Miracle-dz/UniFAR-FTUs huggingface dataset:
Ability of Noninvasive Scoring Systems to Identify Individuals in the Population at Risk for Severe Liver Disease.

BACKGROUND & AIMS Non-invasive scoring systems are used to identify persons with advanced liver fibrosis. We investigated the ability of scoring systems to identify individuals in the general population at risk for future liver-related events. METHODS We collected data from the Swedish Apolipoprotein Mortality Risk cohort on persons 35-79 years old who had blood samples collected from 1985 through 1996. We collected APRI (n=127,302), BARD (n=75,303), FIB-4 (n=126,941), Forns (n=122,419), and the nonalcoholic fatty liver disease (NAFLD) fibrosis scores (NFS, n=13,160). We ascertained incident cases of cirrhosis or complications by linking Swedish health data registers. Cox regression was used to estimate hazard ratios (HRs) for severe liver disease at 5, 10, and a maximum follow-up time of 27 years. The predictive ability of the scores was evaluated using area under the receiver operating characteristic (AUROC) curve and C-statistics analyses. Our specific aims were to investigate the predictive capabilities of scoring systems for fatal and non-fatal liver disease, determine which scoring system has the highest level of accuracy, and investigate the predictive abilities of the scoring systems in persons with a higher probability of NAFLD at baseline. RESULTS A similar proportion of individuals evaluated by each scoring system developed cirrhosis or complications thereof (1.0%-1.4%). The incidence of any outcome was increased in intermediate- and high-risk groups compared with low-risk groups, with HRs at 10 years in the high-risk group ranging from 1.67 for the BARD score to 45.9 for the APRI score. The predictive abilities of all scoring systems decreased with time and were higher in men. All scoring systems were more accurate in persons with risk factors for NAFLD at baseline, with AUROCs reaching 0.83. CONCLUSIONS Higher scores from non-invasive scoring systems to evaluate fibrosis are associated with an increased risk of cirrhosis in a general population, but their predictive ability is modest. Performance was better when patients were followed for shorter time periods and in persons with a higher risk of NAFLD, with AUROC values reaching 0.83. New scoring systems are needed to evaluate risk of fibrosis in the general population and in primary care.
Latent cellular analysis robustly reveals subtle diversity in large-scale single-cell RNA-seq data

Abstract Single-cell RNA sequencing (scRNA-seq) is a powerful tool for characterizing the cell-to-cell variation and cellular dynamics in populations which appear homogeneous otherwise in basic and translational biological research. However, significant challenges arise in the analysis of scRNA-seq data, including the low signal-to-noise ratio with high data sparsity, potential batch effects, scalability problems when hundreds of thousands of cells are to be analyzed among others. The inherent complexities of scRNA-seq data and dynamic nature of cellular processes lead to suboptimal performance of many currently available algorithms, even for basic tasks such as identifying biologically meaningful heterogeneous subpopulations. In this study, we developed the Latent Cellular Analysis (LCA), a machine learning–based analytical pipeline that combines cosine-similarity measurement by latent cellular states with a graph-based clustering algorithm. LCA provides heuristic solutions for population number inference, dimension reduction, feature selection, and control of technical variations without explicit gene filtering. We show that LCA is robust, accurate, and powerful by comparison with multiple state-of-the-art computational methods when applied to large-scale real and simulated scRNA-seq data. Importantly, the ability of LCA to learn from representative subsets of the data provides scalability, thereby addressing a significant challenge posed by growing sample sizes in scRNA-seq data analysis.
Vestibular Evoked Myogenic Potentials in Patients With Low Vitamin B12 Levels

Objective: Vitamin B12 deficiency-induced hyperhomocysteinemia has been associated with impaired microarterial flow, demyelization, and neuronal damage, resulting in cochlear damage and auditory dysfunction. Therefore, we aimed to evaluate the possible vestibular-evoked myogenic potential (VEMP) abnormalities in patients with vitamin B12 deficiency. Material and Method: In this prospective study, 37 patients diagnosed with vitamin B12 deficiency (<220 pg/mL) were compared with 31 audiologically healthy participants with normal B12 levels. Burst-evoked cervical VEMP (cVEMP) measurements were performed on all participants. Additionally, cVEMP responses were analyzed for P1-N1 latency, interpeak amplitude, and amplitude asymmetry ratio. The results of audiometric examination and VEMP records as well as absent responses were evaluated and compared between groups. Results: The rate of absent VEMP responses was twice as high in the patient group than in the healthy control group (12 vs 6 cases, respectively). Moreover, the mean values of interpeak amplitude in both right and left ears were statistically shorter in the patient group than the control group (P values = .024 and .007, respectively). Similarly, the mean amplitude asymmetry ratio was statistically higher in the patient group than the control group (P = .050). There were no statistically significant differences in latency responses between groups. Furthermore, positive, statistically significant correlation was detected between values of the left P1-N1 interpeak amplitude and vitamin B12 levels (r = 0.287, P = .037). Conclusions: Increased rates of absent VEMPs and decreased amplitudes with normal latencies are attributed to peripheral vestibular hypofunction in patients with vitamin B12 deficiency.
The difference of detection rate of avian influenza virus in the wild bird surveillance using various methods

Korea is located within the East Asian-Australian flyway of wild migratory birds during the fall and winter seasons. Consequently, the likelihood of introduction of numerous subtypes and pathotypes of the Avian influenza (AI) virus to Korea has been thought to be very high. In the current study, we surveyed wild bird feces for the presence of AI virus that had been introduced to Korea between September 2017 and February 2018. To identify and characterize the AI virus, we employed commonly used methods, namely, virus isolation (VI) via egg inoculation, real-time reverse transcription-polymerase chain reaction (rRT-PCR), conventional RT-PCR (cRT-PCR) and a newly developed next generation sequencing (NGS) approach. In this study, 124 out of 11,145 fresh samples of wild migratory birds tested were rRT-PCR positive; only 52.0% of VI positive samples were determined as positive by rRT-PCR from fecal supernatant. Fifty AI virus specimens were isolated from fresh fecal samples and typed. The cRT-PCR subtyping results mostly coincided with the NGS results, although NGS detected the presence of 11 HA genes and four NA genes that were not detected by cRT-PCR. NGS analysis confirmed that 12% of the identified viruses were mixed-subtypes which were not detected by cRT-PCR. Prevention of the occurrence of AI virus requires a workflow for rapid and accurate virus detection and verification. However, conventional methods of detection have some limitations. Therefore, different methods should be combined for optimal surveillance, and further studies are needed in aspect of the introduction and application of new methods such as NGS.
An overview of the adverse effects of cannabis use for Canadian physicians.

PURPOSE Cannabis is the most widely used illicit substance and one of the most commonly used psychoactive substances in the world, preceded only by alcohol, tobacco and caffeine. Recent changes in legislation regarding cannabis use in Canada and potential upcoming changes worldwide may have a further impact on the prevalence of cannabis use. Thus, it is critical to understand the risks and potential adverse health effects of acute and long-term cannabis use. Current literature is lacking in many areas surrounding cannabis use, and for the most part is unable to provide clear associations once confounding variables are considered. Here we provide a general overview of the history of cannabis, the physical and mental health consequences, and the risks to specific groups. SOURCE A scoping search of published articles in PubMed from the start date (1946) until 2018. PRINCIPAL FINDING Current evidence supports an association between cannabis use and mild respiratory and cardiac effects, but no clear increased risk of cancer. Psychiatric disorders, including schizophrenia and anxiety, show associations with cannabis use; however, a causal effect of cannabis use is unclear. While no evidence for increased risk in pregnancy has been found, risk is still undetermined. Youth may be at a greater risk as earlier initiation of use increases the risk of adverse health effects. CONCLUSION Overall, evidence for direct and long-term adverse effects of cannabis use is minimal and additional longitudinal studies will be required to better delineate unidentified effects.
Outcomes of total hip arthroplasty in haemodialysis and renal transplant patients: systematic review

Background: Chronic renal failure is increasing in prevalence and reported to have deleterious effects on the outcome of total hip arthroplasty (THA). Aim: To investigate the clinical and functional outcomes of THA in patients receiving haemodialysis or who have previously undergone renal transplantation. Methods: Systematic review of the literature using bibliographic databases up to July 2018 to determine the functional outcome, complications and revision rates of THA in patients receiving haemodialysis for end-stage renal failure and those with a previous renal transplant. Results: 25 studies were identified with a total of 797 THAs. 166 patients (20.8%) were receiving haemodialysis and 631 patients (79.2%) had undergone transplantation. All studies reported a marked improvement in hip function following THA. There were 27 failures (15.7% revision rate) in the haemodialysis group and 101 failures (16.0% revision rate) in the transplant group. The revision rate for cemented implants was higher in haemodialysis versus transplant patients (23% vs. 15%), with the converse being true for uncemented implants (3.8% vs. 6.9%). The deep infection rate was higher in the haemodialysis group (10.8% vs. 2.1%). Conclusions: Patients receiving haemodialysis or with a history of renal transplantation can expect good functional outcome following THA. However, the revision rate and deep infection rate are higher than would be expected in patients receiving THA for primary OA. Aseptic loosening is the most common reason for revision. Uncemented implants appear to be associated with lower failure rates both in haemodialysis patients and those who have had a transplant.
A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial

Objectives To compare efficacy and safety of ixekizumab (IXE) to adalimumab (ADA) in biological disease-modifying antirheumatic drug-naïve patients with both active psoriatic arthritis (PsA) and skin disease and inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARDs). Methods Patients with active PsA were randomised (1:1) to approved dosing of IXE or ADA in an open-label, head-to-head, blinded assessor clinical trial. The primary objective was to evaluate whether IXE was superior to ADA at week 24 for simultaneous achievement of a ≥50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100). Major secondary objectives, also at week 24, were to evaluate whether IXE was: (1) non-inferior to ADA for achievement of ACR50 and (2) superior to ADA for PASI100 response. Additional PsA, skin, treat-to-target and quality-of-life outcome measures were assessed at week 24. Results The primary efficacy endpoint was met (IXE: 36%, ADA: 28%; p=0.036). IXE was non-inferior for ACR50 response (IXE: 51%, ADA: 47%; treatment difference: 3.9%) and superior for PASI100 response (IXE: 60%, ADA: 47%; p=0.001). IXE had greater response versus ADA in additional PsA, skin, nail, treat-to-target and quality-of-life outcomes. Serious adverse events were reported in 8.5% (ADA) and 3.5% (IXE) of patients. Conclusions IXE was superior to ADA in achievement of simultaneous improvement of joint and skin disease (ACR50 and PASI100) in patients with PsA and inadequate response to csDMARDs. Safety and tolerability for both biologicals were aligned with established safety profiles.
Emerging Contribution of Histopathology to Our Understanding of Chronic Rhinosinusitis Endotypes: Tissue Eosinophil Count and Aggregates

Background Rhinologists are currently trying to find evidence useful for classifying chronic rhinosinusitis with nasal polyps (CRSwNP) in terms of pathophysiology-based endotypes. This would help us to tailor targeted therapies and follow-up protocols to each patient, improving treatment efficacy and reducing relapse risk. The histopathological study of inflammatory cells in tissue and their tendency to form aggregates has shown promise in determining the pathogenesis and predicting the clinical outcome. Objective The main purpose of this study was to assess tissue eosinophil count, eosinophil aggregation, and their relationship to different CRSwNP phenotypes. Methods A consecutive series of 96 patients who underwent endoscopic sinus surgery for CRSwNP was retrospectively assessed. Our structured histopathological approach considered eosinophil count and eosinophil aggregates. Results Patients’ clinical features included allergic fungal rhinosinusitis (AFRS) in 17 cases, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD) in 19 cases, intrinsic asthma in 18 cases, extrinsic asthma in 21 cases, and allergy in 21 cases. Statistical analysis revealed more eosinophil aggregates in patients with NERD than in those with AFRS (P = .020), intrinsic asthma (P = .019), or extrinsic asthma (P = .029). NERD patients had a significantly higher tissue eosinophil count than the other groups considered, apart from the AFRS ones. AFRS patients had a higher tissue eosinophil count than patients with intrinsic asthma. Conclusion Our results showed in particular that the NERD patient group’s rhinosinusitis was sustained by a significantly more severe eosinophilic reaction than in the other groups. Structured histopathology can provide useful information for classifying CRSwNP on pathophysiological grounds.
Synthesis and biological evaluation of a MraY selective analogue of tunicamycins

Abstract Tunicamycins, which are nucleoside natural products, inhibit both bacterial phospho-N-acetylmuraminic acid (MurNAc)-pentapeptide translocase (MraY) and human UDP-N-acetylglucosamine (GlcNAc): polyprenol phosphate translocase (GPT). The improved synthesis and detailed biological evaluation of an MraY-selective inhibitor, 2, where the GlcNAc moiety was modified to a MurNAc amide, has been described.
Male Vocal Quality and Its Relation to Females’ Preferences

In both correlational and experimental settings, studies on women’s vocal preferences have reported negative relationships between perceived attractiveness and men’s vocal pitch, emphasizing the idea of an adaptive preference. However, such consensus on vocal attractiveness has been mostly conducted with native English speakers, but a few evidence suggest that it may be culture-dependent. Moreover, other overlooked acoustic components of vocal quality, such as intonation, perceived breathiness and roughness, may influence vocal attractiveness. In this context, the present study aims to contribute to the literature by investigating vocal attractiveness in an underrepresented language (i.e., French) as well as shedding light on its relationship with understudied acoustic components of vocal quality. More specifically, we investigated the relationships between attractiveness ratings as assessed by female raters and male voice pitch, its variation, the formants’ dispersion and position, and the harmonics-to-noise and jitter ratios. Results show that women were significantly more attracted to lower vocal pitch and higher intonation patterns. However, they did not show any directional preferences for all the other acoustic features. We discuss our results in light of the adaptive functions of vocal preferences in a mate choice context.
The TCL1 function revisited focusing on metabolic requirements of stemness

ABSTRACT The oncogenic ability of the T-cell leukemia/lymphoma 1 gene, TCL1, has captured the attention in the field of prolymphocytic T-cell and B-cell chronic leukemias for more than two decades. However, the finding that TCL1 is also expressed in totipotent cells of the mouse preimplantation embryos and that it is among the 10 genes, including the transcription factors Nanog, Oct4, Sox2, Tbx3, and Esrrb, that are required for maintaining the mitotic self-renewal state of embryonic stem cells, raises a great interest. In this review, we highlight newly acquired evidence pinpointing TCL1 as a crucial regulator of metabolic pathways that dictate somatic cell reprogramming toward pluripotency. In our opinion, this feature provides a relevant hint for reframing the role that this factor plays at early stages of mammalian embryo development and in tumorigenesis. Hence, the TCL1-dependent enhancement of serine/threonine AKT/PKB kinase activity favoring cell proliferation appears to be associated to the promotion of glucose transport and activation of glycolytic pathways. This is also consistent with the TCL1 ability to suppress mitochondrial biogenesis and oxygen consumption, downplaying the contribution of oxidative phosphorylation to energy metabolism. It thus appears that TCL1 masters the direction of energy metabolism toward the glycolytic pathway to meet a critical metabolic requirement that goes beyond the mere ATP production. For instance, the synthesis of glycolytic intermediates that are required for DNA synthesis likely represents the most pressing cellular need for both cleavage-stage embryos and rapidly proliferating tumor cells.
Macrophage polarization in chronic kidney disease: a balancing act between renal recovery or decline?

Macrophages are heterogenous cells of the innate immune system that can fluidly modulate their phenotype to respond to their local microenvironment. They are found throughout the renal compartments where they contribute to homeostasis and function. However, renal injury activates molecular pathways that initially stimulate differentiation of macrophages into a pro-inflammatory M1 phenotype. Later in the course of healing, abundant apoptotic debris and anti-inflammatory cytokines induce production of anti-inflammatory M2 macrophages which contribute to tissue regeneration and repair. Thus, the dynamic balance of M1 and M2 populations may outline the burden of inflammation and the process of tissue repair that define renal outcomes, which has been the impetus for therapeutic efforts targeting macrophages. This mini-review will discuss the role of these phenotypes in the progression of chronic renal injury, potential pathogenic mechanisms, and the promise of macrophage-based therapeutic applications for chronic kidney disease.
The Perception of Cantonese Vowel Length Contrast by Mandarin Speakers

The study investigates the perception of vowel length contrasts in Cantonese by native Mandarin speakers with varying degrees of experience in Cantonese: naïve listeners (no exposure), inexperienced learners (~1 year), and experienced learners (~5 years). While vowel length contrasts do not exist in Mandarin, they are, to some extent, exploited in English, the second language (L2) of all the participants. Using an AXB discrimination task, we investigate how native and L2 phonological knowledge affects the acquisition of vowel length contrasts in a third language (L3). The results revealed that all participant groups could discriminate three contrastive vowel pairs (/aː/–/ɐ/, /ɛː/–/e/, /ɔː/–/o/), but their performance was influenced by the degree of Cantonese exposure, particularly for learners in the early stage of acquisition. In addition to vowel quality differences, durational differences were proposed to explain the perceptual patterns. Furthermore, L2 English perception of the participants was found to modulate the perception of L3 Cantonese vowel length contrasts. Our findings demonstrate the bi-directional interaction between languages acquired at different stages, and provide concrete data to evaluate some speech acquisition models.
β2 Adrenergic receptor-mediated signaling regulates the immunosuppressive potential of myeloid-derived suppressor cells.

Catecholamines released by sympathetic nerves can activate adrenergic receptors present on nearly every cell type, including myeloid derived suppressor cells (MDSCs). Using in vitro systems and murine tumor models, in wild-type mice and genetically modified (β2-AR-/-) mice, as well adoptive transfer approaches, we found that the degree of β2-AR signaling significantly influences MDSC frequency and survival in tumors and other tissues, modulates their expression of immunosuppressive molecules such as arginase-I and PDL-1 and alters their ability to suppress the proliferation of T cells. The regulatory functions of β-AR signaling in MDSCs were found to be dependent upon STAT3 phosphorylation. Moreover, we observed that the β2-AR-mediated increase in survival of MDSCs is dependent upon Fas-FasL interactions, and this is consistent with gene expression analyses which reveal a greater expression of apoptosis-related genes in β2-AR-/- MDSCs. Our data reveals the potential of β2-AR signaling to increase the generation of MDSCs from both murine and human peripheral blood cells and that the immunosuppressive function of MDSCs could be mitigated by treatment with β-AR antagonists, or enhanced by β-AR agonists, strongly supporting the possibility that reducing stress-induced activation of β2-ARs could help to overcome immune suppression and enhance the efficacy of immunotherapy and other cancer therapies.
Current status and application of lactic acid bacteria in animal production systems with a focus on bacteria from honey bee colonies

Lactic acid bacteria (LAB) are widely distributed in nature and, due to their beneficial effects on the host, are used as probiotics. This review describes the applications of LAB in animal production systems such as beekeeping, poultry, swine and bovine production, particularly as probiotics used to improve health, enhance growth and reproductive performance. Given the importance of honeybees in nature and the beekeeping industry as a producer of healthy food worldwide, the focus of this review is on the coexistence of LAB with honeybees, their food and environment. The main LAB species isolated from the beehive and their potential technological use are described. Evidence is provided that 43 LAB bacteria species have been isolated from beehives, of which 20 showed inhibition against 28 species of human and animal pathogens, some of which are resistant to antibiotics. Additionally, the presence of LAB in the beehive and their relationship with antibacterial properties of honey and pollen is discussed. Finally, we describe the use of lactic bacteria from bee colonies and their antimicrobial effect against foodborne pathogens and human health. This review broadens knowledge by highlighting the importance of honeybee colonies as suppliers of LAB and functional food.