Miracle-dz/UniFAR-FTUs huggingface dataset:
Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids

AbstractThe incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5 × 1.5-cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1&agr;, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5-, and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively.The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No optimal treatment for such metastases has yet been defined.
Serum zinc-alpha2-glycoprotein correlates with adiposity, triglycerides, and the key components of the metabolic syndrome in Chinese subjects.

CONTEXT Zinc-alpha2-glycoprotein (ZAG) is a 40-kDa circulating glycoprotein secreted from the liver and adipose tissues. Animal studies have demonstrated the role of ZAG as a lipid-mobilizing factor involved in regulating lipid metabolism and adiposity. However, the clinical relevance of these findings remains to be established. OBJECTIVE This study aimed to address the relationship of serum ZAG levels with adiposity and cardiometabolic risk factors in humans. DESIGN AND SETTING A total of 258 Chinese subjects [aged 55.1 +/- 12.5 yr; 120 males, 138 females; body mass index (BMI), 25.4 +/- 4.1 kg/m(2)] were randomly selected from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study, based on their BMI. Serum ZAG levels were determined with ELISA. The relationship between serum ZAG levels and cardiometabolic parameters was assessed. RESULTS Serum ZAG levels were higher in men (P < 0.001 vs. women). Serum ZAG correlated positively with age, parameters of adiposity (waist circumference and BMI), fasting insulin, insulin resistance indices, serum triglycerides, adipocyte-fatty acid-binding protein, and C-reactive protein, and diastolic blood pressure (all P < 0.005, age- and sex-adjusted), and inversely with high-density lipoprotein-cholesterol levels (P = 0.008, age- and sex-adjusted). It was also elevated progressively with an increasing number of components of the metabolic syndrome (P for trend < 0.001). On multivariate analysis, serum ZAG was independently associated with male sex, the metabolic syndrome (or type 2 diabetes and serum triglycerides), and C-reactive protein (all P <or= 0.002). CONCLUSIONS ZAG might be involved in the pathogenesis of obesity-related metabolic disorders in humans and thus warrants further investigation.
Serum 25-Hydroxyvitamin D Levels Are Strongly Related to Systolic Blood Pressure But Do Not Predict Future Hypertension

Vitamin D receptors have been detected in vascular smooth muscle cells, and 1,25-dihydroxyvitamin D inhibits the renin mRNA expression. Epidemiological studies show an inverse relation between serum 25-hydoxyvitamin D levels and blood pressure, and low serum 25-hydoxyvitamin D levels are reported to be predictors of future development of hypertension. This may indicate an important role for vitamin D in blood pressure regulation. In the present study, 25-hydoxyvitamin D was measured in sera collected in 1994 from 4125 subjects who did not use blood pressure medication, and thereafter measurement was repeated in 2008 for 2385 of these subjects. In sera from 1994 there was a significant decrease in age, body mass index, and systolic blood pressure and a significant increase in physical activity score across increasing 25-hydoxyvitamin D quartiles. After adjusting for sex, age, body mass index, and physical activity, the difference in systolic blood pressure between the lowest and highest serum 25-hydoxyvitamin D quartiles was 3.6 mm Hg. After adjustment for confounders, serum 25-hydoxyvitamin D from 1994 did not predict future hypertension or increase in blood pressure, nor was there any significant association between change in serum 25-hydoxyvitamin D from 1994 to 2008 and change in blood pressure. Our results do not support a causal role for vitamin D in blood pressure regulation, and large randomized clinical trials, preferably including subjects with hypertension and/or low serum 25-hydoxyvitamin D levels, are greatly needed to clarify whether vitamin D supplementation affects the blood pressure.
A Systematic Review of Stenting and Angioplasty of Symptomatic Extracranial Vertebral Artery Stenosis

Background and Purpose— Extracranial vertebral artery stenosis (ECVAS) is common among patients with ischemic stroke. Despite the limited knowledge of the natural history of patients with symptomatic vertebral disease, endovascular revascularization techniques are now utilized in clinical practice. We sought to determine the risk of endovascular treatment for ECVAS with a systematic review of the literature. Methods— A search strategy was used using the terms “stenting,” “vertebral,” “ostium,” “origin,” and “extracranial” through Medline. All articles were reviewed along with their references to determine the risk and durability of endovascular treatment. Results— A total of 27 articles were identified that met inclusion criterion, with a total of 980 of 993 patients treated with stents. The majority of patients (56%) were noted to have contralateral vertebral artery stenosis or occlusion and 92% were symptomatic at the time of treatment. A total of 11 patients (1.1%) experienced a stroke and 8 (0.8%) experienced a transient ischemic attack within 30 days of the procedure. Drug-eluting stents were associated with lower restenosis rates (11%) compared to bare metal stents (30%) at a mean of 24 months of follow-up. Conclusions— Stenting and angioplasty of ECVAS appear to have a low rate of periprocedural stroke or transient ischemic attack and restenosis rates that may not be as high as suspected. Given the frequency of ECVAS as an etiology for ischemic stroke, future studies aimed at determining efficacy of this treatment modality relative to medical therapy would be of benefit to clinicians caring for these patients.
THE EXCHANGE FORMULA FOR DISTRIBUTIONS AND SPANS OF TRANSLATES

1. The aims of this paper are modest. Let Rm denote real Euclidean space of m dimensions with points x = (xi, * * *, Xm); we look upon Rm as an additive locally compact abelian group whose dual is isomorphic with Rm. We reserve the notation y = (yr, * * *, yi) for points of Rm when regarded as elements of the dual. Concerning distributions on Rm, we adopt the notation of Schwartz [1]. In the theory of the generalised Fourier transform there are two basic "exchange formulae" [1, vol. 2, p. 124] in which are specified mutual relationships between two temperate distributions u and v with transforms U and V in order that either or both of the relations
Substance use among runaway and homeless youth in three national samples.

OBJECTIVES Standardized estimates of the prevalence of substance use by runaway and homeless youth between the ages of 12 and 21 in various settings were compared with each other and with estimates for youth in the general population. METHODS Four surveys were used: (1) a nationally representative survey of runaway and homeless youth residing in federally and non-federally funded shelters; (2) a multicity survey of street youth; (3) a nationally representative household survey of youth with and without recent runaway and homeless experiences; and (4) a nationally representative household survey of youth whose previous runaway/homeless status was unknown. RESULTS For almost every substance, substance use prevalence was highest among street youth. Shelter youth and household youth with recent runaway/homeless experiences reported similar rates. In the household surveys, substance use rates were lowest and were generally comparable. CONCLUSIONS Many homeless and runaway youth use tobacco, alcohol, and other drugs at rates substantially higher than nonrunaway and nonhomeless youth, indicating a need for comprehensive and intensive substance abuse prevention and treatment services for these youth.
Management of cancer pain: ESMO Clinical Practice Guidelines.

C. I. Ripamonti1, D. Santini2, E. Maranzano3, M. Berti4 & F. Roila5, on behalf of the ESMO Guidelines Working Group* Supportive Care in Cancer Unit, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy; Oncologia Medica, Università Campus Bio-Medico, Rome, Italy; Department of Oncology, Radiation Oncology Centre, S. Maria Hospital, Terni, Italy; Anaesthesiology Intensive Care and Pain Therapy, University Hospital Parma, Parma, Italy; Department of Medical Oncology, S. Maria Hospital, Terni, Italy
The 5' nontranslated region of hepatitis A virus RNA: secondary structure and elements required for translation in vitro

Although the lengthy 5' nontranslated regions (5'NTRs) of other picornaviral RNAs form highly ordered structures with important functions in viral translation, little is known about the 5'NTR of hepatitis A virus (HAV). We determined the nearly complete 5'NTR nucleotide sequences of two genetically divergent HAV strains (PA21 and CF53) and included these data in a comparative phylogenetic analysis of the HAV 5'NTR. We identified covariant nucleotide substitutions predictive of conserved secondary structures and used this information to develop a model of the 5'NTR secondary structure, which was further refined by thermodynamic predictions and nuclease digestion experiments. According to this model, the 5'NTR comprises six major structural domains. Domains I and II (bases 1 to 95) contain a 5'-terminal hairpin and two stem-loops followed by a single-stranded and highly variable pyrimidine-rich tract (bases 96 to 154). The remainder of the 5'NTR (domains III to VI, bases 155 to 734) contains several complex stem-loops, one of which may form a pseudoknot, and terminates in a highly conserved region containing an oligopyrimidine tract preceding the putative start codon by 13 bases. To determine which structural elements might function as an internal ribosome entry site, RNA transcripts representing the HAV 5'NTR with progressive 5' deletions were translated in rabbit reticulocyte lysates. The translation product was truncated, unprocessed P1 polyprotein. Removal of the 5'-terminal 354 bases of the 5'NTR had little effect on translation. However, deletion to base 447 slightly decreased translation, while deletion to base 533 almost completely abolished it. These data indicate that sequences 3' of base 355 play an important role in the translation mechanism utilized by genomic-length HAV RNA. Significantly, this region shares several conserved structural features with the internal ribosome entry site element of murine encephalomyocarditis virus.
Outcomes of Endoscopic Submucosal Dissection Versus Endoscopic Mucosal Resection in Management of Superficial Squamous Esophageal Neoplasms Outside Japan

Goals This study aims to evaluate the outcomes of endoscopic submucosal dissection (ESD) versus endoscopic mucosal resection (EMR) in management of superficial squamous esophageal neoplasms. Background Endoscopic resection is a potential alternative in treatment of superficial squamous esophageal neoplasms. However, there have been limited reports comparing the outcomes of ESD versus EMR in the treatment of these lesions outside Japan. Study A retrospective analysis of all patients with high-grade superficial neoplasms (moderate to severe dysplasia and noninvasive carcinoma) or intramucosal carcinoma resected endoscopically between January 2002 and December 2007 was carried out. Clinical and pathologic outcomes were compared. Results ESD was done in 22 lesions (18 patients) and cap-EMR in 13 lesions (10 patients). ESD allowed resection of larger lesions indicated by a significantly longer endoscopic length (P=0.015), larger specimen size (P<0.001), and more lesions extending for more than half the circumference of the esophagus (P=0.005) when compared with cap-EMR. ESD also achieved with a higher en bloc resection rate (P=0.052) and lower piecemeal resection rate (P=0.015). Procedure-related morbidities were not significantly different (P=1.0). There was no procedure-related mortality in the entire series. Conclusions ESD allows en bloc resection of larger mucosal lesions of the esophagus, earlier not possible by cap-EMR. This is achievable without significantly increasing the risks to the patient even in low-volume centers outside Japan. Whether ESD decreases the local recurrence and improves survival when compared with cap-EMR will require further long-term follow-up studies.
Selective laser sintering of Mo-CuNi composite to be used as EDM electrode

Purpose – This work is focused on the investigation of direct production of electrical discharge machining (EDM) electrodes through the selective laser sintering (SLS) technique using a new metal-matrix composite material made of molybdenum and a copper-nickel alloy (Mo-CuNi). The influence and optimization of the main SLS parameters on the densification behavior and porosity is experimentally studied. Additionally, EDM experiments are performed to evaluate the electrodes performance under different machining conditions. The paper aims to discuss these issues. Design/methodology/approach – The new EDM electrode material used was a powder system composed of Mo and pre-alloyed CuNi. A systematic experimental methodology was designed to evaluate the effects of layer thickness, laser scan speed and hatch distance. The densification behavior, porosity and surface morphology of the samples were analyzed through microstructural and surface analysis. EDM experiments were conducted under three different regimes in.
CALR mutations are rare in childhood essential thrombocythemia

To the Editor: The incidence of childhood myeloproliferative neoplasms is significantly lower than that in adults. Also, the common JAK2 V617F mutation and other MPN-associated mutations are detected less frequently [1] inferring differences in both the etiology and molecular pathogenesis of these diseases in adults and children. Two recent reports have identified acquired insertion/deletion mutations of CALR, exclusively in exon 9, in approximately 70–80% of adult essential thrombocythemia (ET) and primary myelofibrosis (PMF) that do not possess JAK2 orMPL mutations by exome sequencing approaches. Furthermore they have demonstrated a previously unrecognized molecular complexity to these malignancies [2,3]. These two studies prompted the investigation of CALR mutations in pediatric MPN. The presence of CALR exon 9 mutations was retrospectively investigated using fluorescent PCR fragment analysis [2] in the blood or bone marrow DNA from a relatively small single-center cohort of unrelated, sporadic pediatric MPN classified according to established hematological, histo-morphological and molecular criteria [4]. This comprised of JAK2 V617F-negative ET (n1⁄4 4), JAK2 V617F-positive ET (n1⁄4 2) (Table I), JAK2 V617F-positive polycythemia vera (PV; n1⁄4 1), JAK2 V617F-negative polycythemia (n1⁄4 2), and reactive thrombocytosis (n1⁄4 8). All MPN patients had noMPLW515L or W515Kmutations. Two different mutations found in adult MPN acted as positive controls. CALR mutations were not detected in the four JAK2 V617F-negative ET patients. Also, no CALR mutations were detected in three JAK2 V617Fpositive MPN patients or in the eight children with reactive thrombocytosis (Table I). While this brief study demonstrates absence of CALR exon 9 mutations in JAK2V617F-positive childhood MPN, no CALR exon 9 mutations were found in the four JAK2 V617F-negative children with ET. If the molecular pathogenesis of pediatric and adult MPN was similar then one might expect to detect CALR mutations in a certain proportion of young JAK2and MPL-negative ET patients. Whether CALR mutations are present and will have a role in the diagnosis and classification of childhoodMPN requires verification in a larger cohort. This study serves to highlight another potential biological difference between childhood and adult MPN.
Difference-differential equations for fluid flow in distensible tubes.

The solution by Womersley of the Navier-Stokes equations for fluid flow in distensible tubes has been most useful to students of hemodynamics. However, this solution requires linearization, and, because results are obtained after transformation into the frequency domain, nonlinear or time-varying effects are not easily added. Analog, hybrid, or digital computer simulation require that difference-differential equations be obtained. This proves to be readily possible by returning to the Navier-Stokes and continuity equations, and using ordinary difference techniques in the space dimensions.
Amyloid-β Aggregates Cause Alterations of Astrocytic Metabolic Phenotype: Impact on Neuronal Viability

Amyloid-β (Aβ) peptides play a key role in the pathogenesis of Alzheimer's disease and exert various toxic effects on neurons; however, relatively little is known about their influence on glial cells. Astrocytes play a pivotal role in brain homeostasis, contributing to the regulation of local energy metabolism and oxidative stress defense, two aspects of importance for neuronal viability and function. In the present study, we explored the effects of Aβ peptides on glucose metabolism in cultured astrocytes. Following Aβ25-35 exposure, we observed an increase in glucose uptake and its various metabolic fates, i.e., glycolysis (coupled to lactate release), tricarboxylic acid cycle, pentose phosphate pathway, and incorporation into glycogen. Aβ increased hydrogen peroxide production as well as glutathione release into the extracellular space without affecting intracellular glutathione content. A causal link between the effects of Aβ on glucose metabolism and its aggregation and internalization into astrocytes through binding to members of the class A scavenger receptor family could be demonstrated. Using astrocyte-neuron cocultures, we observed that the overall modifications of astrocyte metabolism induced by Aβ impair neuronal viability. The effects of the Aβ25-35 fragment were reproduced by Aβ1-42 but not by Aβ1-40. Finally, the phosphoinositide 3-kinase (PI3-kinase) pathway appears to be crucial in these events since both the changes in glucose utilization and the decrease in neuronal viability are prevented by LY294002, a PI3-kinase inhibitor. This set of observations indicates that Aβ aggregation and internalization into astrocytes profoundly alter their metabolic phenotype with deleterious consequences for neuronal viability.
Is drug-resistant Mycobacterium leprae a real cause for concern?: First approach to molecular monitoring of multibacillary Colombian patients with and without previous leprosy treatment.

INTRODUCTION There is no information in Colombia on Mycobacterium leprae primary and secondary drug resistance in regards to the WHO-multidrug therapy regime. On the other hand, public health authorities around the world have issued various recommendations, one of which prompts for the immediate organization of resistance surveillance through simple molecular methods. OBJECTIVE To determine the prevalence of Mycobacterium leprae drug resistance to rifampicin, ofloxacin and dapsone in untreated and previously treated patients at the Centro Dermatológico Federico Lleras Acosta during the 1985-2004 period. MATERIALS AND METHODS We conducted a retrospective study which included multibacillary patient biopsies through elective sampling: 381 of them from new patients and 560 from previously treated patients. Using a microtome, we obtained six slides from each skin biopsy preserved in paraffin, and we extracted M. leprae DNA. We amplified three molecular targets through PCR and obtained the patterns of drug resistance to dapsone, rifampicin and ofloxacin by reverse hybridization. Finally, we collected epidemiological, clinical and demographical data for analyses. RESULTS From 941 samples under study, 4.14% of them were resistant to one or more drugs, and 5.77 and 3.04% had resistant genotypes in new and previously treated patients, respectively. Total resistance for each drug was 0.43% for dapsone, 3.19% for rifampicin and 1.17% for ofloxacin. We found statistically significant differences for rifampicin and for the total population when comparing the results from untreated versus previously treated patients. Two thirds of the resistant samples were resistant to rifampicin alone or combined. CONCLUSIONS The standard multidrug therapy schemes continue being effective for leprosy cases; however, it is necessary to guarantee adherence and regularity. Surveillance to drug resistance in new and previously treated leprosy cases should be established.
Longer duration of cardiopulmonary bypass is associated with greater numbers of cerebral microemboli.

BACKGROUND AND PURPOSE Many patients who undergo cardiac surgery assisted with cardiopulmonary bypass (CPB) experience cerebral injury, and microemboli are thought to play a role. Because an increased duration of CPB is associated with an increased risk of subsequent cerebral dysfunction, we investigated whether cerebral microemboli were also more numerous with a longer duration of CPB. METHODS Brain specimens were obtained from 36 patients who died within 3 weeks after CPB. Specimens were embedded in celloidin, sectioned 100 microm thick, and stained for endogenous alkaline phosphatase, which outlines arterioles and capillaries. In such preparations, emboli can be seen as swellings in the vessels. Cerebral microemboli were counted in equal areas and scored as small, medium, or large to estimate the embolic load (volume of emboli). RESULTS With increasing survival time after CPB, the embolic load declined (P<0.0001). (Lipid emboli are known to pump slowly through the brain.) Also with increasing time after CPB, the percentage of large and medium emboli became lower (P=0.0034). This decline is consistent with the concept that the emboli break into smaller globules as they pass through the capillary network. A longer duration of CPB was associated with increased embolic load (P=0. 0026). For each 1-hour increase in the duration of CPB, the embolic load increased by 90.5%. CONCLUSIONS Thousands of microemboli were found in the brains of patients soon after CPB, and an increasing duration of CPB was associated with an increasing embolic load.