrhage. These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH. These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.
ShVEEGc: EEG Clustering With Improved Cosine Similarity-Transformed Shapley Value

As the number of unlabeled or mislabeled electroencephalogram (EEG) increases dramatically in such applications as cerebral disease diagnosis, rehabilitation, and brain-computer interfaces, the supervised approaches that require labels or markers become inapplicable. Unfortunately, there are few reports on unsupervised studies for unlabeled EEG data, especially for unlabeled EEG clustering. To address the challenging task, we propose an effective approach named ShVEEGc for EEG clustering inspired by an improved Shapley value in cooperative game theory. The idea of ShVEEGc is first utilizing an improved cosine similarity to measure the correlations of EEG data and then calculating the improved Shapley value based on the inherent connection between unlabeled EEG data, which considers both global connections and local relationships potentially hidden in EEG data. Thus, ShVEEGc not only has good anti-interference ability but also can mine potential relationships among unlabeled EEG data. The comparison experiments with fourteen state-of-the-art EEG time series clustering algorithms on eleven real-world EEG datasets with four standard evaluation criteria demonstrate the efficacy and superiority of ShVEEGc for EEG clustering. Besides, the discussion on the impact of several different similarity measures on ShVEEGc also illustrates that the improved cosine similarity proposed in this paper is more suitable for EEG data.
Therapeutic Potential of Intrabodies for Cancer Immunotherapy: Current Status and Future Directions

Tumor cells are characterized by overexpressed tumor-associated antigens or mutated neoantigens, which are expressed on the cell surface or intracellularly. One strategy of cancer immunotherapy is to target cell-surface-expressed tumor-associated antigens (TAAs) with therapeutic antibodies. For targeting TAAs or neoantigens, adoptive T-cell therapies with activated autologous T cells from cancer patients transduced with novel recombinant TCRs or chimeric antigen receptors have been successfully applied. Many TAAs and most neoantigens are expressed in the cytoplasm or nucleus of tumor cells. As alternative to adoptive T-cell therapy, the mRNA of intracellular tumor antigens can be depleted by RNAi, the corresponding genes or proteins deleted by CRISPR-Cas or inactivated by kinase inhibitors or by intrabodies, respectively. Intrabodies are suitable to knockdown TAAs and neoantigens without off-target effects. RNA sequencing and proteome analysis of single tumor cells combined with computational methods is bringing forward the identification of new neoantigens for the selection of anti-cancer intrabodies, which can be easily performed using phage display antibody repertoires. For specifically delivering intrabodies into tumor cells, the usage of new capsid-modified adeno-associated viruses and lipid nanoparticles coupled with specific ligands to cell surface receptors can be used and might bring cancer intrabodies into the clinic.
Systematic Investigation of LC Miniaturization to Increase Sensitivity in Wide-Target LC-MS-Based Trace Bioanalysis of Small Molecules

Covering a wide spectrum of molecules is essential for global metabolome assessment. While metabolomics assays are most frequently carried out in microbore LC-MS analysis, reducing the size of the analytical platform has proven its ability to boost sensitivity for specific -omics applications. In this study, we elaborate the impact of LC miniaturization on exploratory small-molecule LC-MS analysis, focusing on chromatographic properties with critical impact on peak picking and statistical analysis. We have assessed a panel of small molecules comprising endogenous metabolites and environmental contaminants covering three flow regimes—analytical, micro-, and nano-flow. Miniaturization to the micro-flow regime yields moderately increased sensitivity as compared to the nano setup, where median sensitivity gains around 80-fold are observed in protein-precipitated blood plasma extract. This gain resulting in higher coverage at low µg/L concentrations is compound dependent. At the same time, the nano-LC-high-resolution mass spectrometry (HRMS) approach reduces the investigated chemical space as a consequence of the trap-and-elute nano-LC platform. Finally, while all three setups show excellent retention time stabilities, rapid gradients jeopardize the peak area repeatability of the nano-LC setup. Micro-LC offers the best compromise between improving signal intensity and metabolome coverage, despite the fact that only incremental gains can be achieved. Hence, we recommend using micro-LC for wide-target small-molecule trace bioanalysis and global metabolomics of abundant samples.
Housing cost burden and material hardship among older adults: How do they influence psychological health?

Despite a growing body of evidence for the association between housing cost burden and psychological health, few studies have focused on the potential mediators of this association and the extent to which housing cost burden poses a threat to older adults' psychological health. This study aims to assess (a) the link between housing cost burden and psychological health among older adults and (b) how the association is mediated by material hardship.
Detecting Hot Spots of Methane Flux Using Footprint‐Weighted Flux Maps

In this study, we propose a new technique for mapping the spatial heterogeneity in gas exchange around flux towers using flux footprint modeling and focusing on detecting hot spots of methane (CH4) flux. In the first part of the study, we used a CH4 release experiment to evaluate three common flux footprint models: the Hsieh model (Hsieh et al., 2000), the Kljun model (Kljun et al., 2015), and the K & M model (Kormann and Meixner, 2001), finding that the K & M model was the most accurate under these conditions. In the second part of the study, we introduce the Footprint‐Weighted Flux Map, a new technique to map spatial heterogeneity in fluxes. Using artificial CH4 release experiments, natural tracer approaches and flux chambers we mapped the spatial flux heterogeneity, and detected and validated a hot spot of CH4 flux in a oligohaline restored marsh. Through chamber measurements during the months of April and May, we found that fluxes at the hot spot were on average as high as 6589 ± 7889 nmol m−2 s−1 whereas background flux from the open water were on average 15.2 ± 7.5 nmol m−2 s−1. This study provides a novel tool to evaluate the spatial heterogeneity of fluxes around eddy‐covariance towers and creates important insights for the interpretation of hot spots of CH4 flux, paving the way for future studies aiming to understand subsurface biogeochemical processes and the microbiological conditions that lead to the occurrence of hot spots and hot moments of CH4 flux.
“I Feel Happy Again”: Methylphenidate Supports Health-Related Quality of Life in Survivors of Pediatric Brain Tumor

Background: The deleterious impact upon the cognitive development of survivors of pediatric brain tumors (PBT) is well documented. Impairment in cognitive function is associated with reduced health-related quality of life (HRQoL), such that survivors of PBT report difficulties in multiple distinct domains and an overall reduced quality of life. Studies of the use of methylphenidate in survivors of PBT to alleviate impairment in cognitive functions have shown some success. The current study aimed to explore the impact upon HRQoL in survivors of PBT of a trial of psychostimulant medication. Method: Data were collected from 12 pediatric neuro-oncology patients aged 7–17 years receiving methylphenidate treatment. HRQoL was measured using the PEDS QL quality of life self-report measure and a semi-structured questionnaire-based interview. Results: Analyses of data demonstrates benefit to five domains associated with HRQoL: social, emotional, academic, physical, and cognition. Conclusion: Survivors of PBT reported favorable views as to the subjective benefit of methylphenidate on post-treatment impairment of HRQoL. This medication may offer the potential for restoration of a sense of ‘normality’ of function following cancer treatment in this clinical population.
Primary Thrombophilia XVII: A Narrative Review of Sticky Platelet Syndrome in México

Sticky Platelet Syndrome (SPS) is a disorder characterized by platelet hyperaggregability, diagnosed by studying in vitro platelet aggregation with ADP and epinephrine. It is the second most common cause of thrombophilia in Mexican Mestizos and manifests as an autosomal dominant trait which, combined with other coagulopathies, contributes significantly to the morbidity and mortality of patients with primary thrombophilia. It is easily treatable with antiplatelet drugs; however, the methods for diagnosis are not readily available in all clinical laboratories and the disorder is often overlooked by most clinicians. Herein, we present the results of more than 20 years of Mexican experience with the study of SPS in a Mestizo population.
Dogs and the Good Life: A Cross-Sectional Study of the Association Between the Dog–Owner Relationship and Owner Mental Wellbeing

Dog ownership is believed to benefit owner wellbeing but, contrary to popular belief, there is limited evidence to suggest that simply owning a dog is associated with improved mental health. This mixed-methods study investigates whether dog owners with stronger relationships with their dogs experience better mental health. Participants (n = 1,693, adult United Kingdom dog owners) completed an online survey. Owners’ health was measured using the validated PROMIS questions regarding depression, anxiety, emotional support, and companionship. The dog–owner relationship was measured using the validated MDORS scale, which has three subscales: interaction, emotional closeness, and perceived costs. Univariable and multivariable linear regression analyses were conducted, adjusting for confounding factors. Additionally, positive and negative impacts of dog ownership on mental wellbeing were coded from open questions using thematic analysis. A stronger dog–owner relationship was associated with greater feelings of emotional support and companionship but poorer mental health in terms of anxiety or depression. However, the perceived costs (burden) subscale was consistently associated with better mental health outcomes. Direction of causality cannot be inferred as people with poor mental health may acquire dogs to help relieve symptoms, which qualitative analysis supported. Key themes included positive impacts on owner wellbeing and happiness through providing purpose, companionship and self-acceptance, pleasure and distraction, as well as lessening emotional pain and suffering and reducing risk behaviors. However, negative impacts of a strong relationship include anticipatory grief over loss of the dog, and concerns regarding the burden of responsibility and ability to meet dog’s needs. Perceived ability to adequately meet dog’s needs promoted personal growth and positive relationships with others, whereas perceived inability led to feelings of guilt, or anger/frustration, and reduced autonomy and sense of environmental mastery. Dog ownership contributes to both hedonic and eudaimonic wellbeing in multiple ways, including supporting owners through periods of poor mental health and providing purpose. However, the burden of responsibility and owner and dog characteristics can create challenges, and owners may benefit from support in caring for their dogs and reducing problematic behaviors.
Mental Health Support for Hospital Staff during the COVID-19 Pandemic: Characteristics of the Services and Feedback from the Providers

French authorities created mental health support services to accompany HCWs during the pandemic. We aimed to obtain feedback from staff providing these mental health support services within French hospitals to identify positive and negative features and avenues for improvement. A mixed-methods study was performed between 1 April and 30 June 2020. We contacted 77 centres to identify those providing mental health support services. We developed a questionnaire containing questions about the staff providing the service (quantitative part), with open questions to enable feedback from service providers (qualitative part). Of the 77 centres, 36 had mental health support services; 77.8% were created specifically for the epidemic. Services were staffed principally by psychologists, mainly used a telephone platform, and had a median opening time of 8 h/day. Thirty-seven professionals provided feedback, most aged 35–49 years. For 86.5%, it was their first time providing such support. Median self-reported comfort level was 8 (interquartiles 3–10), and 95% would do it again. Respondents reported (i) difficulties with work organisation, clinical situations, and lack of recognition and (ii) a desire for training. This study suggests that mental health support needs to be adapted to the needs of HCWs, both in terms of the content of the service and the timing of delivery.
Effects of skin‐to‐skin contact on full‐term infants’ stress reactivity and quality of mother–infant interactions

Abstract Skin‐to‐skin contact (SSC) between mothers and their infants has beneficial effects in both preterm and full‐term infants. Underlying mechanisms are largely unknown. This randomized controlled trial assessed whether daily SSC in full‐term mother–infant dyads: (1) decreases infants’ cortisol and behavioral reactivity to a mild naturalistic stressor, and (2) facilitates interaction quality between infants and mothers (i.e., improved maternal caregiving behavior and mother–infant adrenocortical synchrony). Pregnant Dutch women (N = 116) were recruited and randomly allocated to an SSC or care‐as‐usual condition. The SSC condition performed 1 h of SSC daily, from birth until postnatal week 5. In week 5, mothers bathed the infant (known mild stressor). Infant and maternal cortisol was sampled at baseline, 25 and 40 min after bathing, and infant and maternal behavior was rated. Results did not indicate effects of SSC on infant behavioral and cortisol reactivity to the bathing session. Similarly, no effect of SSC was found on maternal caregiving behavior and mother–infant adrenocortical synchrony. In conclusion, the findings provide no evidence that daily mother–infant SSC is associated with full‐term infants’ behavioral and adrenocortical stress reactivity or mother–infant interaction quality. Future studies should replicate these findings and unveil other potential mechanisms underlying beneficial effects of SSC.