Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and Validation of a Nine-Gene Amino Acid Metabolism-Related Risk Signature in HCC

Background: Hepatocellular carcinoma (HCC) is the world’s second most deadly cancer, and metabolic reprogramming is its distinguishing feature. Among metabolite profiling, variation in amino acid metabolism supports tumor proliferation and metastasis to the most extent, yet a systematic study on the role of amino acid metabolism-related genes in HCC is still lacking. An effective amino acid metabolism-related prediction signature is urgently needed to assess the prognosis of HCC patients for individualized treatment. Materials and Methods: RNA-seq data of HCC from the TCGA-LIHC and GSE14520 (GPL3921) datasets were defined as the training set and validation set, respectively. Amino acid metabolic genes were extracted from the Molecular Signature Database. Univariate Cox and LASSO regression analyses were performed to build a predictive risk signature. K-M curves, ROC curves, and univariate and multivariate Cox regression were conducted to evaluate the predictive value of this risk signature. Functional enrichment was analyzed by GSEA and CIBERSORTx software. Results: A nine-gene amino acid metabolism-related risk signature including B3GAT3, B4GALT2, CYB5R3, GNPDA1, GOT2, HEXB, HMGCS2, PLOD2, and SEPHS1 was constructed to predict the overall survival (OS) of HCC patients. Patients were separated into high-risk and low-risk groups based on risk scores and low-risk patients had lower risk scores and longer survival time. Univariate and multivariate Cox regression verified that this signature was an independent risk factor for HCC. ROC curves showed that this risk signature can effectively predict the 1-, 2-, 3- and 5-year survival times of patients with HCC. Additionally, prognostic nomograms were established based on the training set and validation set. These genes were closely correlated with the immune regulation. Conclusion: Our study identified a nine-gene amino acid metabolism-related risk signature and built predictive nomograms for OS in HCC. These findings will help us to personalize the treatment of liver cancer patients.
Short-Chain Inulin Modulates the Cecal Microbiota Structure of Leptin Knockout Mice in High-Fat Diet

The aim of this study was to explore the effect of short-chain inulin on cecal microbiota of high-fat diet-fed leptin knockout mice and the different influences of cecal microbiota on wild-type and leptin knockout mice. A total of 18 specific pathogen-free male C57BL/6J wild-type mice and 18 C57BL/6J leptin knockout mice (OB/OB mice) were selected. Mice were divided into six groups according to their genotype: wild-type mice have three groups, including the normal diet group (CT), 60% high-fat diet group (CH), and 60% high fat with 10% short-chain inulin group (CHI); OB/OB mice were also divided into three groups, including the normal diet group (OT), 60% high-fat diet group (OH), and 60% high fat with 10% short-inulin group (OHI). The mice were fed for 8 weeks to analyze the diversity of cecal microbiota. The results show that compared with CH and OH, the variety of cecal microbiota was significantly reduced in CH and OH and further reduced in CHI and OHI. Bifidobacterium and Lactobacillus are the biomarkers in genus level. Dietary short-chain inulin significantly enhanced Bifidobacterium in OHI compared with OH (p < 0.01) and significantly reduced in CHI and compared with CH (p < 0.01). Lactobacillus was significantly enhanced in CHI and OHI compared with CH and OH, respectively (p < 0.01). Blautia was significantly enhanced in CH and OH compared with other groups (p < 0.01). Both Escherichia-Shigella and Enterococcus were significantly reduced in CHI and OHI, compared with CH and OH, respectively (p < 0.05). Escherichia-Shigella was even lower than CT and OT in CHI and OHI. Functional prediction of microbial communities showed that the abundance of amino acid sugar and nucleotide sugar metabolism pathways were significantly enhanced (p < 0.05) in CH and OH, and OH was significantly higher than CH (p < 0.05). Among the leptin knockout groups, PICRUSt2 function prediction showed that the fatty acid metabolism pathway significantly reduced (p < 0.05) in OHI and OT compared with OH. In conclusion, short-chain inulin modulated the dysbiosis induced by high-fat diet, improved probiotics growth and inhibited conditioned pathogenic bacteria, and the influences were significantly different in wild-type and leptin knockout mice.
Central Systolic Blood Pressure Is Associated With Early Vascular Damage in Children and Adolescents With Type 1 Diabetes

Objective of the study: This study aimed to test the effect of multiple cardiovascular risk factors on subclinical indices of atherosclerosis in children and adolescents with type 1 diabetes (T1D). Methods: Carotid intima-media thickness (cIMT), carotid distensibility coefficient (cDC), and carotid–femoral pulse wave velocity (PWV) were measured in children and adolescents with T1D, in a follow-up at the outpatient clinics of Verona. Blood pressure (BP; both central and peripheral), metabolic and other cardiovascular risk factors were evaluated in multivariate linear regressions to assess the association with the measured indices of subclinical vascular damage. Results: One hundred and twenty-six children and adolescents were included. cIMT was above the 95th percentile for age and height in 60.8% of the population, whereas 26% of the sample had cDC impairment (less than the 5th percentile) and 4.8% had an elevated PWV. Independent determinants of cIMT according to the regression models were only gender type of glucose monitoring and central systolic BP (cSBP). PWV was associated with age, sex, heart rate, and cSBP; cDC with age and both cSBP and, alternatively, peripheral BP (pBP). Neither pBP nor any of the tested metabolic parameters, including glycated hemoglobin, was associated with PWV and cIMT. Conclusions: A high proportion of early vascular damage, especially an increased cIMT, is present in children and adolescents with T1D in whom cSBP seems to be a common determinant. In children and adolescents with T1DM, a special focus should be on hemodynamic risk factors beyond metabolic ones.
Exploring Klebsiella pneumoniae in Healthy Poultry Reveals High Genetic Diversity, Good Biofilm-Forming Abilities and Higher Prevalence in Turkeys Than Broilers

Klebsiella pneumoniae is a well-studied human pathogen for which antimicrobial resistant and hypervirulent clones have emerged globally. K. pneumoniae is also present in a variety of environmental niches, but currently there is a lack of knowledge on the occurrence and characteristics of K. pneumoniae from non-human sources. Certain environmental niches, e.g., animals, may be associated with high K. pneumoniae abundance, and these can constitute a reservoir for further transmission of strains and genetic elements. The aim of this study was to explore and characterize K. pneumoniae from healthy broilers and turkeys. A total of 511 cecal samples (broiler n = 356, turkey n = 155), included in the Norwegian monitoring program for antimicrobial resistance (AMR) in the veterinary sector (NORM-VET) in 2018, were screened for K. pneumoniae by culturing on SCAI agar. K. pneumoniae was detected in 207 (40.5%) samples. Among the broiler samples, 25.8% were positive for K. pneumoniae, in contrast to turkey with 74.2% positive samples (p < 0.01). Antibiotic susceptibility testing was performed, in addition to investigating biofilm production. Whole genome sequencing was performed on 203 K. pneumoniae isolates, and analysis was performed utilizing comparative genomics tools. The genomes grouped into 66 sequence types (STs), with ST35, ST4710 and ST37 being the most prevalent at 13.8%, 7.4%, and 5.4%, respectively. The overall AMR occurrence was low, with only 11.3% of the isolates showing both pheno- and genotypic resistance. Genes encoding aerobactin, salmochelin or yersiniabactin were detected in 47 (23.2%) genomes. Fifteen hypervirulent genomes belonging to ST4710 and isolated from turkey were identified. These all encoded the siderophore virulence loci iuc5 and iro5 on an IncF plasmid. Isolates from both poultry species displayed good biofilm-forming abilities with an average of OD595 0.69 and 0.64. To conclude, the occurrence of K. pneumoniae in turkey was significantly higher than in broiler, indicating that turkey might be an important zoonotic reservoir for K. pneumoniae compared to broilers. Furthermore, our results show a highly diverse K. pneumoniae population in poultry, low levels of antimicrobial resistance, good biofilm-forming abilities and a novel hypervirulent ST4710 clone circulating in the turkey population.
Digital Shared Decision-Making Interventions in Mental Healthcare: A Systematic Review and Meta-Analysis

Background: Shared decision-making (SDM) in mental healthcare has received increased attention as a process to reinforce person-centered care. With the rapid development of digital health technology, researchers investigate how digital interventions may be utilized to support SDM. Despite the promise of digital interventions to support SDM, the effect of these in mental healthcare has not been evaluated before. Thus, this paper aims to assess the effect of SDM interventions complimented by digital technology in mental healthcare. Objective: The objective of this review was to systematically examine the effectiveness of digital SDM interventions on patient outcomes as investigated in randomized trials. Methods: We performed a systematic review and meta-analysis of randomized controlled trials on digital SDM interventions for people with a mental health condition. We searched for relevant studies in MEDLINE, PsycINFO, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials. The search strategy included terms relating to SDM, digital systems, mental health conditions, and study type. The primary outcome was patient activation or indices of the same (e.g., empowerment and self-efficacy), adherence to treatment, hospital admissions, severity of symptoms, and level of functioning. Secondary outcomes were satisfaction, decisional conflict, working alliance, usage, and adherence of medicine; and adverse events were defined as harms or side effects. Results: Sixteen studies met the inclusion criteria with outcome data from 2,400 participants. Digital SDM interventions had a moderate positive effect as compared with a control condition on patient activation [standardized mean difference (SMD) = 0.56, CI: 0.10, 1.01, p = 0.02], a small effect on general symptoms (SMD = −0.17, CI: −0.31, −0.03, p = 0.02), and working alliance (SMD = 0.21, CI: 0.02, 0.41, p = 0.03) and for improving decisional conflict (SMD = −0.37, CI: −0.70, −0.05, p = 0.02). No effect was found on self-efficacy, other types of mental health symptoms, adverse events, or patient satisfaction. A total of 39 outcomes were narratively synthesized with results either favoring the intervention group or showing no significant differences between groups. Studies were generally assessed to have unclear or high risk of bias, and outcomes had a Grading of Recommendations Assessment, Development and Evaluation (GRADE) rating of low- or very low-quality evidence. Conclusions: Digital interventions to support SDM may be a promising tool in mental healthcare; but with the limited quality of research, we have little confidence in the estimates of effect. More quality research is needed to further assess the effectiveness of digital means to support SDM but also to determine which digital intervention features are most effective to support SDM. Systematic Review Registration: PROSPERO, identifier CRD42020148132.
A Real-Time Wearable System for Monitoring Vital Signs of COVID-19 Patients in a Hospital Setting

The challenges presented by the Coronavirus disease 2019 (COVID-19) pandemic to the National Health Service (NHS) in the United Kingdom (UK) led to a rapid adaptation of infection disease protocols in-hospital. In this paper we report on the optimisation of our wearable ambulatory monitoring system (AMS) to monitor COVID-19 patients on isolation wards. A wearable chest patch (VitalPatch®, VitalConnect, United States of America, USA) and finger-worn pulse oximeter (WristOx2® 3150, Nonin, USA) were used to estimate and transmit continuous Heart Rate (HR), Respiratory Rate (RR), and peripheral blood Oxygen Saturation (SpO2) data from ambulatory patients on these isolation wards to nurse bays remote from these patients, with a view to minimising the risk of infection for nursing staff. Our virtual High-Dependency Unit (vHDU) system used a secure web-based architecture and protocols (HTTPS and encrypted WebSockets) to transmit the vital-sign data in real time from wireless Android tablet devices, operating as patient data collection devices by the bedside in the isolation rooms, into the clinician dashboard interface available remotely via any modern web-browser. Fault-tolerant software strategies were used to reconnect the wearables automatically, avoiding the need for nurses to enter the isolation ward to re-set the patient monitoring equipment. The remote dashboard also displayed the vital-sign observations recorded by the nurses, using a separate electronic observation system, allowing them to review both sources of vital-sign data in one integrated chart. System usage was found to follow the trend of the number of local COVID-19 infections during the first wave of the pandemic in the UK (March to June 2020), with almost half of the patients on the isolation ward monitored with wearables during the peak of hospital admissions in the local area. Patients were monitored for a median of 31.5 [8.8, 75.4] hours, representing 88.1 [62.5, 94.5]% of the median time they were registered in the system. This indicates the system was being used in the isolation ward during this period. An updated version of the system has now also been used throughout the second and third waves of the pandemic in the UK.
Short and Long-Term Effects of Growth Hormone in Children and Adolescents With GH Deficiency

The syndrome of impaired GH secretion (GH deficiency) in childhood and adolescence had been identified at the end of the 19th century. Its non-acquired variant (naGHD) is, at childhood onset, a rare syndrome of multiple etiologies, predominantly characterized by severe and permanent growth failure culminating in short stature. It is still difficult to diagnose GHD and, in particular, to ascertain impaired GH secretion in comparison to levels in normally-growing children. The debate on what constitutes an optimal diagnostic process continues. Treatment of the GH deficit via replacement with cadaveric pituitary human GH (pit-hGH) had first been demonstrated in 1958, and opened an era of therapeutic possibilities, albeit for a limited number of patients. In 1985, the era of recombinant hGH (r-hGH) began: unlimited supply meant that substantial long-term experience could be gained, with greater focus on efficacy, safety and costs. However, even today, the results of current treatment regimes indicate that there is still a substantial fraction of children who do not achieve adult height within the normal range. Renewed evaluation of height outcomes in childhood-onset naGHD is required for a better understanding of the underlying causes, whereby the role of various factors - diagnostics, treatment modalities, mode of treatment evaluation - during the important phases of child growth - infancy, childhood and puberty - are further explored.
Operational Determination of Subjective Cognitive Decline, Mild Cognitive Impairment, and Dementia Using Sum of Boxes of the Clinical Dementia Rating Scale

Objectives: The Clinical Dementia Rating (CDR) Scale is the gold standard for the staging of dementia due to Alzheimer's disease (AD). However, the application of CDR for the staging of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in AD remains controversial. This study aimed to use the sum of boxes of the CDR (CDR-SB) plus an SCD single questionnaire to operationally determine the different stages of cognitive impairment (CI) due to AD and non-AD. Methods: This was a two-phase study, and we retrospectively analyzed the Show Chwan Dementia registry database using the data selected from 2015 to 2020. Individuals with normal cognition (NC), SCD, MCI, and mild dementia (MD) due to AD or non-AD with a CDR < 2 were included in the analysis. Results: A total of 6,946 individuals were studied, including 875, 1,009, 1,585, and 3,447 with NC, SCD, MCI, and MD, respectively. The cutoff scores of CDR-SB for NC/SCD, SCD/MCI, and MCI/dementia were 0/0.5, 0.5/1.0, and 2.5/3.0, respectively. The receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) values of the test groups were 0.85, 0.90, and 0.92 for discriminating NC from SCD, SCD from MCI, and MCI from dementia, respectively. Compared with the Cognitive Abilities Screening Instrument or the Montreal Cognitive Assessment, the use of CDR-SB is less influenced by age and education. Conclusion: Our study showed that the operational determination of SCD, MCI, and dementia using the CDR-SB is practical and can be applied in clinical settings and research on CI or dementia.
Temperature and Patterns of Occurrence and Abundance of Key Copepod Taxa in the Northeast Pacific

The Northeast Pacific is a highly heterogeneous and productive ecosystem, yet it is vulnerable to climate change and extreme events such as marine heat waves. Recent heat wave induced die-offs of fish, marine mammals, and seabirds in the Gulf of Alaska were associated with the loss of large, lipid-rich copepods, which are a vital food resource for forage fishes. The critical and temperature sensitive role of copepods in this ecosystem motivates our investigation into the impacts of temperature on copepod occurrence, abundance, and phenology. Here, we pair long term in situ copepod data from Continuous Plankton Recorder surveys with satellite temperature data to determine the influence of water temperature on three key copepod taxa: Neocalanus plumchrus, Calanus pacificus, and Oithona spp. Through the use of linear models and thermal threshold methods, we demonstrate that N. plumchrus is most vulnerable to warming and future marine heat waves in this region. Linear models demonstrate that N. plumchrus abundance is negatively related to temperature, and thermal threshold methods reveal that N. plumchrus has an upper thermal threshold of 11.5°C for occurrence, and 10.5°C for abundance. Additionally, examining N. plumchrus abundance before and during the 2014–2016 marine heat wave demonstrates reduced species abundance during past warming events. Oithona spp. and C. pacificus appear to be less vulnerable to warm temperatures. However, their presence will not be sufficient to supplement the loss of the larger-bodied and lipid-rich N. plumchrus. Our findings demonstrate the power of using long-term in situ data to determine thermal tolerances, and suggest the need to further examine the potential resilience of N. plumchrus to climate change.
In a Manner of Speaking: How Reported Speech May Have Shaped Grammar

We present a first, broad-scale typology of extended reported speech, examples of lexicalised or grammaticalised reported speech constructions without a regular quotation meaning. These typically include meanings that are conceptually close to reported speech, such as think or want, but also interpretations that do not appear to have an obvious conceptual relation with talking, such as cause or begin to. Reported speech may therefore reflect both concepts of communication and inner worlds, and meanings reminiscent of ‘core grammar’, such as evidentiality, modality, aspect (relational) tense and clause linking. We contextualise our findings in the literature on fictive interaction and perspective and suggest that extended reported speech may lend insight into a fundamental aspect of grammar: the evolution of verbal categories. Based on the striking similarity between the meanings of extended reported speech and grammatical categories, we hypothesise that the phenomenon represents a plausible linguistic context in which grammar evolved.
Plasma Metabolome Profiling for the Diagnosis of Catecholamine Producing Tumors

Context Pheochromocytomas and paragangliomas (PPGL) cause catecholamine excess leading to a characteristic clinical phenotype. Intra-individual changes at metabolome level have been described after surgical PPGL removal. The value of metabolomics for the diagnosis of PPGL has not been studied yet. Objective Evaluation of quantitative metabolomics as a diagnostic tool for PPGL. Design Targeted metabolomics by liquid chromatography-tandem mass spectrometry of plasma specimens and statistical modeling using ML-based feature selection approaches in a clinically well characterized cohort study. Patients Prospectively enrolled patients (n=36, 17 female) from the Prospective Monoamine-producing Tumor Study (PMT) with hormonally active PPGL and 36 matched controls in whom PPGL was rigorously excluded. Results Among 188 measured metabolites, only without considering false discovery rate, 4 exhibited statistically significant differences between patients with PPGL and controls (histidine p=0.004, threonine p=0.008, lyso PC a C28:0 p=0.044, sum of hexoses p=0.018). Weak, but significant correlations for histidine, threonine and lyso PC a C28:0 with total urine catecholamine levels were identified. Only the sum of hexoses (reflecting glucose) showed significant correlations with plasma metanephrines. By using ML-based feature selection approaches, we identified diagnostic signatures which all exhibited low accuracy and sensitivity. The best predictive value (sensitivity 87.5%, accuracy 67.3%) was obtained by using Gradient Boosting Machine Modelling. Conclusions The diabetogenic effect of catecholamine excess dominates the plasma metabolome in PPGL patients. While curative surgery for PPGL led to normalization of catecholamine-induced alterations of metabolomics in individual patients, plasma metabolomics are not useful for diagnostic purposes, most likely due to inter-individual variability.