Miracle-dz/UniFAR-FTUs huggingface dataset:
Protective Effect of Thymosin β4 against Abdominal Aortic Ischemia–Reperfusion-Induced Acute Lung Injury in Rats

Background and objectives: Ischemia–reperfusion (IR) caused by infrarenal abdominal aorta cross-clamping is an important factor in the development of ischemia–reperfusion injury in various distant organs. Materials and Methods: We investigated potential antioxidant/anti-inflammatory effects of thymosin beta 4 (Tβ4) in a rat model of abdominal aortic surgery-induced IR. Tβ4 (10 mg/kg, intravenous (i.v.)) was administered to rats with IR (90-min ischemia, 180-min reperfusion) at two different periods. One group received Tβ4 1 h before ischemia, and the other received 15 min before the reperfusion period. Results: Results were compared to control and non-Tβ4-treated rats with IR. Serum, bronchoalveolar lavage fluid and lung tissue levels of oxidant parameters were higher, while antioxidant levels were lower in the IR group compared to control. IR also increased inflammatory cytokine levels. Tβ4 reverted these parameters in both Tβ4-treated groups compared to the untreated IR group. Conclusions: Since there is no statistical difference between the prescribed results of both Tβ4-treated groups, our study demonstrates that Tβ4 reduced lung oxidative stress and inflammation following IR and prevented lung tissue injury regardless of timing of administration.
Advance in the Management of Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation

Coagulopathy commonly occurs in sepsis as a critical host response to infection that can progress to disseminated intravascular coagulation (DIC) with an increased mortality. Recent studies have further defined factors responsible for the thromboinflammatory response and intravascular thrombosis, including neutrophil extracellular traps, extracellular vesicles, damage-associated molecular patterns, and endothelial glycocalyx shedding. Diagnosing DIC facilitates sepsis management, and is associated with improved outcomes. Although the International Society on Thrombosis and Haemostasis (ISTH) has proposed criteria for diagnosing overt DIC, these criteria are not suitable for early detection. Accordingly, the ISTH DIC Scientific Standardization Committee has proposed a new category termed “sepsis-induced coagulopathy (SIC)” to facilitate earlier diagnosis of DIC and potentially more rapid interventions in these critically ill patients. Therapy of SIC includes both treatment of the underlying infection and correcting the coagulopathy, with most therapeutic approaches focusing on anticoagulant therapy. Recently, a phase III trial of recombinant thrombomodulin was performed in coagulopathic patients. Although the 28-day mortality was improved by 2.6% (absolute difference), it did not reach statistical significance. However, in patients who met entry criteria for SIC at baseline, the mortality difference was approximately 5% without increased risk of bleeding. In this review, we discuss current advances in managing SIC and DIC.
Retrospective evaluation of healthcare utilisation and mortality of two post-discharge care programmes in Singapore

Objective To evaluate the impact on healthcare utilisation frequencies and charges, and mortality of a programme for frequent hospital utilisers and a programme for patients requiring high acuity post-discharge care as part of an integrated healthcare model. Design A retrospective quasi-experimental study without randomisation where patients who received post-discharge care interventions were matched 1:1 with unenrolled patients as controls. Setting The National University Health System (NUHS) Regional Health System (RHS), which was one of six RHS in Singapore, implemented the NUHS RHS Integrated Interventions and Care Extension (NICE) programme for frequent hospital utilisers and the NUHS Transitional Care Programme (NUHS TCP) for high acuity post-discharge care. The programmes were supported by the Ministry of Health in Singapore, which is a city-state nation located in Southeast Asia with a 5.6 million population. Participants Linked healthcare administrative data, for the time period of January 2013 to December 2016, were extracted for patients enrolled in NICE (n=554) or NUHS TCP (n=270) from June 2014 to December 2015, and control patients. Interventions For both programmes, teams conducted follow-up home visits and phone calls to monitor and manage patients’ post-discharge. Primary outcome measures One-year pre- and post-enrolment healthcare utilisation frequencies and charges of all-cause inpatient admissions, emergency admissions, emergency department attendances, specialist outpatient clinic (SOC) attendances, total inpatient length of stay and mortality rates were compared. Results Patients in NICE had lower mortality rate, but higher all-cause inpatient admission, emergency admission and emergency department attendance charges. Patients in NUHS TCP did not have lower mortality rate, but had higher emergency admission and SOC attendance charges. Conclusions Both NICE and NUHS TCP had no improvements in 1 year healthcare utilisation across various setting and metrics. Singular interventions might not be as impactful in effecting utilisation without an overhauling transformation and restructuring of the hospital and healthcare system.
Maximum-likelihood estimation of the entropy of an attractor.

In this paper, a maximum-likelihood estimate of the (Kolmogorov) entropy of an attractor is proposed that can be obtained directly from a time series. Also, the relative standard deviation of the entropy estimate is derived; it is dependent on the entropy and on the number of samples used in the estimation.
The Impact of Dairy Products in the Development of Type 2 Diabetes: Where Does the Evidence Stand in 2019?

ABSTRACT The prevalence of type 2 diabetes (T2D) has increased rapidly. Adopting a heathy diet is suggested as one of the effective behaviors to prevent or delay onset of T2D. Dairy consumption has been recommended as part of a healthy diet, but there remains uncertainty in both the scientific community and the public about the effect of different dairy products on T2D risk. In a recent workshop, the evidence on dairy products and T2D risk was presented and discussed by a group of experts. The main conclusions from the workshop are presented in this position paper and are as follows. 1) Available evidence from large prospective cohort studies and limited randomized controlled trials (RCTs) suggests that total dairy consumption has a neutral or moderately beneficial effect on T2D risk. 2) Increasing evidence from prospective cohort studies indicates that yogurt is most strongly associated with a lower T2D risk, but evidence from RCTs is scarce. 3) Fatty acids from dairy (medium-chain, odd, and very long-chain SFAs as well as trans-palmitoleic acid) are associated with lower T2D risk and improved metabolic health, but more research is needed on studies that explore cause and effect relations to exclude the possibility that the dairy fatty acids simply serve as markers of overall dairy consumption. 4) The food matrix can be a stronger determinant of health effects than SFA content. This review further identifies research gaps in the existing knowledge and highlights key research questions that need to be addressed to better understand the impact of dairy consumption on future T2D risk.
Cerebrospinal fluid neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case–control studies

Objective Neurofilament is a biomarker of axonal injury proposed as a useful adjunct in the monitoring of patients with multiple sclerosis (MS). We conducted a systematic review and meta-analysis of case–control studies that have measured neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of people with MS (pwMS), in order to determine whether, and to what degree, CSF NfL levels differentiate MS from controls, or the subtypes or stages of MS from each other. Methods Guidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. Electronic databases were searched for published and ‘grey’ literature, with 151 hits. Of 51 full articles screened, 20 were included in qualitative analysis, and 14 in meta-analysis. Results CSF NfL was higher in 746 pwMS than 435 (healthy and disease) controls, with a moderate effect size of 0.61 (p < 0.00001). Mean CSF NfL levels were significantly higher in 176 pwMS with relapsing disease than 92 with progressive disease (2124.8 ng/L, SD 3348.9 vs 1121.4 ng/L, SD 947.7, p = 0.0108). CSF NfL in 138 pwMS in relapse (irrespective of MS subtype) was double that seen in 268 pwMS in remission (3080.6 ng/L, SD 4715.9 vs 1541.7 ng/L, SD 2406.5, p < 0.0001). Conclusions CSF NfL correlates with MS activity throughout the course of MS, reflecting the axonal damage in pwMS. Relapse is more strongly associated with elevated CSF NfL levels than the development of progression, and NfL may be most useful as a marker of disease ‘activity’ rather than as a marker of disability or disease stage.
Pain correlates with social integration in individuals with traumatic spinal cord injury: A cross-sectional survey.

OBJECTIVE To describe the relationship between pain and social integration following spinal cord injury using comprehensive evaluation of pain-related clinical characteristics and different aspects of social integration. DESIGN A cross-sectional study. PARTICIPANTS A total of 318 participants with American Spinal Cord Injury Association Impairment Scale (AIS) Grades A, B, C or D and > 3 months post-injury. METHODS All participants completed the survey relating to demographics, pain characteristics, and the Craig Handicap Assessment Reporting Technique Social Integration scores. RESULTS Individuals who were younger, those 3-6 years after injury, and those with a grade of AIS grade A (odds ratio (OR) 8.32, 95% confidence interval (95% CI) 1.83-12.07) or B (OR 3.25, 95% CI 0.91-7.63) were more likely to report neuropathic pain. Significant inverse correlations were found between pain intensity and social integration (R = -0.597, p = 0.019). Brief Pain Inventory interference scores were negatively associated with 5 (friends, living situation, business, strangers and family) of 6 domains of Craig Handicap Assessment Reporting Technique social integration (p < 0.001). Pain type and only 1 domain (strangers) showed a significant negative relationship (B=-1.47, p = 0.02). CONCLUSION Chronic pain after spinal cord injury is negatively associated with Craig Handicap Assessment Reporting Technique social integration. Brief Pain Inventory Pain interference, to a greater extent than pain type, best predicts social integration after spinal cord injury.
Potential Molecular Mechanisms of AURKB in the Oncogenesis and Progression of Osteosarcoma Cells: A Label-Free Quantitative Proteomics Analysis

Our previous study indicated that knockdown of Aurora-B inhibit the proliferation of osteosarcoma cells. But the function and molecular mechanisms of Aurora-B in osteosarcoma cells growth and metastasis remains unclear. The aim of this study was to investigate the molecular mechanisms of Aurora-B in the progression of osteosarcoma. Osteosarcoma cells (U2-OS and 143B) were treated with specific Lentivirus-Vectors (up or downregulation Aurora-B). The ability of cells proliferation, migration, and invasion was measured using Cell-Counting Kit-8, wound healing and transwell invasion assays. Furthermore, based on label-free quantitative proteomic analysis of potential molecular mechanisms of Aurora-B in human 143B cells. A total of 25 downregulated and 76 upregulated differentially expressed proteins were screened in terms of the change in their expression abundance. We performed functional annotation and functional enrichment analyses. Gene ontology enrichment, KEGG analysis, and protein–protein interaction networks were constructed and analyzed. We found that the PTK2 may play an important role in the progression of osteosarcoma cells. Finally, Western blot revealed that expression of PTK2, AKT, PI3K, and nuclear factor-kappaB increased after over expression of Aurora-B. Overall, these data highlight that Aurora-B may promote the malignant phenotype of osteosarcoma cells by activating the PTK2/PI3K/AKt/nuclear factor-KappaB pathway.
Risk Perceptions of People Living with HIV/AIDS

Little as known about how people living with HIV/AIDS (PLWH/A) assess their vulnerability to non-HIVrelated risk factors, and how this judgement is affected by perceived similarity with others. This study indicates not only that PLWH/A are optimistically biased in their risk pereceptions, but also that they do not use others' HIV status to assess similarity. Perceived similarity with others, however, affects risk judgements: greater the perceived similarity with others, greater the tendency to judge others' vulnerability relative to one's own. Findings point to the importance of considering similarity as a key variable in understanding how risk assessments are made by persons with chronic health conditions.
New symptoms identified in phytoplasma-infected plants reveal extra stages of pathogen-induced meristem fate-derailment.

In flowering plants, the transition of a shoot apical meristem from vegetative to reproductive destiny is a graduated, multi-stage process that involves sequential conversion of the vegetative meristem to an inflorescence meristem, initiation of floral meristems, emergence of flower organ primordia, and formation of floral organs. This orderly process can be derailed by phytoplasma, a bacterium that parasitizes phloem sieve cells. In a previous study, we showed that phytoplasma-induced malformation of flowers reflects stage-specific derailment of shoot apical meristems from their genetically preprogrammed reproductive destiny. Our current study unveiled new symptoms of abnormal morphogenesis, pointing to derailment of meristem transition at additional stages previously unidentified. We also found that the fate of developing meristems may be derailed even after normal termination of the floral meristem and onset of seed production. While previous reports by others have indicated that different symptoms may be induced by different phytoplasmal effectors, the phenomenon observed in our experiment raises interesting questions as to (i) whether effectors can act at specific stages of meristem transition, and (ii) whether specific floral abnormalities are attributable to meristem fate-derailment events triggered by different effectors that each act at a specific stage in meristem transition. Research addresses such questions may lead to discoveries of an array of phytoplasmal effectors.
Higher Fatality for Severe Fever with Thrombocytopenia Syndrome Complicated by Hemophagocytic Lymphohistiocytosis

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious zoonosis caused by the SFTS virus. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome associated with excessive immune activation. Cytokine storms are often seen in both SFTS and HLH, resulting in rapid disease progression and poor prognosis. The aim of this study was to identify whether SFTS cases complicated by HLH are related to higher rates of mortality. Descriptive analysis of the frequency of clinical and laboratory data, complications, treatment outcomes, and HLH-2004 criteria was performed. Cases presenting with five or more clinical or laboratory findings corresponding to the HLH-2004 diagnostic criteria were defined as SFTS cases complicated by HLH. Eighteen cases of SFTS were identified during a 2-year study period, with a case-fatality proportion of 22.2% (4 among 18 cases, 95% confidence interval 9%–45.2%). SFTS cases complicated by HLH were identified in 33.3% (6 among 18 cases). A mortality rate of 75% (3 among 4 cases) was recorded among SFTS cases complicated by HLH. Although there were no statistically significant differences in outcomes, fatal cases exhibited more frequent correlation with HLH-2004 criteria than non-fatal cases [3/14 (21.4%) vs. 3/4 (75%), p=0.083]. In conclusion, the present study suggests the possibility that SFTS cases complicated by HLH are at higher risk of poor prognosis.
Computational Simulation of Adapter Length-Dependent LASSO Probe Capture Efficiency

Multiplexed cloning of long DNA sequences is a valuable technique in many biotechnology applications, such as long-read genome sequencing and the creation of open reading frame (ORF) libraries. Long-adapter single-stranded oligonucleotide (LASSO) probes have shown promise as a tool to clone long DNA fragments. LASSO probes are molecular inversion probes (MIP) engineered with an adapter region of user-defined length, flanked between template-specific probe sequences. Herein, we demonstrate that the adapter length is a key feature of LASSO that influences the efficiency of gene capture and cloning. Furthermore, we applied a model based on Monte Carlo molecular simulation in order to study the relationship between the long-adapter length of LASSO and capture enrichment. Our results suggest that the adapter length is a factor that contributes to the free energy of target–probe interaction, thereby determining the efficiency of capture. The results indicate that LASSOs with extremely long adapters cannot capture the targets well. They also suggest that targets of different lengths may prefer adapters of different lengths.
Cytochrome C Oxidase Subunit 1, Internal Transcribed Spacer 1, Nicotinamide Adenine Dinucleotide Hydrogen Dehydrogenase Subunits 2 and 5 of Clonorchis sinensis Ancient DNA Retrieved from Joseon Dynasty Mummy Specimens

We analyzed Clonorchis sinensis ancient DNA (aDNA) acquired from the specimens of the Joseon mummies. The target regions were cytochrome C oxidase subunit 1 (CO1), internal transcribed spacer 1 (ITS1), nicotinamide adenine dinucleotide hydrogen (NADH) dehydrogenase subunits 2 (NAD2) and 5 (NAD5). The sequences of C. sinensis aDNA was completely or almost identical to modern C. sinensis sequences in GenBank. We also found that ITS1, NAD2 and NAD5 could be good markers for molecular diagnosis between C. sinensis and the other trematode parasite species. The current result could improve our knowledge about genetic history of C. sinensis.
Dynamic expression patterns of 6‐O endosulfatases during zebrafish development suggest a subfunctionalisation event for sulf2

The 6‐O‐endosulfatase enzymes (Sulfs) edit the final sulfation pattern and function of heparan sulfate (HS) by removal of 6‐O‐sulfate groups from the chain. To date, two mammalian sulf genes have been identified that regulate many signalling pathways during embryonic development. In zebrafish a sulf1 ortholog and duplicate copies of the mammalian sulf2 gene, sulf2a and sulf2, have been identified, which contain conserved motifs characteristic of vertebrate sulf genes. Zebrafish sulf1 and sulf2a are broadly expressed in the central nervous system (CNS) and non‐neuronal tissue including heart, somite boundaries, olfactory system, and otic vesicle, whereas sulf2 expression is almost entirely restricted to the CNS. The duplicate copies of sulf2 have distinct expression patterns, which together mirror that of mouse sulf2, suggesting duplication in the teleost lineage has been followed by subfunctionalisation, whereby both genes need to be preserved by selection to ensure the ancestral gene's expression profile and function is maintained. Developmental Dynamics 239:3312–3323, 2010. © 2010 Wiley‐Liss, Inc.
Analysis of A47, an Immunoprevalent Protein of Vaccinia Virus, Leads to a Reevaluation of the Total Antiviral CD8+ T Cell Response

ABSTRACT Vaccinia virus (VACV) is the prototypic orthopoxvirus and was the live vaccine used to eradicate smallpox. In addition, VACV is a possible vector for recombinant vaccines. Despite these reasons for study, the roles of many VACV genes are unknown, and some fundamental aspects, such as the total size of immune responses, remain poorly characterized. VACV gene A47L is of interest because it is highly transcribed, has no sequence similarity to any nonpoxvirus gene, and contains a larger-than-expected number of CD8+ T cell epitopes. Here it is shown that A47L is not required for growth in vitro and does not contribute to virulence in mice. However, we confirmed that this one protein primes CD8+ T cells to three different epitopes in C57BL/6 mice. In the process, one of these epitopes was redefined and shown to be the most dominant in A47 and one of the more highly ranked in VACV as a whole. The relatively high immunogenicity of this epitope led to a reevaluation of the total CD8+ T cell response to VACV. By the use of two methods, the true size of the response was found to be around double previous estimates and at its peak is on the order of 60% of all CD8+ T cells. We speculate that more CD8+ T cell epitopes remain to be mapped for VACV and that underestimation of responses is unlikely to be unique to VACV, so there would be merit in revisiting this issue for other viruses.
Expansion and Functional Divergence of Inositol Polyphosphate 5-Phosphatases in Angiosperms

Inositol polyphosphate 5-phosphatase (5PTase), a key enzyme that hydrolyzes the 5′ position of the inositol ring, has essential functions in growth, development, and stress responses in plants, yeasts, and animals. However, the evolutionary history and patterns of 5PTases have not been examined systematically. Here, we report a comprehensive molecular evolutionary analysis of the 5PTase gene family and define four groups. These four groups are different from former classifications, which were based on in vitro substrate specificity. Most orthologous groups appear to be conserved as single or low-copy genes in all lineages in Groups II–IV, whereas 5PTase genes in Group I underwent several duplication events in angiosperm, resulting in multiple gene copies. Whole-genome duplication (WGD) was the main mechanism for 5PTase duplications in angiosperm. Plant 5PTases have more members than that of animals, and most plant 5PTase genes appear to have evolved under strong purifying selection. The paralogs have diverged in substrate specificity and expression pattern, showing evidence of selection pressure. Meanwhile, the increase in 5PTases and divergences in sequence, expression, and substrate might have contributed to the divergent functions of 5PTase genes, allowing the angiosperms to successfully adapt to a great number of ecological niches.
Paralogs of the C-Terminal Domain of the Cyanobacterial Orange Carotenoid Protein Are Carotenoid Donors to Helical Carotenoid Proteins1[OPEN]

The cyanobacterial CTDHs, homodimers sharing one carotenoid molecule, are capable of taking the carotenoid from membranes and easily giving it to other proteins. The photoactive Orange Carotenoid Protein (OCP) photoprotects cyanobacteria cells by quenching singlet oxygen and excess excitation energy. Its N-terminal domain is the active part of the protein, and the C-terminal domain regulates the activity. Recently, the characteristics of a family of soluble carotenoid-binding proteins (Helical Carotenoid Proteins [HCPs]), paralogs of the N-terminal domain of OCP, were described. Bioinformatics studies also revealed the existence of genes coding for homologs of CTD. Here, we show that the latter genes encode carotenoid proteins (CTDHs). This family of proteins contains two subgroups with distinct characteristics. One CTDH of each clade was further characterized, and they proved to be very good singlet oxygen quenchers. When synthesized in Escherichia coli or Synechocystis PCC 6803, CTDHs formed dimers that share a carotenoid molecule and are able to transfer their carotenoid to apo-HCPs and apo-OCP. The CTDHs from clade 2 have a cysteine in position 103. A disulfide bond is easily formed between the monomers of the dimer preventing carotenoid transfer. This suggests that the transfer of the carotenoid could be redox regulated in clade 2 CTDH. We also demonstrate here that apo-OCPs and apo-CTDHs are able to take the carotenoid directly from membranes, while HCPs are unable to do so. HCPs need the presence of CTDH to become holo-proteins. We propose that, in cyanobacteria, the CTDHs are carotenoid donors to HCPs.