Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of acute systematic hypoxia on human urinary metabolites using LC-MS-based metabolomics.

AIMS The metabolic variability and response to acute systematic hypoxia have been characterized by the high resolution of liquid chromatography/time-of-flight/mass spectrometry (LC-TOF/MS) in this study. Specifically, we compared the urinary metabolic profiles of six healthy sedentary men under normoxia (21% O2) with acute systematic hypoxic conditions of 12% (equivalent to about 4500 m in altitude) and 15% O2 (equivalent to about 3000 m in altitude) for 2 h in a normobaric hypoxia chamber. RESULTS A clear separation of dose-dependent responses was visualized by Partial Least Squares Discriminant Analysis (PLS-DA) between normoxic and hypoxic conditions. Over one thousand features were found in this study, about 10% of which showed significant change from hypoxia treatment and 26 metabolites were identified; however, there is great variability in metabolite concentrations among the 6 subjects, which reflects the diversity of human systems. Within the variability, we found that 1-methyladenosine and 5-methylthioadenosine are conspicuously upregulated; on the other hand, 3-inodoleacetic acid and L-glutamic acid were downregulated. CONCLUSION The increase in purine metabolic products (uric acid, xanthine, and hypoxathine) results from hypoxia; this increase can be used as a marker for the hypoxic condition. 1-Methyladenosine was also highly upregulated from MH to SH and may be a very sensitive biomarker that reflects cellular hypoxia, due to its potential connection to HIF-1. The increase of free carnitine and acetyl carnitines, on the other hand, signals a change in the pathway of energy, or lipid, metabolism.
Aβ40 modulates GABAA receptor α6 subunit expression and rat cerebellar granule neuron maturation through the ERK/mTOR pathway

In addition to their neurotoxic role in Alzheimer's disease (AD), β‐amyloid peptides (Aβs) are also known to play physiological roles. Here, we show that recombinant Aβ40 significantly increased the outward current of the GABAA receptor containing (GABAAα6) in rat cerebellar granule neurons (CGNs). The Aβ40‐mediated increase in GABAAα6 current was mediated by an increase in GABAAα6 protein expression at the translational rather than the transcriptional level. The exposure of CGNs to Aβ40 markedly induced the phosphorylation of ERK (pERK) and mammalian target of rapamycin (pmTOR). The increase in GABAAα6 current and expression was attenuated by specific inhibitors of ERK or mTOR, suggesting that the ERK and mTOR signaling pathways are required for the effect of Aβ40 on GABAAα6 current and expression in CGNs. A pharmacological blockade of the p75 neurotrophin receptor (p75NTR), but not the insulin or α7‐nAChR receptors, abrogated the effect of Aβ40 on GABAAα6 protein expression and current. Furthermore, the expression of GABAAα6 was lower in CGNs from APP−/− mice than in CGNs from wild‐type mice. Moreover, the internal granule layer (IGL) in APP−/− mice was thinner than the IGL in wild‐type mice. The injection of Aβ40 into the cerebellum reversed this effect, and the application of p75NTR blocking antibody abolished the effects of Aβ40 on cerebellum morphology in APP−/− mice. Our results suggest that low concentrations of Aβ40 play a role in regulating CGN maturation through p75NTR.
DNA sperm damage correlates with nuclear ultrastructural sperm defects in teratozoospermic men

Sperm morphology has consistently been the best indicator of male fertility. Transmission electron microscopy currently provides the most information on the subcellular details of sperm structure. Recently, assessment of sperm DNA damage has been employed to assess fertility potential. The purpose of this work was to link sperm DNA damage, evaluated by an intercalated fluorescent dye, with the structural characteristics of sperm. Conventional semen analysis was performed on samples from men undergoing fertility evaluation. Thirty men were evaluated and assigned to three subgroups based on strict criteria for sperm morphology: normal morphology (>14% normal forms), intermediate morphology (5–14% normal forms), and poor morphology (<5% normal forms). By quantifying acridine orange‐positive cells and ultrastructural sperm defects, we found that the poor morphology pattern group showed a positive association between sperm carrying damaged DNA and the percentage of sperm nucleus with vacuoles (P = 0.01). No statistically significant correlations were established in other ultrastructural characteristics of sperm, including immature chromatin, lytic changes, or abnormal sperm tails. These results suggest that zones without chromatin in the sperm nucleus reflect underlying chromosomal or DNA defects in severe teratozoospermic men. This association should be considered in the evaluation of male fertility.
Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. ASPECTS Study Group. Alberta Stroke Programme Early CT Score.

BACKGROUND Computed tomography (CT) must be done before thrombolytic treatment of hyperacute ischaemic stroke, but the significance of early ischaemic change on CT is unclear. We tested a quantitative CT score, the Alberta Stroke Programme Early CT Score (ASPECTS). METHODS 203 consecutive patients with ischaemic stroke were treated with intravenous alteplase within 3 h of symptom onset in two North American teaching hospitals. All pretreatment CT scans were prospectively scored. The score divides the middle-cerebral-artery territory into ten regions of interest. Primary outcomes were symptomatic intracerebral haemorrhage and 3-month functional outcome. The sensitivity and specificity of ASPECTS for the primary outcomes were calculated. Logistic regression was used to test the association between the score on ASPECTS and the primary outcomes. FINDINGS Ischaemic changes on the baseline CT were seen in 117 (75%) of 156 treated patients with anterior-circulation ischaemia included in the analysis (23 had ischaemia in the posterior circulation and 24 were treated outside the protocol). Baseline ASPECTS value correlated inversely with the severity of stroke on the National Institutes of Health Stroke Scale (r=-0.56, p<0.001). Baseline ASPECTS value predicted functional outcome and symptomatic intracerebral haemorrhage (p<0.001, p=0.012, respectively). The sensitivity of ASPECTS for functional outcome was 0.78 and specificity 0.96; the values for symptomatic intracerebral haemorrhage were 0.90 and 0.62. Agreement between observers for ASPECTS, with knowledge of the affected hemisphere, was good (kappa statistic 0.71-0.89). INTERPRETATION This CT score is simple and reliable and identifies stroke patients unlikely to make an independent recovery despite thrombolytic treatment.
Cdc37 Promotes the Stability of Protein Kinases Cdc28 and Cak1

ABSTRACT In the budding yeast Saccharomyces cerevisiae, Cdc37 is required for the productive formation of Cdc28-cyclin complexes. Thecdc37-1 mutant arrests at Start with low levels of Cdc28 protein, which is predominantly unphosphorylated at Thr169, fails to bind cyclin, and has little protein kinase activity. We show here that Cdc28 and not cyclin is specifically defective in thecdc37-1 mutant and that Cdc37 likely does not act as an assembly factor for Cdc28-cyclin complex formation. We have also found that the levels and activity of the protein kinase Cak1 are significantly reduced in the cdc37-1 mutant. Pulse-chase analysis indicates that Cdc28 and Cak1 proteins are both destabilized when Cdc37 function is absent during but not after translation. In addition, Cdc37 promotes the production of Cak1, but not that of Cdc28, when coexpressed in insect cells. We conclude that budding yeast Cdc37, like its higher eukaryotic homologs, promotes the physical integrity of multiple protein kinases, perhaps by virtue of a cotranslational role in protein folding.
NF‐κB signalling proteins p50/p105, p52/p100, RelA, and IKKϵ are over‐expressed in oesophageal squamous cell carcinomas

Aims: Nuclear factor‐kappa B (NF‐κB) activation has been recognised as an important mechanism in the development of cancers. However, expression status of NF‐κB‐related proteins in oesophageal squamous cell carcinoma (ESCC) tissues is largely unknown. In this study, we analysed expressions of NF‐κB members (p50/105, p52/p100 and RelA) and IKKε in ESCC tissues. Methods: We analysed the expression of p50/105, p52/p100, RelA and IKKε in 58 ESCC patients' tissues by immunohistochemistry using a tissue microarray (TMA) method. Results: Normal oesophageal squamous cells expressed p50/105, p52/p100 and RelA in 5%, 79% and 10% of the tissues in cytoplasm, respectively; however, only p52/p100 was expressed in the nuclei (12%). The cancer tissues expressed p50/105, p52/p100 and RelA in 93%, 95% and 95% in cytoplasm and/or nuclei, respectively. Nuclear immunostainings of NF‐κB members p50/105, p52/p100 and RelA, which are considered activation of NF‐κB signalling, were observed in 34%, 60% and 26% of the cancers, respectively. IKKε is expressed in cytoplasm in 50% of the normal squamous tissues and 84% of the cancer tissues. However, none of the expression of p50/105, p52/p100, RelA or IKKε was associated with pathological characteristics, including differentiation, depth of invasion and TNM stage. Conclusion: The increased nuclear expressions of p50/105, p52/p100 and RelA as well as increased cytoplasmic expression of IKKε in the ESCC tissues compared to the normal squamous cells suggested that over‐expression of these proteins may be related to activation of the NF‐κB pathway and might play a role in the development of ESCC.
Effect of preoperative biliary drainage on surgical results after pancreaticoduodenectomy in patients with distal common bile duct cancer: focused on the rate of decrease in serum bilirubin.

AIM To examine if the rate of decrease in serum bilirubin after preoperative biliary drainagecan be used as a predicting factor for surgical complications and postoperative recovery after pancreaticoduodenectomy in patients with distal common bile duct cancer. METHODS A retrospective study was performed in 49 consecutive patients who underwent pancreaticoduodenectomy for distal common bile duct cancer. Potential risk factors were compared between the complicated and uncomplicated groups. Also, the rates of decrease in serum bilirubin were compared pre- and postoperatively. RESULTS Preoperative biliary drainage (PBD) was performed in 40 patients (81.6%). Postoperative morbidity and mortality rates were 46.9% (23/49) and 6.1% (3/49), respectively. The presence or absence of PBD was not different between the complicated and uncomplicated groups. In patients with PBD, neither the absolute level nor the rate of decrease in serum bilirubin was significantly different. Patients with rapid decrease preoperatively showed faster decrease during the first postoperative week (5.5 +/- 4.4 micromol/L vs -1.7 +/- 9.9 micromol/L, P = 0.004). CONCLUSION PBD does not affect the surgical outcome of pancreaticoduodenectomy in patients with distal common bile duct cancer. There is a certain group of patients with a compromised hepatic excretory function, which is represented by the slow rate of decrease in serum bilirubin after PBD.
Regulation and its reform

Introduction PART 1: A Theory of Regulation 1. Typical Justifications for Regulation 2. Cost-of-Service Ratemaking 3. Historically Based Price Regulation 4. Allocation under a Public Interest Standard 5. Standard Setting 6. Historically Based Allocation 7. Individualized Screening 8. Alternatives to Classical Regulation 9. General Guidelines for Policy Makers PART 2: Appropriate Solutions 10. Match and Mismatch 11. Mismatch: Excessive Competition and Airline Regulation 12. Mismatch: Excessive Competition and the Trucking Industry 13. Mismatch: Rent Control and Natural Gas Field Prices 14. Partial Mismatch: Spillovers and Environmental Pollution 15. Problems of a Possible Match: Natural Monopoly and Telecommunications PART 3: Practical Reform 16. From Candidate to Reform 17. Generic Approaches to Regulatory Reform Appendix 1: The Regulatory Agencies Appendix 2: A Note on Administrative Law Further Reading Notes Index
Antiproliferative Effects of Local Anesthetics on Mesenchymal Stem Cells: Potential Implications for Tumor Spreading and Wound Healing

Background: Mesenchymal stem cells (MSC) are self-renewing clonal progenitor cells of nonhematopoietic tissues that exhibit a marked tropism to wounds and tumors. The authors' studies aimed at exploring how local anesthetics would affect MSC biology. Methods: Proliferation, colony formation, in vitro wound healing, and bone differentiation assays of culture-expanded bone-marrow-derived murine MSC were performed in the presence of increasing concentrations of lidocaine, ropivacaine, and bupivacaine. Cytotoxicity was monitored by measuring lactate dehydrogenase activity and phosphatidylserine exposure/propidium iodide staining (early apoptotic cells/necrotic cells). Measurements of mitochondrial function in intact and permeabilized cells, transcriptional changes, and changes in nuclear factor &kgr;-light-chain-enhancer of activated B cells signaling in MSC treated with ropivacaine were used to further characterize the biologic effects of local anesthetics on MSC. Results: All local anesthetics reduced MSC proliferation at 100 &mgr;M, consistent with cell cycle delay or arrest at the G0/1-S phase transition. They increased lactate dehydrogenase release and the number of annexin V-positive MSC but not necrotic MSC. Colony formation was decreased, differentiation into osteoblasts impaired, and in vitro wound healing delayed. Mitochondrial respiration and adenosine 5′-triphosphate concentrations were reduced. Microarray analysis revealed significant expression changes in lysosomal genes and genes controlling sterol metabolism, indicating an impaired phospholipid metabolism in the lysosome. Multiple transcriptional programs related to cell differentiation, tumorigenesis, and metastasis were negatively affected by ropivacaine. Conclusions: The authors' studies demonstrate that local anesthetics significantly affect important aspects of MSC biology. These experiments provide novel rationales for the perioperative use of local anesthetics in patients with cancer but also highlight the potentially detrimental effects of local anesthetics on wound healing.
Evidence‐based medicine in plastic surgery: where did it come from and where is it going?

Evidence‐based medicine, particularly randomized controlled trials, influence many of the daily decisions within plastic surgery as well as nearly every other medical specialty, and will continue to play a larger role in medicine in the future. Even though it is certainly not a new idea, evidence‐based medicine continues to remain a hot topic among members of the healthcare community. As evidence‐based medicine continues to grow and evolve, it is becoming more important for all physicians to understand the fundamentals of evidence‐based medicine: how evidence‐based medicine has changed, and how to successfully incorporate it into the daily practice of medicine.
Cloning, Expression, and Catalytic Activity ofHelicobacter hepaticus Urease

ABSTRACT Helicobacter hepaticus causes disease in the liver and lower intestinal tract of mice. It is strongly urease positive, although it does not live in an acidic environment. The H. hepaticus urease gene cluster was expressed in Escherichia coli with and without coexpression of the Helicobacter pylori nickel transporter NixA. As for H. pylori, it was difficult to obtain enzymatic activity from recombinant H. hepaticus urease; special conditions including NiCl2supplementation were required. The H. hepaticus urease cluster contains a homolog of each gene in the H. pyloriurease cluster, including the urea transporter gene ureI. Downstream genes were homologs of the nik nickel transport operon of E. coli. Nongastric H. hepaticusproduces urease similar to that of H. pylori.
Organizations, populations, and fields: Investigating organizational heterogeneity through a multilevel case study design

In this chapter, we describe a multilevel, longitudinal, comparative case study approach for investigating organizational heterogeneity based on our experience studying institutional change in the health care field (Scott, Ruef, Mendel, & Caronna, 2000). By examining the relationship between organizations, populations, and fields, differences between organizations can be captured in terms of their organizational identities as well as their (changing) relationships with the organizational field. We discuss the analytical strategies we used in our study of institutional change and describe our findings of organizational heterogeneity across levels and over time. We conclude with suggestions for future research that incorporate elements of our study design and lessons from our research process and outcomes.
Changing Trends in Health Care Tourism

Despite much coverage in the popular press, only anecdotal evidence is available on medical tourists. At first sight, they seemed confined to small and narrowly defined consumer segments: individuals seeking bargains in cosmetic surgery or uninsured and financially distressed individuals in desperate need of medical care. The study reported in this article is the first empirical investigation of the medical tourism consumer market. It provides the demographic profile, motivations, and value perceptions of health care consumers who traveled abroad specifically to receive medical care. The findings suggest a much broader market of educated and savvy health care consumers than previously thought. In the backdrop of the health care reform, the article concludes with implications for health care providers.
Saliency prediction with scene structural guidance

Previous works have suggested the role of scene information in directing gaze. The structure of a scene provides global contextual information that complements local object information in saliency prediction. In this study, we explore how scene envelopes such as openness, depth, and perspective affect visual attention in natural outdoor images. To facilitate this study, an eye tracking dataset is first built with 500 natural scene images and eye tracking data with 15 subjects free-viewing the images. We make observations on scene layout properties and propose a set of scene structural features relating to visual attention. We further integrate features from deep neural networks and use the set of complementary features for saliency prediction. Our features are independent of and can work together with many computational modules, and this work demonstrates the use of Multiple kernel learning (MKL) as an example to integrate the features at low- and high-levels. Experimental results demonstrate that our model outperforms existing methods and our scene structural features can improve the performance of other saliency models in outdoor scenes.
The Citrobacter rodentium Genome Sequence Reveals Convergent Evolution with Human Pathogenic Escherichia coli

ABSTRACT Citrobacter rodentium (formally C itrobacter freundii biotype 4280) is a highly infectious pathogen that causes colitis and transmissible colonic hyperplasia in mice. In common with enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively), C. rodentium exploits a type III secretion system (T3SS) to induce attaching and effacing (A/E) lesions that are essential for virulence. Here, we report the fully annotated genome sequence of the 5.3-Mb chromosome and four plasmids harbored by C. rodentium strain ICC168. The genome sequence revealed key information about the phylogeny of C. rodentium and identified 1,585 C. rodentium-specific (without orthologues in EPEC or EHEC) coding sequences, 10 prophage-like regions, and 17 genomic islands, including the locus for enterocyte effacement (LEE) region, which encodes a T3SS and effector proteins. Among the 29 T3SS effectors found in C. rodentium are all 22 of the core effectors of EPEC strain E2348/69. In addition, we identified a novel C. rodentium effector, named EspS. C. rodentium harbors two type VI secretion systems (T6SS) (CTS1 and CTS2), while EHEC contains only one T6SS (EHS). Our analysis suggests that C. rodentium and EPEC/EHEC have converged on a common host infection strategy through access to a common pool of mobile DNA and that C. rodentium has lost gene functions associated with a previous pathogenic niche.
Memory-augmented Neural Machine Translation

Neural machine translation (NMT) has achieved notable success in recent times, however it is also widely recognized that this approach has limitations with handling infrequent words and word pairs. This paper presents a novel memory-augmented NMT (M-NMT) architecture, which stores knowledge about how words (usually infrequently encountered ones) should be translated in a memory and then utilizes them to assist the neural model. We use this memory mechanism to combine the knowledge learned from a conventional statistical machine translation system and the rules learned by an NMT system, and also propose a solution for out-of-vocabulary (OOV) words based on this framework. Our experiments on two Chinese-English translation tasks demonstrated that the M-NMT architecture outperformed the NMT baseline by 9.0 and 2.7 BLEU points on the two tasks, respectively. Additionally, we found this architecture resulted in a much more effective OOV treatment compared to competitive methods.
Long-term effects of foetal undernutrition on intermediary metabolism in growing lambs

The objective of this study was to investigate the effects of foetal undernutrition on the metabolism in growing lambs. Seven-month-old lambs whose mothers had been fed either restrictively (RN; n = 14) or adequately (AN; n = 6) in late gestation were fasted for three days. One hour before fasting and after 48 h and 72 h fasting, changes in plasma concentrations of metabolites, i.e. glucose, non-esterified fatty acids (NEFA), 3-β-hydroxybutyrate (BOHB) and urea as well as hormones, i.e. insulin, the insulin-like growth factor (IGF-I) and leptin, were determined. Blood glucose, NEFA, urea, insulin, IGF-I and leptin were not different between the two groups of lambs. Unexpectedly, at the end of the 3 d fasting, in spite of lower NEFA concentration (1.6 ± 0.03 vs. 1.9 ± 0.05 mM in Groups RN and AN, respectively), the BOHB concentration in RN lambs (0.94 ± 0.02 mM) was significantly higher than that in AN lambs (0.78 ± 0.04 mM). This higher rate of BOHB production might be interpreted as perturbations in ketone body metabolism potentially induced by undernutrition during foetal life. However, more investigations are necessary to clarify this interrelationship.
Rigor in Qualitative research: Promoting quality in Social Science Research

Internationally, there is an increasing call for in-depth and rigorous research to enhance the evidence-based practice of most of the practice professions. This article is reviewing various published articles on rigor of qualitative research and discusses on the various criteria presented in these articles to ensure credibility, transferability, dependability, and conformability. For the purpose of this analysis, the author has selected five published articles those analyses rigor in qualitative research. Majority of these articles based their rigor criteria in the suggestions provided by Lincoln and Guba. In-depth analysis also shows that authors tried to develop further new parameters ensure the credibility of qualitative researches. Finally, the author is summarizing the major suggestions provided in these articles to ensure the rigor of qualitative research studies.