Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical utility of serum fucosylated fraction of alpha-fetoprotein in the diagnostic of hepatocellular carcinoma: a comprehensive analysis with large sample size

We conducted a comprehensive meta-analysis of the utility of AFP-L3 for the diagnosis of hepatocellular carcinoma, to provide a more accurate estimation for the clinical utility of AFP-L3. We performed online searches in five databases (PubMed, China National Knowledge Infrastructure, Wanfang, Web of Science, and Embase), from inception to December 31, 2021. Pooled sensitivity, specificity, and area under the curve (AUC) with the matching 95% confidence intervals (95% CIs) were calculated to estimate the diagnostic value of AFP-L3. Thirty-four studies were included in the meta-analysis. The pooled sensitivity was 0.70 [95% confidence interval (CI): 0.63–0.77], and the specificity was 0.91 (95% CI: 0.88–0.94). The estimated area under the curve (AUC) was 0.90 (95% CI: 0.87–0.92). The positive likelihood ratio and negative likelihood ratio were 7.78 (95% CI: 5.7–10.7) and 0.33 (95% CI: 0.26–0.41), respectively. The diagnostic odds ratio was 24 (95% CI: 16–37). The subgroup analysis indicated moderate sensitivity (0.79) and high specificity (0.89) for the Asian population (AUC = 0.89), and similar specificity (0.95) but lower sensitivity (0.35) for Caucasians (AUC = 0.80). Deeks’ funnel plot asymmetry test detected no publication bias (P = 0.460). The sensitivity analysis showed that the pooled results were stable. Taken together, our results indicated that AFP-L3 demonstrates high diagnostic ability for HCC, especially among Asian populations. AFP-L3 is a useful means for high-volume screening, which can help doctors optimize diagnosis workflow, reduce workload, and improve detection sensitivity. The combination of multiple biomarkers may provide more accurate diagnostic tools for HCC in the future.
Bacillus-supplemented diet improves growth performance in Jeju native pigs by modulating myogenesis and adipogenesis

Abstract Probiotics are used in pigs as nutritional supplements to improve health and induce the development of muscle and adipose tissue for enhancing growth performance and harvesting quality meat. In this study, we investigated the effects of Bacillus-based probiotic supplementation on the physiological and biochemical changes in Jeju native pigs (JNPs), including growth performance, backfat layers, blood parameters, serum IgG levels, myogenic and adipogenic markers, and expression of inflammatory markers. Average daily gain and feed efficiency were higher in the Bacillus diet group than in the basal diet group, while backfat thickness was lower in the Bacillus diet group than in the basal diet group. Blood biochemical parameters and hematological profiles were not altered significantly by Bacillus-based probiotic supplementation. Serum IgG concentration increased in the Bacillus diet group compared to the basal diet group. The Bacillus diet group showed increased adipogenic and myogenic markers expression in the longissimus dorsi muscle and adipose tissues. Overall, the data suggest that the Bacillus-based probiotics-supplemented diet regulates myogenesis and adipogenesis in JNPs and improves growth performance. We postulate that this may be due to the changes in the gut microbiota of pigs due to probiotic supplementation.
Leptospira interrogans Aer2: an Unusual Membrane-Bound PAS-Heme Oxygen Sensor

Leptospira interrogans, the cause of the zoonotic infection leptospirosis, is found in soil and water contaminated with animal urine. L. interrogans survives in complex environments with the aid of 12 chemoreceptors, none of which has been explicitly studied. In this study, we characterized the first L. interrogans chemoreceptor, LiAer2, and reported its unique characteristics. LiAer2 is membrane-bound, has three cytoplasmic PAS-heme domains that each bound hexacoordinate b-type heme and O2 turned LiAer2 signaling off. ABSTRACT In this study, we provide the first characterization of a chemoreceptor from Leptospira interrogans, the cause of leptospirosis. This receptor is related to the Aer2 receptors that have been studied in other bacteria. In those organisms, Aer2 is a soluble receptor with one or two PAS-heme domains and signals in response to O2 binding. In contrast, L. interrogans Aer2 (LiAer2) is an unusual membrane-bound Aer2 with a periplasmic domain and three cytoplasmic PAS-heme domains. Each of the three PAS domains bound b-type heme via conserved Eη-His residues. They also bound O2 and CO with similar affinities to each other and other PAS-heme domains. However, all three PAS domains were uniquely hexacoordinate in the deoxy-heme state, whereas other Aer2-PAS domains are pentacoordinate. Similar to other Aer2 receptors, LiAer2 could hijack the E. coli chemotaxis pathway but only when it was expressed with an E. coli high-abundance chemoreceptor. Unexpectedly, the response was inverted relative to classic Aer2 receptors. That is, LiAer2 caused E. coli to tumble (it was signal-on) in the absence of O2 and to stop tumbling in its presence. Thus, an endogenous ligand in the deoxy-heme state was correlated with signal-on LiAer2, and its displacement for gas-binding turned signaling off. This response also occurred in a soluble version of LiAer2 lacking the periplasmic domain, transmembrane (TM) region, and first two PAS domains, meaning that PAS3 alone was sufficient for O2-mediated control. Future studies are needed to understand the unique signaling mechanisms of this unusual Aer2 receptor. IMPORTANCE Leptospira interrogans, the cause of the zoonotic infection leptospirosis, is found in soil and water contaminated with animal urine. L. interrogans survives in complex environments with the aid of 12 chemoreceptors, none of which has been explicitly studied. In this study, we characterized the first L. interrogans chemoreceptor, LiAer2, and reported its unique characteristics. LiAer2 is membrane-bound, has three cytoplasmic PAS-heme domains that each bound hexacoordinate b-type heme and O2 turned LiAer2 signaling off. An endogenous ligand in the deoxy-heme state was correlated with signal-on LiAer2 and its displacement for O2-binding turned signaling off. Our study corroborated previous findings that Aer2 receptors are O2 sensors, but also demonstrated that they do not all function the same way.
Surveying the Epigenetic Landscape of Tuberculosis in Alveolar Macrophages

Tuberculosis (TB) remains the leading cause of bacterial disease-related death and is among the top 10 overall causes of death worldwide. The complex nature of this infectious lung disease has proven difficult to treat, and significant research efforts are now evaluating the feasibility of host-directed, adjunctive therapies. ABSTRACT Tuberculosis (TB) remains the leading cause of bacterial disease-related death and is among the top 10 overall causes of death worldwide. The complex nature of this infectious lung disease has proven difficult to treat, and significant research efforts are now evaluating the feasibility of host-directed, adjunctive therapies. An attractive approach in host-directed therapy targets host epigenetics, or gene regulation, to redirect the immune response in a host-beneficial manner. Substantial evidence exists demonstrating that host epigenetics are dysregulated during TB and that epigenetic-based therapies may be highly effective to treat TB. However, the caveat is that much of the knowledge that exists on the modulation of the host epigenome during TB has been gained using in vitro, small-animal, or blood-derived cell models, which do not accurately reflect the pulmonary nature of the disease. In humans, the first and major target cells of Mycobacterium tuberculosis are alveolar macrophages (AM). As such, their response to infection and treatment is clinically relevant and ultimately drives the outcome of disease. In this review, we compare the fundamental differences between AM and circulating monocyte-derived macrophages in the context of TB and summarize the recent advances in elucidating the epigenomes of these cells, including changes to the transcriptome, DNA methylome, and chromatin architecture. We will also discuss trained immunity in AM as a new and emerging field in TB research and provide some perspectives for the translational potential of targeting host epigenetics as an alternative TB therapy.
Registered nurses’ approach to pressure injury prevention: A descriptive qualitative study

Abstract Aims To explore Registered Nurses' approaches to pressure injury prevention, including how they perceive their roles, how they prioritize pressure injury prevention and factors influencing prevention in the Chinese context. Design A qualitative descriptive study. Methods Audio‐recorded, face‐to‐face, semi‐structured individual interviews were conducted with Registered Nurses in a large tertiary hospital in China from August to December 2020. Using the System Engineering Initiative for Patient Safety Model, the interview guide was developed to describe the work system, processes and outcomes (three domains) associated with nurses' pressure injury prevention practices. Deductive and inductive content analyses were used. Findings Twenty‐seven nurses participated in the interviews. Four themes related to two domains of the model emerged: Work system: (i) Nurses lead and coordinate pressure injury prevention; Work processes: (ii) Individualized pressure injury prevention is founded on comprehensive patient assessment; (iii) Collaborating ensures patients receive appropriate pressure injury prevention; and (iv) Competing factors influence the delivery of appropriate pressure injury prevention. One category emerged about work outcome: Nurses strive to do their best in pressure injury prevention but hold major concerns when pressure injuries occur. Conclusions Nurses play a leading role in pressure injury prevention delivery but require appropriate resources and assistance and support from other healthcare personnel, patients and carers. Understaffing, lack of resources, complex reporting and poor patient compliance challenge nurses in their delivery of pressure injury prevention. Impact Pressure injury prevention is primarily a nursing responsibility therefore nurses' approaches to prevention were explored. Nurses rely on collaboration with others and access to various resources to provide pressure injury prevention. They recognize the patients' and carers' roles and acknowledge the importance of accessing guidance and support from nursing leaders and wound experts. Acknowledging nurses leading role in prevention and ensuring they have adequate resources are important for quality care.
FTO gene polymorphisms and hepatoblastoma susceptibility among Chinese children

ABSTRACT Current knowledge on the etiology of hepatoblastoma remains limited. FTO gene has been documented as a susceptibility gene for several types of cancer. However, its role has not been characterized in hepatoblastoma. Herein, we intended to explore whether FTO gene single nucleotide polymorphisms (SNPs) contribute to the risk of hepatoblastoma. A multi-center case–control study was conducted including 358 cases and 1512 controls recruited from the night hospitals in China. Odds ratios (ORs) and 95% confidence intervals (CIs), for the association of FTO gene SNPs with hepatoblastoma risk, were estimated using conditional logistic regression models, adjusted for relevant confounding variables. Four SNPs (rs1477196 G > A, rs9939609 T > A, rs7206790 C > G, and rs8047395 A > G) in the FTO gene were genotyped. We detected a significant association between rs9939609 T > A and decreased risk of hepatoblastoma (TA vs. TT: adjust OR = 0.73, 95% CI = 0.54–0.99, P = 0.041; TA/AA vs. TT: adjust OR = 0.73, 95% CI = 0.55–0.97, P = 0.032). Compared to 0–3 protective genotypes, carriers with four protective genotypes showed enough strength to protect from hepatoblastoma (adjust OR = 0.65, 95% CI = 0.47–0.91, P = 0.012). In stratification analysis, we also detected a significantly decreased risk of hepatoblastoma in subjects with rs9939609 TA/AA or with four protective genotypes in some subgroups. Our results provided some clues for an association of FTO gene SNPs with hepatoblastoma risk in Chinese children. Abbreviations: GWAS, genome-wide association study; FTO, The fat mass and obesity-associated gene; SNP, single nucleotide polymorphism; m6A, N6-methyladenosine; mRNA, messenger RNA; LD, linkage disequilibrium; HWE, Hardy-Weinberg equilibrium; OR, odds ratio; CI, confidence interval; AML, acute myeloid leukemia; GSC, glioblastoma stem(-like) cell; HER2, human epidermal growth factor receptor 2.
Extraction of Electronic Health Record Data using Fast Healthcare Interoperability Resources for Automated Breast Cancer Risk Assessment

Women at high risk for breast cancer may benefit from enhanced screening and risk-reduction strategies. However, limited time during clinical encounters is one barrier to routine breast cancer risk assessment. We evaluated if electronic health record (EHR) data downloaded using Fast Healthcare Interoperability Resources (FHIR) is sufficient for breast cancer risk calculation in our decision support tools, RealRisks and BNAV. We accessed EHR data using FHIR for six patient advocates, and downloaded and parsed XML documents. We searched for relevant clinical variables, and evaluated if data was sufficient to calculate risk using validated models (Gail, Breast Cancer Screening Consortium [BCSC], BRCAPRO). While only one advocate had sufficient EHR data to calculate risk using the BCSC model only, we identified variables including age, race/ethnicity, mammographic density, and prior breast biopsy in most advocates. EHR data from FHIR could be incorporated into automated breast cancer risk calculation in clinical decision support tools.
Attenuation of glutamine synthetase selection marker improves product titer and reduces glutamine overflow in Chinese hamster ovary cells

The glutamine synthetase (GS) expression system is commonly used to ensure stable transgene integration and amplification in Chinese hamster ovary (CHO) host lines. Transfected cell populations are typically grown in the presence of the GS inhibitor, methionine sulfoximine (MSX), to further select for increased transgene copy number. However, high levels of GS activity produce excess glutamine. We hypothesized that attenuating the GS promoter while keeping the strong IgG promoter on the GS‐IgG expression vector would result in a more efficient cellular metabolic phenotype. Herein, we characterized CHO cell lines expressing GS from either an attenuated promoter or an SV40 promoter and selected with/without MSX. CHO cells with the attenuated GS promoter had higher IgG specific productivity and lower glutamine production compared to cells with SV40‐driven GS expression. Selection with MSX increased both specific productivity and glutamine production, regardless of GS promoter strength. 13C metabolic flux analysis (MFA) was performed to further assess metabolic differences between these cell lines. Interestingly, central carbon metabolism was unaltered by the attenuated GS promoter while the fate of glutamate and glutamine varied depending on promoter strength and selection conditions. This study highlights the ability to optimize the GS expression system to improve IgG production and reduce wasteful glutamine overflow, without significantly altering central metabolism. Additionally, a detailed supplementary analysis of two “lactate runaway” reactors provides insight into the poorly understood phenomenon of excess lactate production by some CHO cell cultures.
A meta-analysis of the determinants of patient satisfaction and loyalty

Abstract In the contemporary competitive environment, healthcare providers have had to ensure that their customers are satisfied with the quality of medical service they receive as this is critical in customer retention and their repeated use of the service of the healthcare provider. Taking the patient's perspective, several studies have attempted to identify the determinants of patient satisfaction and their loyalty toward healthcare providers. Studies have yielded mixed results and to get a clearer understanding of these relationships, we perform a meta-analysis of 13 studies to test nine hypotheses. We discuss the implications of the results.
Evidence of Biological Mechanisms and Health Predictions: An Insight into Clinical Reasoning

ABSTRACT:Traditionally, the understanding of biological mechanisms has played a central role in clinical reasoning. With the rise of the evidence-based paradigm, however, this role has come under scrutiny. On the one hand, clinical guidelines now place less emphasis on the evidence of pathophysiological mechanisms, a shift motivated by the unreliability of our understanding of complex biological mechanisms. On the other hand, some scholars defend evidence of mechanisms as crucial for clinical practice. This article assesses the relevance of evidence of biological mechanisms in two types of clinical predictions: predictions about the efficacy and about the safety of a certain intervention for a particular patient. For each type of prediction, the article analyzes the two roles that evidence of mechanisms might have—confirming and disconfirming—depending on whether the evidence supports that certain epidemiological results apply to the single patient. The analysis shows that the “unreliability because of incompleteness” argument against the emphasis on mechanistic clinical thinking only applies to some of the considered cases. The article concludes by offering a model for a more granular view of the role that evidence of mechanisms should play in clinical practice.
Registry data analysis of hematopoietic stem cell transplantation on systemic chronic active Epstein–Barr virus infection patients in Japan

The effects of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) on systemic chronic active Epstein–Barr virus infection (sCAEBV) are yet to be analyzed in a large number of patients. Using the Japanese registry database, Transplant Registry Unification Management Program, we investigated the outcomes of 102 sCAEBV patients who underwent allo‐HSCT. The median age at HSCT was 21 years, and the three‐year overall survival (3‐year OS) rate was 72.5%. Of the 90 patients whose viral load after allo‐HSCT was evaluated, 56 (62.2%) achieved a virological complete response, defined by the complete resolution of disease activity with a significant decrease in EBV‐DNA in peripheral blood. The multivariate Cox proportional hazard model indicated that advanced age, in adolescents and young adults (AYA) (age, 15–39) and adults (age, ≥40 years) was a risk factor of poor OS. The hazard ratios (HRs) of the AYA and adult groups were 10.87 (95% confidence interval [CI]: 1.98–59.56, p = .006) and 15.93 (95% CI: 2.45–103.8, p = .004), respectively. Disease activity (HR 5.74), elevated soluble IL‐2 receptor (sIL‐2R) (≥ median, 691 U/mL) at HSCT (HR 6.93), and conditioning without radiotherapy (HR 3.53) were also independently associated with poor survival. Notably, 79% of radiotherapy doses were less than 6 Gy. Regardless of the presence of hemophagocytic lymphohistiocytosis, the group with a high sIL‐2R level (≥2000 U/mL) showed a poorer prognosis. Although allo‐HSCT is the only curative therapy for sCAEBV, treatment strategies need to be improved for high‐risk patients, especially those with high levels of sIL‐2R.
Interactions and Stability of Gut Microbiota in Zebrafish Increase with Host Development

Understanding gut microbial stability and the underlying mechanisms is an important but largely ignored ecological issue in vertebrate fish. Here, using a zebrafish model and network analysis of the gut microbiota we found that microbial interactions and stability in the gut ecosystem increase with fish development. ABSTRACT Understanding interactions within the gut microbiome and its stability are of critical importance for deciphering ecological issues within the gut ecosystem. Recent studies indicate that long-term instability of gut microbiota is associated with human diseases, and recovery of stability is helpful in the return to health. However, much less is known about such topics in fish, which encompass nearly half of all vertebrate diversity. Here, we examined the assembly and succession of gut microbiota in more than 550 zebrafish, and evaluated the variations of microbial interactions and stability across fish development from larva to adult using molecular ecological network analysis. We found that microbial interactions and stability in the fish gut ecosystem generally increased with host development. This could be attributed to the development of the zebrafish immune system, the increasing amount of space available for microbial colonization within the gut, and the greater stability of nutrients available for the colonized microbiota in adult zebrafish. Moreover, the potential keystone taxa, even those with relatively low abundances, played important roles in affecting the microbial interactions and stability. These findings indicate that regulating rare keystone taxa in adult fish may have great potential in gut microbial management to maintain gut ecosystem stability, which could also provide references for managing gut microbiota in humans and other animals. IMPORTANCE Understanding gut microbial stability and the underlying mechanisms is an important but largely ignored ecological issue in vertebrate fish. Here, using a zebrafish model and network analysis of the gut microbiota we found that microbial interactions and stability in the gut ecosystem increase with fish development. This finding has important implications for microbial management to maintain gut homeostasis and provide better gut ecosystem services for the host. First, future studies should always consider using fish of different age groups to gain a full understanding of gut microbial networks. Second, management of the keystone taxa, even those that are only present at a low abundance, during the adult stage may be a viable pathway to maintain gut ecosystem stability. This study greatly expands our current knowledge regarding gut ecosystem stability in terms of ecological networks affected by fish development, and also highlights potential directions for gut microbial management in humans and other animals.