Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of lactate with a hadamard slice selected, selective multiple quantum coherence, chemical shift imaging sequence (HDMD‐SelMQC‐CSI) on a clinical MRI scanner: Application to tumors and muscle ischemia

Lactate is an important metabolite in normal and malignant tissues detectable by NMR spectroscopy; however, it has been difficult to clinically detect the lactate methyl resonance because it is obscured by lipid resonances. The selective homonuclear multiple quantum coherence transfer technique offers a method for distinguishing lipid and lactate resonances. We implemented a three‐dimensional selective homonuclear multiple quantum coherence transfer version with Hadamard slice selection and two‐dimensional phase encoding (Hadamard encoded–selective homonuclear multiple quantum coherence transfer–chemical shift imaging) on a conventional clinical MR scanner. Hadamard slice selection is explained and demonstrated in vivo. This is followed by 1‐cm3 resolution lactate imaging with detection to 5‐mM concentration in 20 min on a 3‐T clinical scanner. An analysis of QSel gradient duration and amplitude effects on lactate and lipid signal is presented. To demonstrate clinical feasibility, a 5‐min lactate scan of a patient with a non‐Hodgkin's lymphoma in the superficial thigh is reported. The elevated lactate signal coincides with the T2‐weighted image of this tumor. As a test of selective homonuclear multiple quantum coherence transfer sensitivity, a thigh tourniquet was applied to a normal volunteer and an increase in lactate was detected immediately after tourniquet flow constriction. In conclusion, the Hadamard encoded–selective homonuclear multiple quantum coherence transfer–chemical shift imaging sequence is demonstrated on a phantom and in two lipid‐rich, clinically relevant, in vivo conditions. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Resistance to glycopeptides in enterococci.

The development of resistance to glycopeptides (vancomycin and teicoplanin) is one of the best examples of the alternation between success and failure that spans the history of the antibiotic era. The introduction of penicillin G was revolutionary. However, the emergence in the 1950s of clinical isolates of Staphylococcus aureus that were resistant to penicillins and subsequently to erythromycin and tetracyclines stimulated the development of large-scale screening programs for new drugs. Under these circumstances, an American missionary, Reverend W. M. Bouw, provided Eli Lilly (Indianapolis) with a soil sample from Borneo [1]. The organism that produces vancomycin, Amycolatopsis orientalis, was isolated from this sample in 1954. Since vancomycin proved to be potent against grampositive bacteria, including penicillinase-producing staphylococci, it was licensed for human use in record time. However, the renal toxicity and ototoxicity associated with vancomycin therapy (due for the most part to impurities in the drug) together with the introduction of new penicillinase-resistant /-lactams led to a rapid decline in the use of vancomycin. In the 1980s, interest in vancomycin revived because of several factors. During this period, methicillin-resistant and multiresistant staphylococci, against which vancomycin is often the only active antibiotic, were emerging worldwide. At the same time, medical advances had resulted in the prolongation of life for increasingly fragile, immunocompromised patients who are exposed to opportunistic pathogens such as multiresistant gram-positive organisms. In addition, it was determined that pseudomembranous colitis could be treated with oral vancomycin, and a new glycopeptide, teicoplanin, was introduced in 1984 in certain European countries. The apparent absence of resistance to vancomycin in grampositive bacteria and a decrease in the toxicity associated with vancomycin therapy (purified formulations of the drug had become available) led to a notable increase in the prescription of this antibiotic. In the United States, a 20-fold increase in the consumption of vancomycin was observed over a 10-year period at a university hospital [2].
On random walk based graph sampling

Random walk based graph sampling has been recognized as a fundamental technique to collect uniform node samples from a large graph. In this paper, we first present a comprehensive analysis of the drawbacks of three widely-used random walk based graph sampling algorithms, called re-weighted random walk (RW) algorithm, Metropolis-Hastings random walk (MH) algorithm and maximum-degree random walk (MD) algorithm. Then, to address the limitations of these algorithms, we propose two general random walk based algorithms, named rejection-controlled Metropolis-Hastings (RCMH) algorithm and generalized maximum-degree random walk (GMD) algorithm. We show that RCMH balances the tradeoff between the limitations of RW and MH, and GMD balances the tradeoff between the drawbacks of RW and MD. To further improve the performance of our algorithms, we integrate the so-called delayed acceptance technique and the non-backtracking random walk technique into RCMH and GMD respectively. We conduct extensive experiments over four real-world datasets, and the results demonstrate the effectiveness of the proposed algorithms.
Incidence and risk factors of hypotension and bradycardia after spinal anesthesia for cesarean section.

BACKGROUND Hypotension or bradycardia after spinal anesthesia for cesarean section remain common and are serious complications. The current study evaluated factors associated to the incidences of hypotension or bradycardia in this context. MATERIAL AND METHOD A prospective cross sectional study from November 1, 2004 to July 31, 2005 was conducted on 722 parturients undergoing cesarean section under spinal anesthesia. T-test and Chi-square test were used in univariate analysis to compare continuous data and categorical data respectively. Multivariate logistic regression was performed on the variables hypotension (systolic pressure decrease > 30% of baseline value) and bradycardia (heart rate < 60 bpm) p-value < 0.05 was considered significant. RESULTS Incidence of hypotension and bradycardia were 52.6% and 2.5%. The probability of hypotension increased with estimated blood loss 500-1000 mL (odds ratio [OR] = 1.86; 95% CI 1.30-2.67, p = 0.001), estimated blood loss > 1000 mL (OR = 5.31; 95% CI 1.47-19.19, p = 0.011), and analgesia level > T4 (OR = 1.94; 95% CI 1.18-3.19, p = 0.009). Hypotension occurred despite left uterine displacement (OR = 1.56; 95% CI 1.11-2.19, p = 0.01). Risk factors associated with bradycardia were adding intrathecal morphine 0.2 mg (0.2 mL) (OR = 4.61; 95% CI 1.31-16.19, p = 0.017) to local anesthetics. CONCLUSION The present results indicated that the incidence of hypotension after spinal anesthesia for cesarean section increased with amount of estimated blood loss > 500 mL and analgesic level > T4. Adding intrathecal morphine 0.2 mg (0.2 mL) to local anesthetics increased incidence of bradycardia.
Dexmedetomidine and clonidine in epidural anaesthesia: A comparative evaluation

Efforts to find a better adjuvant in regional anaesthesia are underway since long. Aims and objectives are to compare the efficacy and clinical profile of two α-2 adrenergic agonists, dexmedetomidine and clonidine, in epidural anaesthesia with special emphasis on their sedative properties and an ability to provide smooth intra-operative and post-operative analgesia. A prospective randomized study was carried out which included 50 adult female patients between the ages of 44 and 65 years of (American Society of Anaesthesiologists) ASAI/II grade who underwent vaginal hysterectomies. The patients were randomly allocated into two groups; ropivacaine + dexmedetomidine (RD) and ropivacaine + clonidine (RC), comprising of 25 patients each. Group RD was administered 17 ml of 0.75% epidural ropivacaine and 1.5 μg/kg of dexmedetomidine, while group RC received admixture of 17 ml of 0.75% ropivacaine and 2 μg/kg of clonidine. Onset of analgesia, sensory and motor block levels, sedation, duration of analgesia and side effects were observed. The data obtained was subjected to statistical computation with analysis of variance and chi-square test using statistical package for social science (SPSS) version 10.0 for windows and value of P < 0.05 was considered significant and P < 0.0001 as highly significant. The demographic profile, initial and post-operative block characteristics and cardio-respiratory parameters were comparable and statistically non-significant in both the groups. However, sedation scores with dexmedetomidine were better than clonidine and turned out to be statistically significant (P < 0.05). The side effect profile was also comparable with a little higher incidence of nausea and dry mouth in both the groups which was again a non-significant entity (P > 0.05). Dexmedetomidine is a better neuraxial adjuvant compared to clonidine for providing early onset of sensory analgesia, adequate sedation and a prolonged post-operative analgesia.
Numerical analysis of thermo-mechanical phenomena of hardening process of elements made of carbon steel C80U

The work concerns numerical analysis of thermal phenomena, phase transformations and mechanical phenomena associated with hardening of carbon steel C80U. The following transformations were assumed: initial structure – austenite, austenite – perlite, bainite and austenite – martensite. Numerical algorithms for evaluation of fractions of phases and their kinetics based on continuous heating and cooling diagrams (CCT) were worked out. In the algorithm of thermal phenomena relation of thermophysical values to temperature and source of phase transformations were taken into account. The dilatometric tests on the simulator of thermal cycles were performed, during which the hardening of the elements made of carbon steel C80U was simulated. The results of dilatometric tests were compared with the results of the test numerical simulations. In this way the derived models for evaluating phase content and kinetics of transformations in heating and cooling processes were verified. The stresses generated during hardening were assumed to result from thermal load, structural plastic deformations and transformation plasticity. The hardened material was assumed to be elastic-plastic, and in order to mark plastic strains the non-isothermal plastic law of flow with the isotropic strengthening and condition plasticity of Huber-Misses were used. Thermophysical properties present in the model of mechanical phenomena were made dependant on both the phase composition and on temperatures. The results of numerical simulations confirm correctness of the algorithms that were worked out.
Metabolic Syndrome in Inflammatory Bowel Disease: A Real Relationship or Just a Coincidence

Background and aim: Presence of metabolic syndrome along with inflammatory diseases is being reported with increased frequency. The aim of this study was to investigate the presence of metabolic syndrome in inflammatory bowel disease patients. Materials and methods: Fifty-one patients with ulcerative colitis, 34 patients with Crohn’s disease and 88 healthy controls were included in this study. All of the patients were in remission state. Subjects were classified as having the metabolic syndrome based on the National Cholesterol Education Program (NCEP) and the modified World Health Organization (WHO) definition. Results: The prevalence of metabolic syndrome in patients with ulcerative colitis was 16% according to the NCEP and 23.5% according to the WHO, and that in patients with Crohn’s disease was 8.8% according to the NCEP and 14.7% according to the WHO. The prevalence of metabolic syndrome in control group was 18% according to the NCEP and 15.7% according to the WHO. When inflammatory bowel disease patients and control groups were compared with respect to the presence of metabolic syndrome, there was no statistically significant difference between the two groups according to neither NCEP nor WHO. Conclusion: Although it is predicted that metabolic syndrome develops lesser since inflammatory bowel disease patients as they are considered to have lower body mass index, frequency of metabolic syndrome is not less than control group according to the results of our study. Therefore, possibility of metabolic syndrome in inflammatory bowel disease patients should not be overlooked and it should be considered that it can be used in patient follow-up. Abbreviations: IBD: Inflammatory bowel disease; CD: Crohn’s disease; UC: Ulcerative colitis; TNF: Tumor necrosis factor; RA: Rheumatoid arthritis; SLE: Systemic lupus erythematosus; CDAI: Crohn disease activity Index; BMI: Body mass index; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; IR: Insulin resistance; EGIR: European group for the study of insulin Resistance; NCEP: National cholesterol education program; ACE: American college of cardiology; IDF: International diabetes federation.
Clinical and biochemical differences in patients having Parkinson disease with vs without GBA mutations.

IMPORTANCE Biochemical abnormalities present in GBA (mut/wt) carriers may offer new pathogenetic insights to and potential therapeutic targets in Parkinson disease (PD). OBJECTIVE To determine whether patients having PD with vs without GBA mutations differ in clinical phenotype or plasma protein expression. DESIGN AND SETTING Case-control study of patients having PD with vs without GBA mutations. Clinical characteristics were compared between groups, and biochemical profiling of 40 plasma proteins was performed to identify proteins that differed in expression between groups. PARTICIPANTS The discovery cohort included 20 patients having PD with GBA mutations. Clinical characteristics of GBA-associated PD cases were compared with those of 242 patients having PD in whom GBA mutations were excluded by full gene sequencing. MAIN OUTCOME MEASURES Biochemical profiling was available for all 20 GBA-associated PD cases, as well as a subset (87 of 242) of the GBA-negative PD cases. The replication cohort included 19 patients having PD with GBA mutations and 41 patients having PD without GBA mutations. RESULTS Compared with patients having PD without GBA mutations, patients having PD with GBA mutations were younger at disease onset (P = .04) and were more likely to demonstrate cognitive dysfunction (P = .001). In a multiple regression model that included age, sex, and assay batch as covariates, GBA mutation status was significantly associated with plasma levels of interleukin 8 (P = .001), monocyte chemotactic protein 1 (P = .008), and macrophage inflammatory protein 1α (P = .005). The association between interleukin 8 and GBA mutation status was replicated (P = .03) in a separate cohort of patients having PD with vs without GBA mutations. CONCLUSIONS AND RELEVANCE Patients having PD with GBA mutations have earlier age at disease onset and are more likely to demonstrate cognitive dysfunction. Monocyte-associated inflammatory mediators may be elevated in patients having PD with GBA mutations.
Come in and take your coat off – how host cells provide endocytosis for virus entry

Viruses are intracellular parasites that rely upon the host cell machinery for their life cycle. Newly generated virus particles have to transmit their genomic information to uninfected cells/organisms. Viral entry is the process to gain access to viral replication sites within uninfected cells, a multistep course of events that starts with binding to target cells. Since viruses are simple in structure and composition and lack any locomotive capacity, viruses depend on hundreds of host cell proteins during entry. Most animal viruses take advantage of endocytosis to enter cells. Cell biological, morphological and biochemical studies, live cell imaging and systematic approaches have identified various new endocytic mechanisms besides clathrin‐mediated endocytosis, macropinocytosis and caveolar/lipid raft‐mediated endocytosis. Hence, studying virus entry has become ever more complex. This review provides a cell biological overview of the existing endocytic mechanisms and strategies used or potentially used by viruses to enter cells.
Q-learning for Optimal Control of Continuous-time Systems

In this paper, two Q-learning (QL) methods are proposed and their convergence theories are established for addressing the model-free optimal control problem of general nonlinear continuous-time systems. By introducing the Q-function for continuous-time systems, policy iteration based QL (PIQL) and value iteration based QL (VIQL) algorithms are proposed for learning the optimal control policy from real system data rather than using mathematical system model. It is proved that both PIQL and VIQL methods generate a nonincreasing Q-function sequence, which converges to the optimal Q-function. For implementation of the QL algorithms, the method of weighted residuals is applied to derived the parameters update rule. The developed PIQL and VIQL algorithms are essentially off-policy reinforcement learning approachs, where the system data can be collected arbitrary and thus the exploration ability is increased. With the data collected from the real system, the QL methods learn the optimal control policy offline, and then the convergent control policy will be employed to real system. The effectiveness of the developed QL algorithms are verified through computer simulation.
Antitumor effect of pyrrolo-1,5-benzoxazepine-15 and its synergistic effect with Oxaliplatin and 5-FU in colorectal cancer cells

ABSTRACT Some compounds of a series of novel pyrrolo-1,5-benzoxa(thia)zepine, a well-known group of tubulin targeting agents, display anti-tumor effects mainly inducing cell cycle arrest and apoptosis in several human cancer models. A member of this family, pyrrolo-1,5-benzoxazepine-15 (PBOX-15), has previously shown potent pro-apoptotic activity in a variety of human tumor cell types, with minimal toxicity toward normal blood and bone marrow cells. In this study, we evaluated the PBOX-15-mediated effects in human colorectal cancer cell (CRC) lines, DLD-1 and HT-29. The compound, used at concentrations equal to or greater than 1 μM, inhibited the proliferation of human CRC cells, inducing a significant cell cycle arrest in the G2/M phase. In DLD-1 cells, treatments prolonged over 48 h triggered a strong activation of the intrinsic apoptotic pathway as indicated by activation of caspase-9, caspase-3 and PARP cleavage. Moreover, nanomolar concentrations of PBOX-15, significantly improved the oxaliplatin and 5-fluouracil-induced anti-proliferative effects in DLD1 cell line. The observed synergistic interaction of both PBOX-15/Oxaliplatin and PBOX-15/5FU may involve activation of p38 MAPK and JNK pathway, which in turn significantly increased caspase-3 cleavage in DLD-1 cells, treated with PBOX-5/Oxaliplatin but not with PBOX-15/5FU. Moreover, PBOX-15/5FU-treated cells showed an increase in expression of the pro-apoptotic protein Bax. Taken together, these results show that PBOX-15 could represent a promising compound for the treatment of human CRC and a strong candidate for novel therapeutic options.
Cell-free DNA as a diagnostic marker for cancer: current insights

The increasing knowledge of the molecular pathogenesis of cancer and the rapid development of new molecular techniques are promoting the study of early molecular alterations involved in cancer development in body fluids. Specific genetic and epigenetic alterations could be found in plasma, serum, and urine cell-free DNA (cfDNA) and could potentially be used as diagnostic biomarkers for several types of cancers. This review focuses on the role of cfDNA in diagnosis: a PubMed search was performed by selecting papers according to journal impact factor and robustness of statistical analysis. A comprehensive evaluation of “liquid biopsy”, including cfDNA analysis, will be one of the critical challenges to better understand the early mechanisms of cancer development.
Unshelled abalone and corrupted urchins: development of marine calcifiers in a changing ocean

The most fragile skeletons produced by benthic marine calcifiers are those that larvae and juveniles make to support their bodies. Ocean warming, acidification, decreased carbonate saturation and their interactive effects are likely to impair skeletogenesis. Failure to produce skeleton in a changing ocean has negative implications for a diversity of marine species. We examined the interactive effects of warming and acidification on an abalone (Haliotis coccoradiata) and a sea urchin (Heliocidaris erythrogramma) reared from fertilization in temperature and pH/pCO2 treatments in a climatically and regionally relevant setting. Exposure of ectodermal (abalone) and mesodermal (echinoid) calcifying systems to warming (+2°C to 4°C) and acidification (pH 7.6–7.8) resulted in unshelled larvae and abnormal juveniles. Haliotis development was most sensitive with no interaction between stressors. For Heliocidaris, the percentage of normal juveniles decreased in response to both stressors, although a +2°C warming diminished the negative effect of low pH. The number of spines produced decreased with increasing acidification/pCO2, and the interactive effect between stressors indicated that a +2°C warming reduced the negative effects of low pH. At +4°C, the developmental thermal tolerance was breached. Our results show that projected near-future climate change will have deleterious effects on development with differences in vulnerability in the two species.
Criteria for Annotation of Plant MicroRNAs

MicroRNAs (miRNAs) are ∼21 nucleotide noncoding RNAs produced by Dicer-catalyzed excision from stem-loop precursors. Many plant miRNAs play critical roles in development, nutrient homeostasis, abiotic stress responses, and pathogen responses via interactions with specific target mRNAs. miRNAs are not the only Dicer-derived small RNAs produced by plants: A substantial amount of the total small RNA abundance and an overwhelming amount of small RNA sequence diversity is contributed by distinct classes of 21- to 24-nucleotide short interfering RNAs. This fact, coupled with the rapidly increasing rate of plant small RNA discovery, demands an increased rigor in miRNA annotations. Herein, we update the specific criteria required for the annotation of plant miRNAs, including experimental and computational data, as well as refinements to standard nomenclature.
Optimizing Bone Health and Calcium Intakes of Infants, Children, and Adolescents

Most older children and adolescents in the United States currently do not achieve the recommended intake of calcium. Maintaining adequate calcium intake during childhood and adolescence is necessary for the development of peak bone mass, which may be important in reducing the risk of fractures and osteoporosis later in life. Optimal calcium intake is especially relevant during adolescence, when most bone mineral accretion occurs. Because of the influence of the family's diet on the diet of children and adolescents, adequate calcium intake by all members of the family is important. Assessment of calcium intake can be performed in the physician's office. A well-rounded diet including low-fat dairy products, fruits, and vegetables and appropriate physical activity are important for achieving good bone health. Establishing these practices in childhood is important so that they will be followed throughout the life span.