Miracle-dz/UniFAR-FTUs huggingface dataset:
Growth hormone deficiency after treatment of acromegaly: a randomized, placebo-controlled study of growth hormone replacement.

CONTEXT The effects of GH replacement therapy in patients who develop GH deficiency (GHD) after cure of acromegaly have not been established in a placebo-controlled study. OBJECTIVE The objective of the study was to determine whether GH replacement improves body composition, cardiovascular risk markers and quality of life in patients with GHD and prior acromegaly. DESIGN This was a 6-month, randomized, placebo-controlled study. SETTING The study was conducted at a clinical translational science center. STUDY PARTICIPANTS Participants included 30 subjects with prior acromegaly and current GHD. INTERVENTION INTERVENTIONs included GH or placebo. MAIN OUTCOME MEASURES Body composition (dual-energy x-ray absorptiometry and cross-sectional computed tomography at L4), cardiovascular risk markers (high-sensitivity C-reactive protein (hsCRP), total, high-density lipoprotein and low-density lipoprotein cholesterol, fibrinogen, and carotid intimal-medial thickness), and quality of life were measured. RESULTS The mean GH dose at 6 months was 0.58 +/- 0.26 mg/d. Total fat mass, visceral adipose tissue (-15.3 +/- 18.6 vs. 1.3 +/- 12.5%, P = 0.01), and total abdominal fat decreased, and fat-free mass increased, in the GH vs. placebo group. Mean hsCRP levels decreased, but there was no GH effect on other cardiovascular risk markers. There was no change in glycosylated hemoglobin or homeostasis model assessment insulin resistance index. Quality of life improved with GH. Side effects were minimal. CONCLUSIONS This is the first randomized, placebo-controlled study of the effects of GH replacement therapy on body composition and cardiovascular end points in patients who have developed GH deficiency after treatment for acromegaly, a disease complicated by metabolic and body composition alterations and increased cardiovascular risk. GH replacement decreased visceral adipose tissue, increased fat-free mass, decreased hsCRP, and improved quality of life in patients with GHD after cure of acromegaly, with minimal side effects and without an increase in insulin resistance.
The calcemic response to continuous parathyroid hormone (PTH)(1-34) infusion in end-stage kidney disease varies according to bone turnover: a potential role for PTH(7-84).

CONTEXT Factors contributing to PTH resistance in dialysis patients remain elusive. OBJECTIVES The study assessed the skeletal and biochemical response to 46 h of PTH(1-34) infusion in dialysis patients. DESIGN The study was a prospective, controlled assessment of response to PTH(1-34). SETTING The study was performed at the University of California, Los Angeles, General Clinical Research Center. PARTICIPANTS Nineteen dialysis patients and 17 healthy volunteers were studied. INTERVENTION PTH(1-34) was infused at a rate of 8 pmol/kg x h for 46 h. Bone biopsy was performed in all dialysis patients. MAIN OUTCOME MEASURES Serum calcium, phosphorus, 1,25-dihydroxyvitamin D, PTH (four separate assays), and FGF-23 were determined at baseline and h 7, 23, 35, and 46 of the infusion. RESULTS Serum calcium levels rose in healthy volunteers (9.2 +/- 0.1 to 11.9 +/- 0.3 mg/dl; P < 0.01) and in dialysis patients with adynamic/normal bone turnover (9.0 +/- 0.3 to 10.7 +/- 0.7 mg/dl; P < 0.05) but did not change in dialysis patients with high bone turnover. Serum phosphorus levels declined in healthy volunteers (3.9 +/- 0.1 to 3.5 +/- 0.1 mg/dl; P < 0.05) but increased in all dialysis patients (6.7 +/- 0.4 to 8.0 +/- 0.3 mg/dl; P < 0.05). Full-length PTH(1-84) declined in all subjects; however, PTH(7-84) fragments declined only in healthy subjects and in dialysis patients with normal/adynamic bone but remained unchanged in dialysis patients with high bone turnover. CONCLUSIONS The skeleton of dialysis patients with high bone turnover is resistant to the calcemic actions of PTH. PTH(7-84) may contribute to this phenomenon.
Tetraiodothyroacetic acid (tetrac) and nanoparticulate tetrac arrest growth of medullary carcinoma of the thyroid.

CONTEXT Tetraiodothyroacetic acid (tetrac) blocks angiogenic and tumor cell proliferation actions of thyroid hormone initiated at the cell surface hormone receptor on integrin alphavbeta3. Tetrac also inhibits angiogenesis initiated by vascular endothelial growth factor and basic fibroblast growth factor. OBJECTIVE We tested antiangiogenic and antiproliferative efficacy of tetrac and tetrac nanoparticles (tetrac NP) against human medullary thyroid carcinoma (h-MTC) implants in the chick chorioallantoic membrane (CAM) and h-MTC xenografts in the nude mouse. DESIGN h-MTC cells were implanted in the CAM model (n = 8 per group); effects of tetrac and tetrac NP at 1 microg/CAM were determined on tumor angiogenesis and tumor growth after 8 d. h-MTC cells were also implanted sc in nude mice (n = 6 animals per group), and actions on established tumor growth of unmodified tetrac and tetrac NP ip were determined. RESULTS In the CAM, tetrac and tetrac NP inhibited tumor growth and tumor-associated angiogenesis. In the nude mouse xenograft model, established 450-500 mm(3) h-MTC tumors were reduced in size over 21 d by both tetrac formulations to less than the initial cell mass (100 mm(3)). Tumor tissue hemoglobin content of xenografts decreased by 66% over the course of administration of each drug. RNA microarray and quantitative real-time PCR of tumor cell mRNAs revealed that both tetrac formulations significantly induced antiangiogenic thrombospondin 1 and apoptosis activator gene expression. CONCLUSIONS Acting via a cell surface receptor, tetrac and tetrac NP inhibit growth of h-MTC cells and associated angiogenesis in CAM and mouse xenograft models.
Plasma fatty acids and desaturase activity are associated with circulating adiponectin in healthy adolescent girls.

CONTEXT Adiponectin can be a potential predictor of future metabolic derangements and some preliminary evidence supports the role of dietary fat in influencing adiponectin levels thus, the dietary determinants of adiponectin were investigated. OBJECTIVE The objective of the study was to evaluate the association of adiponectin concentrations with plasma fatty acids and indices of endogenous fatty acid metabolism. DESIGN This was a cross-sectional descriptive analysis to investigative the determinants of adiponectin. SETTING All subjects were examined at a large tertiary care center located in Montréal (Québec, Canada) between 2004 and 2006. SUBJECTS Subjects included 180 postpubertal, adolescent daughters (age range 13.6-17.3 yr) from a 15-yr retrospective cohort of mother-daughter pairs representing gestational diabetes mellitus affected (cases) and nonaffected (controls) pregnancies between 1989 and 1991. MAIN OUTCOME MEASURES Plasma adiponectin concentrations, plasma fatty acids presented grouped by series name and as individual fatty acids (reported as percent of total), and calculated indices of fatty acid metabolism were measured. RESULTS In linear regression analyses, adjusting for both waist circumference and insulin measured 2 h after the onset of an oral glucose tolerance test, the docosahexaenoic acid sufficiency index (an indicator of docosahexaenoic acid status) and alpha-linolenic acid (C18:3 n-3) were significantly negatively associated (P <or= 0.05) with adiponectin. After accounting for dietary fat intake, these associations disappeared, indicating an effect of diet. However, the long-chain saturated fatty acid, lignoceric (C24:0), was positively associated (P <or= 0.05) and Delta 9-18 desaturase activity (estimated from the ratio of 18:1 n-9/18:0) was significantly inversely (P <or= 0.01) associated with adiponectin concentrations. CONCLUSIONS Adiponectin, an inverse marker of metabolic derangements, was associated with desaturase activity, indicating that possible functional alterations in fatty acid metabolism may already be present in young healthy adolescent females.
Extremal Ranks of Some Symmetric Matrix Expressions with Applications

Suppose $A - BXB^*$, $A - BX - X^*B^*$, and $A - BX + X^*B^*$ are three linear matrix expressions over the field of complex numbers, where $A$ is an Hermitian or skew-Hermitian matrix. In this paper, we consider how to choose an Hermitian or skew-Hermitian matrix $X$ such that $A - BXB^*$ have the maximal and minimal possible ranks, and how to choose $X$ such that $A - BX \pm X^*B^*$ attain the minimal possible ranks. Some applications to Hermitian or skew-Hermitian solutions of matrix equations with symmetric patterns are also given.
Eigenvalue Problems in Fiber Optic Design

Maxwell's equation for modeling the guided waves in a circularly symmetric fiber leads to a family of partial differential equation-eigenvalue systems. Incorporating the boundary condition into a discretized system leads to an eigenvalue problem which is nonlinear in only one element. In fiber design one would like to determine the index profile which is involved in Maxwell's equation so that certain optical properties, which sometimes involve derivatives of the eigenvalues, are satisfied. This contribution discusses how to handle the nonlinear eigenvalue problem and how to determine derivatives of the eigenvalue problem.
Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer.

PURPOSE Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC. PATIENTS AND METHODS Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors. RESULTS The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4-87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies. CONCLUSIONS Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile.
The exon 3 deleted growth hormone receptor gene is associated with small birth size and early pubertal onset in healthy boys.

CONTEXT The GH/IGF-I axis influences gonadal development and function. Recently, a deletion of exon 3 in the GH receptor gene (GHRd3) has been linked to increased responsiveness to GH. OBJECTIVE Our objective was to evaluate the influence of the GHRd3 gene on birth size and pubertal onset. DESIGN AND SETTING We conducted a cross-sectional study, part of The COPENHAGEN Puberty Study, at a tertiary center for pediatric endocrinology. PARTICIPANTS Participants included 618 healthy boys aged 6.1-19.8 yr. MAIN OUTCOME MEASURES We assessed pubertal onset by genital staging and testicular palpation and parental reported birth weight and length. GHR genotypes were determined by multiplex PCR. RESULTS Age at onset of genital development (G2+) was significantly earlier in the GHRd3 homozygotes (GHRd3/d3) [10.86 (10.35-11.37) yr, mean (95% confidence interval)] compared with the full-length homozygotes (GHRfl/fl) [11.76 (11.35-12.00) yr, P = 0.002]. The odds ratio of having detectable testosterone levels for a given age was significantly higher in GHRd3/d3 compared with GHRfl/fl group (odds ratio = 3.1; 95% confidence interval = 1.2-8.9; P = 0.036). The GHRd3/d3 group the higher prepubertal IGF-I levels compared with the GHRfl/fl group (9.2% (0.1-18.1%), P = 0.048) after adjustment for IGF-binding protein-3 levels. Lower gestational-age-adjusted birth weight and length were found in the GHRd3/d3 group compared with the GHRfl/fl group and the GHRfl/d3 group, respectively (all P < or = 0.018). CONCLUSION The GHRd3/d3 genotype was associated with smaller birth size and earlier age at pubertal onset compared with the GHRfl/fl genotype. Thus, this common polymorphism could play a role for prenatal growth and gonadal development in boys.
Internalized somatostatin receptor subtype 2 in neuroendocrine tumors of octreotide-treated patients.

CONTEXT Somatostatin receptor subtype 2 (sst(2)) is widely expressed in neuroendocrine tumors and can be visualized immunohistochemically at the cell membrane for diagnostic purposes. Recently, it has been demonstrated in animal sst(2) tumor models in vivo that somatostatin analog treatment was able to induce a complete internalization of the tumor sst(2). PATIENTS AND METHODS In the present study, we evaluated whether sst(2) expressed in neuroendocrine tumors of patients treated with octreotide are also internalized. Tumor samples were assessed in patients that were treated with various octreotide modalities before and during surgery and compared with tumor samples from untreated patients. Sst(2) immunohistochemistry was performed in all samples with three different sst(2) antibodies (R2-88, UMB-1, and SS-800). Sst(2) receptor expression was confirmed by immunoblotting and in vitro receptor autoradiography. RESULTS Patients receiving a high dose of octreotide showed predominantly internalized sst(2), and patients with a low dose of octreotide had a variable ratio of internalized vs. membranous sst(2), whereas untreated patients had exclusively membranous sst(2). The internalized sst(2) receptor corresponded to a single sst(2) band in immunoblots and to sst(2) receptors in in vitro receptor autoradiography. Although generally found in endosome-like structures, internalized sst(2) receptors were also identified to a small extent in lysosomes, as seen in colocalization experiments. CONCLUSION It is the first evidence showing that sst(2) receptors can be internalized in sst(2)-expressing neuroendocrine tumors in patients under octreotide therapy, providing clues about sst(2) receptor biology and trafficking dynamics in patients.
Long‐term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy

Romiplostim was effective, safe, and well‐tolerated over 6–12 months of continuous treatment in Phase 3 trials in patients with immune thrombocytopenia (ITP). This report describes up to 5 years of weekly treatment with romiplostim in 292 adult ITP patients in a long‐term, single‐arm, open‐label study. Outcome measures included adverse events (including bleeding, thrombosis, malignancy, and reticulin/fibrosis), platelet response (platelet count >50 × 109 per litre), and the proportion of patients requiring rescue treatments. Treatment–related serious adverse events were infrequent and did not increase with longer treatment. No new classes of adverse events emerged. Thrombotic events occurred in 6·5% of patients and were not associated with platelet count. Median platelet counts of 50–200 × 109 per litre were maintained with stable doses of romiplostim (mean 5–8 μg/kg; generally self‐administered at home) throughout the study. A platelet response was achieved at least once by 95% of patients, with a platelet response maintained by all patients on a median 92% of study visits. There was a low rate of bleeding and infrequent need for rescue treatments. In conclusion, this study demonstrated that romiplostim was safe and well‐tolerated over 614 patient‐years of exposure in ITP patients, and that efficacy was maintained with stable dosing for up to 5 years of continuous treatment.
Rise of oxyntomodulin in response to oral glucose after gastric bypass surgery in patients with type 2 diabetes.

CONTEXT The mechanisms by which Roux-en-Y gastric bypass surgery (GBP) results in sustained weight loss and remission of type 2 diabetes are not fully understood. OBJECTIVE We hypothesized that the anorexic hormone oxyntomodulin (OXM) might contribute to the marked weight reduction and the rapid improvement in glucose metabolism observed in morbidly obese diabetic patients after GBP. METHODS Twenty obese women with type 2 diabetes were studied before and 1 month after GBP (n=10) or after a diet-induced equivalent weight loss (n=10). Patients from both groups were matched for age, body weight, body mass index, and diabetes duration and control. OXM concentrations were measured during a 50-g oral glucose challenge before and after weight loss. RESULTS At baseline, OXM levels (fasting and stimulated values) were indistinguishable between the GBP and the diet group. However, OXM levels rose remarkably in response to an oral glucose load more than 2-fold (peak, 5.25+/-1.31 to13.8+/-16.2 pmol/liter; P=0.025) after GBP but not after diet. The peak of OXM after glucose was significantly correlated with glucagon-like peptide-1 and peptide YY3-36. CONCLUSIONS Our data suggest that the observed changes in OXM primarily occur in response to GBP and not as a consequence of weight loss. These changes were observed early after surgery and occurred in parallel with previously reported increases in incretins and peptide YY. We speculate that the combination of gut hormone changes is essential for the improved glucose homeostasis and may partially explain the success of this surgery on diabetes resolution and weight loss.
Conditioning and Padé Approximation of the Logarithm of a Matrix

In this work we (i) use the theory of piecewise analytic functions to represent the Frechet derivative of any primary matrix function, in particular of primary logarithms; (ii) propose an indicator to assess inherent difficulties to compute a logarithm; and (iii) revisit Pade approximation techniques for the principal logarithm of block triangular matrices.
Midwifery diagnosis of labour onset

The premise of this study was that midwifery diagnostic cues have been subsumed by the biomedical approach. The purpose of this qualitative study was to find out how midwives diagnose labour onset and create a model of that knowledge. Two approaches for data collection were used: A preliminary midwife focus group and a series of in-depth interviews with an expert midwife. The focus group generated themes and concepts leading to a three part conceptual framework: physiological, sociophilosophical and psychological. The main findings were that midwives use a variety of emotional, psychological and physical cues to diagnose labour onset. The overall ‘tendency’ for labour onset is described as ‘increasing inward focus’, reflected in cues such as movements, breathing, conversation and emotional states. The recognition and use of these cues is influenced by the political and social context in which a midwife works. The final model demonstrates how midwives can work with women outside the biomedical paradigm. It is hoped that this research will contribute to a midwifery discourse surrounding labour onset care.
On PreemptiveResource Constrained Scheduling: Polynomial-Time Approximation Schemes

We study resource constrained scheduling problems where the objective is to compute feasible preemptive schedules minimizing the makespan and using no more resources than what are available. We present approximation schemes along with some inapproximability results showing how the approximability of the problem changes in terms of the number of resources. The results are based on linear programming formulations (though with exponentially many variables) and some interesting connections between resource constrained scheduling and (multidimensional, multiple-choice, and cardinality constrained) variants of the classical knapsack problem. In order to prove the results we generalize a method by Grigoriadis et al. for the max-min resource sharing problem to the case with weak approximate block solvers (i.e., with only constant, logarithmic, or even worse approximation ratios). Finally, we present applications of the above results in fractional graph coloring and multiprocessor task scheduling.
The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp.

CONTEXT To meet the worldwide challenge of emerging diabetes, accessible and inexpensive tests to identify insulin resistance are needed. OBJECTIVE To evaluate the sensitivity and specificity of the product of fasting, we compared the triglycerides and glucose (TyG) index, a simple measure of insulin resistance, with the euglycemic-hyperinsulinemic clamp test. DESIGN AND SETTING We conducted a cross-sectional study of the general population and outpatients of the Internal Medicine Department at the Medical Unit of High Specialty of the Specialty Hospital at the West National Medical Center in Guadalajara, Mexico. PATIENTS Eleven nonobese healthy subjects, 34 obese normal glucose tolerance individuals, 22 subjects with prediabetes, and 32 diabetic patients participated in the study. INTERVENTION We performed a euglycemic-hyperinsulinemic clamp test. MAIN OUTCOME MEASURES Sensitivity and specificity of the TyG index [Ln(fasting triglycerides) (mg/dl) x fasting glucose (mg/dl)/2] were measured, as well as the area under the curve of the receiver operating characteristic scatter plot and the correlation between the TyG index and the total glucose metabolism (M) rates. RESULTS Pearson's correlation coefficient between the TyG index and M rates was -0.681 (P < 0.005). Correlation between the TyG index and M rates was similar between men (-0.740) and women (-0.730), nonobese (-0.705) and obese (-0.710), and nondiabetic (-0.670) and diabetic (-0.690) individuals. The best value of the TyG index for diagnosis of insulin resistance was 4.68, which showed the highest sensitivity (96.5%) and specificity (85.0%; area under the curve + 0.858). CONCLUSIONS The TyG index has high sensitivity and specificity, suggesting that it could be useful for identification of subjects with decreased insulin sensitivity.