Miracle-dz/UniFAR-FTUs huggingface dataset:
Prophylactic octreotide for pancreatoduodenectomy: more harm than good?

BACKGROUND Most accrued evidence regarding prophylactic octreotide for a pancreatoduodenectomy (PD) predates the advent of the International Study Group of Pancreatic Fistula (ISGPF) classification system for a post-operative pancreatic fistula (POPF), and its efficacy in the setting of high POPF risk is unknown. The Fistula Risk Score (FRS) predicts the risk and impact of a clinically relevant (CR)-POPF and can be useful in assessing the impact of octreotide in scenarios of risk. METHODS From 2001-2013, 1018 PDs were performed at four institutions, with octreotide administered at the surgeon's discretion. The FRS was used to analyse the occurrence and burden of POPF across various risk scenarios. RESULTS Overall, 391 patients (38.4%) received octreotide. A CR-POPF occurred more often when octreotide was used (21.0% versus 7.0%; P < 0.001), especially when there was advanced FRS risk. Octreotide administration also correlated with an increased hospital stay (mean: 13 versus 11 days; P < 0.001). Regression analysis, controlling for FRS risk, demonstrated that octreotide increases the risk for CR-POPF development. CONCLUSION This multi-institutional study, using ISGPF criteria, evaluates POPF development across the entire risk spectrum. Octreotide appears to confer no benefit in preventing a CR-POPF, and may even potentiate CR-POPF development in the presence of risk factors. This analysis suggests octreotide should not be utilized as a POPF mitigation strategy.
Molecular Interactions of MMP-13 C-Terminal Domain with Chondrocyte Proteins

Matrix metalloproteinases (MMP)-13 activity is necessary for normal skeletal development and plays a central role in cartilage degeneration associated with osteoarthritis (OA). The studies we described here examine the interactions of the hemopexin domain of MMP-13 with proteins secreted by human chondrocytes in culture. The hemopexin domain of the MMPs and many other proteins in which this structure is found mediates protein function by forming the primary site of interaction with other proteins. We have modified a tandem affinity expression tag (hTAP) to enable efficient expression of the tagged bait protein. In this case the MMP-13 C-terminal domain (CTD) comprises hinge and hemopexin domain, and we immobilized the fusion construct on a column of agarose bound immunoglobin G. The MMP-13 CTD affinity column so generated enabled the efficient and gentle isolation of interacting proteins from the culture medium of human articular chondrocytes. TIMP1 and α2-macroglobulin previously shown to interact with MMP-13 as well as several proteins, fibronectin, type VI collagen and xylosyltransferase 1 and several proteoglycans, decorin, syndecan 4 and serglycin not previously recognized as interacting with MMP-13 were identified by mass spectrometry. The interaction between isolated proteins and MMP-13 CTD was verified by yeast two hybrid analysis. We also demonstrated serglycin expression by chondrocytes for the first time and its co localization with MMP-13 in a cytoplasmic granular morphology. The consequence of these interactions remains to be demonstrated, however; binding to MMP-13 suggests a role in the regulation of cartilage degradation.
MDAN-21: A Bivalent Opioid Ligand Containing mu-Agonist and Delta-Antagonist Pharmacophores and Its Effects in Rhesus Monkeys

MDAN-21, 7′-{2-[(7-{2-[({(5α, 6α)-4,5-Epoxy-3,14-dihydroxy-17-methylmorphin-6-yl}-aminocarbonyl)metoxy]-acetylamino}-heptylaminocarbonyl)-methoxy]-acetylamino}-naltrindole, a bivalent opioid ligand containing a mu-opioid receptor agonist (derived from oxymorphone) linked to the delta-opioid receptor antagonist (related to naltrindole) by a spacer of 21 atoms, was reported to have potent analgesic properties in mice. Tolerance, physical dependence, and conditioned place preference were not evident in that species. The finding that bivalent ligands in this series, with spacers 19 atoms or greater, were devoid of tolerance and dependence led to the proposal that MDAN-21 targets heteromeric mu-delta-opioid receptors. The present study focused on its effects in nonhuman primates (Macaca mulatta), a species with a physiology and behavioral repertoire not unlike humans. With regard to opioids, this species usually better predicts clinical outcomes. MDAN-21 substituted for morphine in morphine-dependent monkeys in the remarkably low dose range 0.006–0.032 mg/kg, subcutaneously. Although MDAN-21 failed to produce reliable thermal analgesia in the dose range 0.0032–0.032 mg/kg, intramuscularly, it was active in the same dose range and by the same route of administration, in the capsaicin-induced thermal allodynia assay. The results suggest that MDAN-21 may be useful in the treatment of opioid dependence and allodynia. The data provide additional evidence that opioid withdrawal is associated with sensitized pain.
Fibrinolysis for intermediate-risk pulmonary embolism.

To the Editor: In the Pulmonary Embolism Thrombolysis (PEITHO) study (April 10 issue),1 a bolus of unfractionated heparin was withheld from 303 patients because they had just received subcutaneous low-molecular-weight heparin or fondaparinux. Low-molecular-weight heparin in particular has a slow onset of action, taking 4 to 6 hours to reach full effect.2 This delay in the effect of treatment may have been unfavorable to patients not receiving tenecteplase, among whom the incidence of hemodynamic decompensation (often within the first day after randomization) was higher than that among patients receiving tenecteplase. Guidelines support the safety of low-molecularweight heparin in patients with pulmonary embolism. Caution is warranted, however, because the majority of relevant trials (10 of 12 trials in a key meta-analysis3) used low-molecular-weight heparin after an initial bolus of unfractionated heparin. Omitting this bolus may be unsafe, particularly in high-risk patients such as those involved in the PEITHO study. Previous guidelines have recommended a bolus of unfractionated heparin before the administration of lowmolecular-weight heparin.4 Later, for some reason, this recommendation disappeared. We would like to know outcome details of the subgroup of patients who did not receive an initial bolus of unfractionated heparin. If hemodynamic decompensation in the placebo group occurred primarily in this subgroup, the explanation may be a delayed onset of anticoagulant activity. Yvo Smulders, M.D.
Elevated Expression of Angiogenin in Prostate Cancer and Its Precursors

Purpose: Angiogenin is a polypeptide involved in the formation and establishment of new blood vessels necessary for growth and metastasis of numerous malignant neoplasms, including prostatic adenocarcinoma. Antiangiogenin therapy inhibits the establishment, growth, and metastasis of prostatic adenocarcinoma in animal studies. In this study, we have investigated the expression of angiogenin in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia, and adjacent benign prostatic epithelium in a large cohort of prostatectomy specimens. Methods: We have studied the expression of angiogenin by immunohistochemistry in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia, and adjacent benign prostatic tissue in 107 human total prostatectomy specimens. Results: The percentage of cells staining positively for angiogenin in benign prostatic glandular epithelium (mean = 17%) was significantly less than for high-grade prostatic intraepithelial neoplasia (mean = 58%, P < 0.001) and prostatic adenocarcinoma (mean = 60%, P < 0.001). Compared with adjacent benign prostatic epithelium, the staining intensity was significantly greater in high-grade prostatic intraepithelial neoplasia (P < 0.001) and prostatic adenocarcinoma (P < 0.001). Furthermore, staining intensity has significantly stronger in prostatic adenocarcinoma versus high-grade prostatic intraepithelial neoplasia (P = 0.0023). However, there was no correlation of angiogenin expression with various clinical and pathologic variables examined, including age at surgery, Gleason scores, pathologic stage, tumor extent, angiolymphatic invasion, extraprostatic extension, seminal vesical invasion, lymph node metastasis, surgical margin status, presence of prostatic intraepithelial neoplasia, and perineural invasion. Conclusion: Angiogenin expression in prostatic tissue increases as prostatic epithelial cells evolve from a benign to an invasive phenotype. The increasing expression of prostatic adenocarcinoma in the progression from benign prostate to high-grade prostatic intraepithelial neoplasia and ultimately to prostatic adenocarcinoma are consistent with previous studies showing the influential role that angiogenin plays in the growth, invasion, and metastasis of prostatic adenocarcinoma and many other malignant tumors.
Exact rate for convergence in probability of averaging processes via generalized min-cut

We study the asymptotic exponential decay rate I for the convergence in probability of products W<sub>k</sub>W<sub>k-1</sub>. W<sub>1</sub> of random symmetric, stochastic matrices W<sub>k</sub>. Albeit it is known that the probability P that the product W<sub>k</sub>W<sub>k-1</sub>. W<sub>1</sub> is ∈ away from its limit converges exponentially fast to zero, i.e., P ~ e<sup>-kI</sup>, the asymptotic rate I has not been computed before. In this paper, assuming the positive entries of Wk are bounded away from zero, we explicitly characterize the rate I and show that it is a function of the underlying graphs that support the positive (non zero) entries of W<sub>k</sub>. In particular, the rate I is given by a certain generalization of the min-cut problem. Although this min-cut problem is in general combinatorial, we show how to exactly compute I in polynomial time for the commonly used matrix models, gossip and link failure. Further, for a class of models for which I is difficult to compute, we give easily computable bounds: I ≤ I ≤ I̅, where I and I̅ differ by a constant ratio. Finally, we show the relevance of I as a system design metric with the example of optimal power allocation in consensus+innovations distributed detection.
Whole‐Cell Recording In Vivo

In vivo whole‐cell patch‐clamp recording provides a means for measuring membrane currents and potentials from individual cells in the intact animal. Patch‐clamp methods have largely been developed in vitro. This body of work has contributed enormously to the understanding of many important phenomena in excitable cells—including synaptic plasticity in the mammalian central nervous system, and the behavior of individual protein channels. In recent years, an increasing number of groups have applied whole‐cell recording techniques in the intact animal. Such in vivo studies offer the tantalizing possibility of uncovering the underlying principles and mechanisms of neural interactions within the natural context of fully intact biological networks. This unit focuses on strategies for overcoming the specific technical challenges posed by in vivo whole‐cell recording. A straightforward procedure is described for obtaining whole‐cell records from the cortex of the anesthetized rat; this procedure has also been applied successfully to awake animals and other rodent species with minor modifications.
Modelling of linear motor feed drives for grinding machines

This paper presents a dynamic model of linear motor feed drives for grinding machines. In this paper, analytical or empirical models for functionality-critical features of linear motor, including friction, grinding force and force ripple will be discussed. First, a dynamic friction model, based on the LuGre approach, will be used for the purpose of describing not only observed static but also dynamic friction phenomena, such as pre-sliding displacement, which is the prevailing friction phenomenon for high precision application. In order to study the influence of grinding force on linear motor feed drive positioning performance, an analytical grinding force model proposed by Hahn and Lindsay is employed. In addition to friction and grinding force, force ripple is taken into account, in view of its importance to machine tool applications, based on empirical modelling. To validate the force ripple model, the simulation result has been compared with the experimentally measured open-velocity response of a linear motor motion system. The effectiveness of the model has been shown by the agreement between the simulation and experimental results. The friction model has also been validated through the comparison of simulation results to experimentally measured response, obtained by frequency domain identification on an electro-mechanic motion system.
Sagittal Abdominal Diameter as a Surrogate Marker of Insulin Resistance in an Admixtured Population—Brazilian Metabolic Syndrome Study (BRAMS)

Background Sagittal abdominal diameter (SAD) has been proposed as a surrogate marker of insulin resistance (IR). However, the utilization of SAD requires specific validation for each ethnicity. We aimed to investigate the potential use of SAD, compared with classical anthropometrical parameters, as a surrogate marker of IR and to establish the cutoff values of SAD for screening for IR. Methods A multicenter population survey on metabolic disorders was conducted. A race-admixtured sample of 824 adult women was assessed. The anthropometric parameters included: BMI, waist circumference (WC), waist-to-hip ratio and SAD. IR was determined by a hyperglycemic clamp and the HOMA-IR index. Results After adjustments for age and total body fat mass, SAD (r = 0.23 and r = -0.70) and BMI (r = 0.20 and r = -0.71) were strongly correlated with the IR measured by the HOMA-IR index and the clamp, respectively (p < 0.001). In the ROC analysis, the optimal cutoff for SAD in women was 21.0 cm. The women with an increased SAD presented 3.2 (CI 95%: 2.1-5.0) more likelihood of having IR, assessed by the HOMA-IR index compared with those with normal SAD (p < 0.001); whereas women with elevated BMI and WC were 2.1 (95% CI: 1.4-3.3) and 2.8 (95% CI: 1.7-4.5) more likely to have IR (p < 0.001), respectively. No statistically significant results were found for waist-to-hip ratio. Conclusions SAD can be a suitable surrogate marker of IR. Understanding and applying routine and simplified methods is essential because IR is associated with an increased risk of obesity-related diseases even in the presence of normal weight, slight overweight, as well as in obesity. Further prospective analysis will need to verify SAD as a determinant of clinical outcomes, such as type 2 diabetes and cardiovascular events, in the Brazilian population.
ESTRADIOL 3-GLUCURONIDE IS TRANSPORTED BY THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 2 BUT DOES NOT ACTIVATE THE ALLOSTERIC SITE BOUND BY ESTRADIOL 17-GLUCURONIDE

β-Estradiol 17-(β-d-glucuronide) (E217G) is a well known cholestatic agent and substrate of multidrug resistance-associated protein 2 (Mrp2), whereas β-estradiol 3-(β-d-glucuronide) (E23G) is a noncholestatic regioisomer of E217G with unknown transport properties. The purpose of this study was to compare and contrast the Mrp2-mediated transport of E217G and E23G. The full coding region of rat Mrp2 was cloned into the baculovirus genome, the recombinant baculovirus used to infect Sf9 cells, and ATP-dependent transport of 3H-E23G and 3H-E217G in Sf9 cell membranes was characterized. Mrp2 transported E23G into an osmotically sensitive space, requiring ATP, with S50 = 55.7 μM, Vmax = 326 pmol·mg-1·min-1, and a Hill coefficient of 0.88. ATP-dependent Mrp2-mediated E217G transport was markedly stimulated at high E217G concentrations, consistent with positive cooperativity (Hill coefficient 1.5). E217G (5-125 μM) increased S50 but not Vmax for E23G transport, consistent with competitive inhibition. E23G (0.4-400 μM) completely, potently (IC50 = 14.2 μM), and competitively inhibited E217G transport, but E217G (0.01-250 μM) inhibited only 53% of E23G transport (IC50 = 33.4 μM). Estriol 16α-(β-d-glucuronide) potently and completely inhibited transport of E23G (IC50 = 2.23 μM), as did β-estradiol 3-sulfate 17-(β-d-glucuronide) (5-50 μM). In summary, E217G binds not only to an Mrp2 transport site, but also to an allosteric site that activates Mrp2 with positive cooperativity, thus activating its own transport and potentially that of other Mrp2 substrates, such as E23G. The noncholestatic E23G is an Mrp2 substrate and competes with E217G for transport, but does not activate the allosteric site.
The effect of stress on the defense systems

Acute stress increases resistance to infection. The alteration of this mechanism in chronically stressed people impairs the organism's ability to mount a strong immune response with a resultant increase in morbidity. Acute stress induces a probable sympatho–adrenergically mediated increase in chemotaxis and adhesion molecules expression, thus promoting immune cells migration to sites of infection and/or inflammation, while chronic stress impairs this mechanism. Protracted stressful conditions decrease NK cytotoxic capacity. There is a substance P, which under stressful circumstances mediates the increase in macrophage cytokine production. Acute stress increases T cell mobilization through a beta2–adrenergically mediated process, which is blunted during chronic stress. Psychological stress impairs the immune system's ability to produce antibodies in response to a vaccine, thereby making the organism more vulnerable to infections. Abbreviations: CRH = corticotrophin–releasing hormone; HPA = hypothalamic–pituitary–adrenocortical; IL = interleukin; NE = norepinephrine; NK = natural killer; SAM = sympathetic–adrenal medullary; S–IgA = secretory immunoglobulin A; SNS = sympathetic nervous system; TGF = transforming growth factor; Th = T helper; TNF = tumor necrosis factor
Everting suture correction of lower lid involutional entropion

AIMS To assess the long term efficacy of everting sutures in the correction of lower lid involutional entropion and to quantify the effect upon lower lid retractor function. METHODS A prospective single armed clinical trial of 62 eyelids in 57 patients undergoing everting suture correction of involutional entropion. Patients were assessed preoperatively and at 6, 12, 24, and 48 months postoperatively. The main outcome variables were lower lid position and the change in lower lid retractor function. RESULTS When compared with the non-entropic side, the entropic lid had a greater degree of horizontal laxity and poorer lower lid retractor function. These differences however, were not significant. At the conclusion of the study and after a mean follow up period of 31 months, the entropion had recurred in 15% of the patients. There were no treatment failures in the group of five patients with recurrent entropion. The improvement in lower lid retractor function after the insertion of lower lid everting sutures did not reach statistical significance. There was no significant difference between the treatment failure group and the group with a successful outcome with regard to: the degree of horizontal lid laxity or lower lid retractor function present preoperatively; patient age or sex; an earlier history of surgery for entropion. There was neither a demonstrable learning effect nor a significant intersurgeon difference in outcome. The overall 4 year mortality rate was 30%. CONCLUSIONS The use of everting sutures in the correction of primary or recurrent lower lid involutional entropion is a simple, successful, long lasting, and cost effective procedure.
A switched systems approach to vision-based tracking control of wheeled mobile robots

Conventional methods for image-based guidance, navigation, and control of a wheeled mobile robot (WMR) require continuous, uninterrupted state feedback at all times. However, tracked features may be lost due to occlusions or the trajectory of the WMR. In this paper, a set of dwell time conditions that can be used for trajectory design have been developed to relax the constant visibility constraint, while maintaining the ability to self-localize and track a desired trajectory. The use of a predictor for state estimates when landmark features are not visible helps to extend the time before image feedback of landmark features is required. Using Lyapunov-based switched systems analysis methods, maximum and minimum dwell time conditions are derived for periods when features are visible or not. A simulation is performed with a trajectory formed by Bézier splines to demonstrate a globally uniformly ultimately bounded trajectory tracking result despite intermittent measurements.
Some solution to the missing feature problem in data classification, with application to noise robust ASR

We address the theoretical and practical issues involved in automatic speech recognition (ASR) when some of the observation data for the target signal is masked by other signals. Techniques discussed range from simple missing data imputation to Bayesian optimal classification. We have developed the Bayesian approach because this allows prior knowledge to be incorporated naturally into the recognition process, thereby permitting us to go beyond the simple "integrate over missing data" or "marginals" approach reported elsewhere, which we show to be inadequate for dealing with realistic patterns of missing data. After deriving general techniques for recognition with missing data, these techniques are formulated in the context of an HMM based CSR system. This scheme is evaluated under both random and more realistic patterns of missing data, with speech from the DARPA RM corpus and noise from NOISEX. We find that a key problem in real world recognition with missing data is that efficient ASR requires data vector components to be independent, and incomplete data cannot be orthogonalised in the usual way by projection. We show that use of spectral peaks only can provide an effective solution to this problem.
Leiomyosarcoma of the Inferior Vena Cava

Leiomyosarcoma of the inferior vena cava (IVC) is a rare malignant vascular tumor, slow growing and often discovered late. Clinical presentation depends on the level of the IVC involved and diagnosis relies mostly on imaging methods. Two hundred and eighteen cases have been reported in the literature. The authors present the case of a 56-year-old man who underwent surgery for removal of a leiomyosarcoma of the medial caval segment. The procedure involved a radical excision with reconstruction of the IVC and reimplantation of the right renal vein. Clinical presentation, diagnosis and therapeutic modalities are discussed.
Roflumilast inhibits the release of chemokines and TNF‐α from human lung macrophages stimulated with lipopolysaccharide

BACKGROUND AND PURPOSE Lung macrophages are critically involved in respiratory diseases. This study assessed the effects of the PDE4 inhibitor roflumilast and its active metabolite, roflumilast N‐oxide on the release of a range of chemokines (CCL2, 3, 4, CXCL1, 8, 10) and of TNF‐α, from human lung macrophages, stimulated with bacterial lipopolysaccharide LPS.